Showing papers in "Neuroscience and Behavioral Physiology in 2017"
TL;DR: A review of studies of the use of melatonin in fibromyalgia, headaches, irritable bowel syndrome, chronic back pain, and rheumatoid arthritis shows that melatonin has independent analgesic influences mediated via melatonin receptors and various neurotransmitter systems.
Abstract: Melatonin is a neurohormone synthesized in the pineal gland and extrapineal structures and has a number of functions, including chronobiotic, antioxidant, oncostatic, immunomodulatory, normothymic, and anxiolytic actions, the abilities to affect the cardiovascular system and the gastrointestinal tract and take part in reproductive functions, and a role in regulating substance metabolism and body weight. In addition, recent studies have demonstrated the efficacy of melatonin in relation to pain syndromes. We present here a review of studies of the use of melatonin in fibromyalgia, headaches, irritable bowel syndrome, chronic back pain, and rheumatoid arthritis. The possible mechanisms mediating the analgesic properties of melatonin are discussed. On the one hand, normalization of circadian rhythms, which are inevitably deranged by chronic pain syndromes, improves sleep and activates the intrinsic adaptive potential of melatonin; on the other, data have been obtained showing that melatonin has independent analgesic influences mediated via melatonin receptors and various neurotransmitter systems.
32 citations
TL;DR: This review of the literature and the own data analyzes the relationship between anxiety and depression and concludes that existing antidepressants and anxiolytics exert their therapeutic effects even in the monopolar development of anxiety or depression in only a limited number of cases.
Abstract: The symptoms of depression and anxiety often accompany each other. This is apparent both in clinical practice and in laboratory studies. The combination of anxiety and depression in humans responds more slowly to treatment, requires higher doses of drugs, and increases the probability of suicide and the frequency of recurrences. In addition, existing antidepressants and anxiolytics exert their therapeutic effects even in the monopolar development of anxiety or depression in only a limited number of cases. This review of the literature and our own data analyzes the relationship between anxiety and depression. Psychotropic drugs with different spectra of action in a model of mixed anxiety/depression disorder induced by chronic social stress in male mice showed that the states of anxiety and depression change independently in response to anxiolytics and antidepressants.
23 citations
TL;DR: The aim of the present literature review was to summarize the data accumulated on the likely pathogenetic mechanisms of neuron loss in Alzheimer's disease.
Abstract: One of the main elements in the pathogenesis of Alzheimer’s disease consists of larger decreases in the numbers of neurons in various parts of the brain than seen in normal ageing. The relevance of studying the pathogenesis of this process arises from the fact that neuron loss starts at the early, preclinical stage of Alzheimer’s disease, when amyloid plaques and neurofibrillary tangles (the main morphological signs of the disease) have still not formed; neuron loss correlates with the extent of clinical signs of the disease. Data have now accumulated on the likely pathogenetic mechanisms of neuron loss. The aim of the present literature review was to summarize these data.
20 citations
TL;DR: This review considers the key points in BDNF expression and its proteolysis to BDNF, as well as the role of brain-derived neurotrophic factor in the developing nervous system, in the processes of long-term synaptic plasticity, memory consolidation and extinction, and possible involvement in the development of various nervous system pathologies.
Abstract: Brain-derived neurotrophic factor (BDNF) is one of the most widely distributed protein regulators of many biological processes in the central nervous system. Like other neurotrophins, BDNF is synthesized in cells as a precursor molecule (proBDNF), which undergoes proteolytic cleavage to form the mature form, BDNF. The effectiveness of proteolysis of the proform and, thus, the proBDNF/BDNF ratio, has been shown to be determined by the nature of concomitant neuronal activity. Extensive data have provided evidence that the BDNF precursor (proBDNF) has intrinsic biological functions, which are often diametrically opposed to the functions of the mature neurotrophin. Thus, the proBDNF/BDNF balance is an important component in the regulation of many process in central nervous system cells. This review considers the key points in BDNF expression and its proteolysis to BDNF, as well as the role of brain-derived neurotrophic factor in the developing nervous system, in the processes of long-term synaptic plasticity, memory consolidation and extinction, and possible involvement in the development of various nervous system pathologies.
17 citations
TL;DR: Recent developed approaches to restoring the functions of the melanocortin signal system are discussed as one pathway to the treatment and prophylaxis of type 2 diabetes mellitus and metabolic syndrome.
Abstract: Changes in the functional activity of the melanocortin signal system of the hypothalamus, which is involved in regulating feeding behavior and peripheral homeostasis, play an important role in the etiology and pathogenesis of type 2 diabetes mellitus and metabolic syndrome This review discusses current concepts of the structural-functional organization of the melanocortin signal system and its interactions with other hypothalamic signal systems Data on impairments to melanocortin signal cascades in hypothalamic neurons are presented – these may be the primary causes of type 2 diabetes mellitus and metabolic syndrome or the result of hormonal changes arising in the conditions of these metabolic disorders Recently developed approaches to restoring the functions of the melanocortin signal system are discussed as one pathway to the treatment and prophylaxis of type 2 diabetes mellitus and metabolic syndrome
8 citations
TL;DR: Baclofen did not show any significant difference from placebo in terms of the number of side effects (adverse events) and effects on liver enzyme activity, which is evidence for its good tolerance and safety in this contingent of patients.
Abstract: Objective. To study the efficacy and use of baclofen (Baclosan) for stabilizing remission in patients with alcoholism. Materials and methods. A total of 32 patients with alcoholism were randomized to two groups. Patients of group 1 (16 patients) received baclofen (50 mg/day) for three months; patients of group 2 received a placebo of identical appearance. All patients were required to attend the clinic every week for monitoring of remission (alcohol consumption) and assessment of the levels of alcohol attraction (craving), affective disorders (depression and anxiety), and γ-glutamyltransferase (GGT) activity, and for monitoring of compliance with medication (urine riboflavin). Alcohol consumption was monitored by retrospective analysis and assay of GGT. Anxiety was evaluated using the Hamilton and Spielberger scales. Depression was assessed on the Montgomery-Asberg Depression Scale. Alcohol cravings were assessed using obsessive-compulsive, Pennsylvania, and visual analog scales. Overall assessment of treatment efficacy was obtained using the Clinical Global Impression scale. The study followed a double-blind design. Results and conclusions. No significant difference in measures of the efficacy of stabilizing remission was seen between the baclofen and placebo groups in patients with alcoholism (probably due to insufficiently large cohort sizes). Measures of holding patients in remission and of alcohol consumption in the baclofen group were somewhat better than in the placebo group; between-group differences in these measures approached statistical significance, pointing to a greater efficacy for baclofen than placebo in alcoholism. Baclofen did not show any significant difference from placebo in terms of the number of side effects (adverse events) and effects on liver enzyme activity, which is evidence for its good tolerance and safety in this contingent of patients. The authors take the view that evidence-based conclusions regarding The efficacy of baclofen in the treatment of alcoholism require further studies in patients using larger cohorts.
8 citations
TL;DR: The role of autophagy in supporting cellular survival and inhibiting neurodegeneration in Alzheimer's disease, Parkinson's disease and Huntington's disease is discussed in this paper, which are accompanied by the accumulation of the proteins β-amyloid, α-synuclein, and huntingtin.
Abstract: The role of autophagy in supporting cellular survival and inhibiting neurodegeneration in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, which are accompanied by the accumulation of the proteins β-amyloid, α-synuclein, and huntingtin, is discussed. Autophagy undergoes various degrees of weakening in these diseases, and also decreases in aging. Removal of accumulated toxic proteins and structures is mediated by the mechanisms of autophagy (chaperone-mediated autophagy, macroautophagy, mitophagy) in interactions with the ubiquitin-proteasome system. In many cases, activation of mTOR-dependent autophagy and mTOR-independent pathways for its regulation leads to the therapeutic effect of inhibiting neurodegeneration in cell cultures and animal models of diseases. A number of autophagy activators (resveratrol, metformin, rilmenidine, lithium, cucurmin, etc.) are in the stage of clinical trials.
7 citations
TL;DR: Antenatal alcoholization in rats induced various histological changes in the frontal cortex, which were long-lasting and progressive during postnatal ontogeny.
Abstract: The aim of the present work was to undertake a comparative study of the effects of prenatal alcoholization of the histological characteristics of neurons in the frontal cortex of the brains of rats of different ages. Experiments were performed on 175 mongrel white rats – the offspring of 25 females given 15% ethanol as drinking solution throughout pregnancy. The cerebral cortex was studied on postnatal days 2–90 using histological, histochemical, and morphometric methods. An increase (on days 2 and 5) followed by a decrease (on days 10 and 90) was seen in cortical thickness, with a decrease in neuron body size (on days 20–90), a decrease in the number of neurons in cortical layer V, a decrease in the number of normochromic cells, and increases in the numbers of hyperchromic shrunken neurons and ghost cells throughout the study period. Antenatal alcoholization in rats induced various histological changes in the frontal cortex, which were long-lasting and progressive during postnatal ontogeny.
7 citations
TL;DR: Comparative immunohistochemical studies of the dynamics of the expression of this pair of molecular markers provide an effective means of evaluating the development of cerebellar granule neurons during early postnatal ontogeny.
Abstract: Experiments were performed on the offspring of five mongrel white rats using comparative immunochemical assessments of doublecortin (DCX) and neuronal nuclear antigen (NeuN) expression in neurons in the cortex and nucleus interpositus of the cerebellum in animals during early postnatal ontogeny (days 2–15). DCX expression was seen in postmitotic neurons in the external granular layer and migrating neurons in the cerebellar cortex. DCX expression was greater in the neocerebellum than in the paleocerebellum in rat pups aged two and seven days. NeuN expression was seen in migrating granule neurons, reaching a maximum in more mature neurons in the internal granular layer. DCX expression was not seen in Purkinje cells or in neurons in the nucleus interpositus of the cerebellum. Neurons in the nucleus interpositus showed progressive increases in NeuN from day 2 to day 15 after birth. Thus, comparative immunohistochemical studies of the dynamics of the expression of this pair of molecular markers provide an effective means of evaluating the development of cerebellar granule neurons during early postnatal ontogeny.
7 citations
TL;DR: In this article, a review of the use of the Morris water maze to identify impairments to the cognitive functions of the brain as part of the evaluation of the toxic actions of nanoparticles is presented.
Abstract: We present here a review of the use of the Morris water maze to identify impairments to the cognitive functions of the brain as part of the evaluation of the toxic actions of nanoparticles. Model experiments showed that individual variability in animals’ behavior has significant influences on the results obtained in the water test. The need for preliminary selection of individuals as a measure to reduce such influences is grounded and the type of behavior displayed by the animal in the test to be used as the criterion for selection is discussed.
7 citations
TL;DR: Two methods of musical EEG biocontrol in which the subject’s dominant spectral EEG components were transformed into music-like signals with flute-like timbre were reported, accompanied by improvements in the subjects’ psychophysiological status.
Abstract: We report here studies of the effects of two methods of musical EEG biocontrol in which the subject’s dominant spectral EEG components (EEG oscillators) were transformed into music-like signals with flute-like timbre. In some cases, the pitches and intensities of these sound signals varied smoothly depending directly on the ongoing EEG amplitudes of the EEG oscillators. In other cases, variation in the pitch and intensity of flute sounds were supplemented by another musical characteristic – rhythm. Single exposures were found to produce modifications to the bioelectrical activity of the subject’s brain, which were accompanied by improvements in the subjects’ psychophysiological status. Effects were particularly marked when the musicality of exposures were increased by adding the property of rhythmicity.
TL;DR: The study results confirm the important role of HSP70 in the mechanisms of protection of the nigrostriatal system in proteasomal dysfunction typical of the preclinical stage of PD and provide scientific grounds for developing new techniques for the early treatment of PD based on Hsp70 preparations.
Abstract: Data obtained over the last ten years on the involvement of molecular chaperones of the heat shock protein 70 (HSP70) family in the pathogenesis of Parkinson’s disease (PD) do not provide an answer to the question of whether a decrease in the expression of stress-inducible Hsp70 in the brain is one of the causes of progression of neurodegeneration in PD. The present study used the HSP expression inhibitor quercetin in a model of proteasomal dysfunction in the nigrostriatal system in rats created by microinjection of the proteasome inhibitor lactacystin into the compact zone of the substantia nigra (SNc). This model reproduces subthreshold levels of nigrostriatal system degradation and neurochemical changes present in the preclinical stage of PD. We provide the first demonstration that preventive administration of quercetin prevents LC-induced Hsp70 expression in SNc neurons and leads to a 1.5-fold increase in the degeneration of dopaminergic neurons in the SNc and a 2.7-fold increase in the number of dopaminergic neuron axons in the striatum, with depletion of compensation processes and HSP70 reserves in SNc neurons. Signs of motor dysfunction typical of the clinical stage of PD were seen. The study results confirm the important role of Hsp70 in the mechanisms of protection of the nigrostriatal system in proteasomal dysfunction typical of the preclinical stage of PD. These data may provide scientific grounds for developing new techniques for the early treatment of PD based on Hsp70 preparations.
TL;DR: The presence of CMB is a marker for severe CI and a predictor for mixed pathology in CMB located cortically-subcortical and the corresponding neuropsychological profile.
Abstract: Objectives. To identify the significance of cerebral microbleeds (CMB) in the diagnosis of the main cerebrovascular and neurodegenerative diseases with cognitive impairments (CI). Materials and methods. MRI scans (1.5 T, T2* regime, gradient echo) were performed in 120 patients with Alzheimer’s disease (AD), Lewy body dementia (LBD), and vascular dementia to study CMB, their influence on the state of cognitive functions, and links with signs of vascular and neurodegenerative brain lesions. Neuropsychological studies were performed using the Montreal and Addenbrooke scales, including assessment of speech activity, the clock drawing test, and the pictures test. Results and discussion. CMB were detected in more than 1/3 patients with neurodegenerative and cerebrovascular pathologies; cortical CMB were mostly seen in neurodegenerative pathology and subcortical in cerebrovascular pathology, and these locations can be used for differential diagnosis. Single subcortical CMB were seen in 48% of patients with LBD, and these were accompanied by smaller numbers of lacunar infarcts and a lower severity of leukoaraiosis. In AD with additional signs of LBD and cerebrovascular disease, CMB was encountered more frequently (60%) and was a criterion for mixed pathology. Conclusions. Leukoaraiosis has great clinical significance in neurodegenerative and cerebrovascular diseases with CI, if accompanied by CMB. The presence of CMB is a marker for severe CI and a predictor for mixed pathology in CMB located cortically-subcortical and the corresponding neuropsychological profile.
TL;DR: These experiments showed that the pattern of intrinsic MMN differed significantly between words with different lexical frequencies, and the suggestion that there is superfast access to lexical information during speech perception is confirmed.
Abstract: We report here our studied on the influence of the lexical frequency of Russian words on the latency and amplitude of mismatch negativity (MMN) in auditory event-related potentials (ERP). ERP were recorded in a multideviant oddball paradigm by presenting different-frequency Russian words and pseudowords. These experiments showed that the pattern of intrinsic MMN differed significantly between words with different lexical frequencies (p = 0.001) – the higher the frequency, the greater the amplitude and the shorter the latent period of the intrinsic MMN of the words. It is suggested that the greater amplitude and shorter latency of MMN for high-frequency words as compared with the pattern of MMN for low-frequency words is due to activation of memory traces for these words, these being stored in the cerebral cortex as distributed neuron populations. The suggestion that there is superfast access to lexical information during speech perception is confirmed, with access being possible 100–200 msec after presentation of a word. The ratio of MMN amplitudes for different pseudowords was somewhat reminiscent of data on MMN for words (analogs of high-frequency words produced higher-amplitude responses, while analogs of low-frequency words produced weaker responses, with no significant difference between low- and intermediate-frequency analogs), though MMN amplitudes for pseudowords were significantly greater and latent periods were significantly longer. Increases in the amplitude and latency of MMN to pseudowords as compared with MMN to words is associated with later and uncertain recognition of rarely encountered low-frequency words and completely unfamiliar stimuli, which are later classified as signals of a different category.
TL;DR: In this article, EEG recordings were made as they performed a task with photographs of neutral faces of the characters in the film and photographs of the neutral face of fillers (characters not appearing in the movie) using event-related potentials (ERP).
Abstract: The ability to recognize faces is a key skill forming our social behavior. Much attention has been focused on studies of the perception of emotional faces and expressions, though the question of the effects of context on the face recognition process has received little study. Subjects in the studies reported here watched a video clip, after which EEG recordings were made as they performed a task with photographs of the neutral faces of the characters in the film and photographs of the neutral faces of fillers (characters not appearing in the film). Studies were performed using event-related potentials (ERP). Differences were found in the amplitude of the P200 component in responses to presentation of the faces of culprits and victims, which may be associated with the different subjective significance of these stimuli for the person watching the video clip. Correlations were also found between the subjects’ personality characteristics (anxiety, aggressivity, hostility) and increases in the amplitude of the P200 component in response to the faces of victims as compared with fillers. Further studies of the effects of emotional context on the perception of faces are required.
TL;DR: The most reliable indicators of behavior in the open field, reflecting a high probability of a significant increase in the corticosterone concentration after 3-h restraint, were a short latent period of first movement and a low level of motor activity.
Abstract: Studies were performed to assess the role of behavioral indicators in an open field test in predicting the blood corticosterone level in stress. The most reliable indicators of behavior in the open field, reflecting a high probability of a significant increase in the corticosterone concentration after 3-h restraint, were a short latent period of first movement and a low level of motor activity. The probability of high corticosterone in normal “unstressed” conditions is reflected by a low level of motor activity and, conversely, a long latent period for the excursion to the central squares of the field.
TL;DR: The ability of E. faecium L-3 to produce significant direct and indirect influences on the immune system in MS allows these bacteria to be regarded as a potential agent for immunocorrection in autoimmune, inflammatory, and neurodegenerative disease.
Abstract: The intestinal microbiota is currently regarded as a potential target for treatments in many pathologies underlying the genesis of inflammation, autoimmune reactions, and neurodegeneration. Multiple sclerosis (MS) is a disease whose pathogenesis combines all these processes. MS also involves impairment to the balance between the components of the intestinal microbiota, with development of dysbiosis. Various probiotics are widely used to correct dysbiotic conditions – bacteria with proven useful properties. We report here the use of a model of multiple sclerosis – experimental allergic encephalomyelitis (EAE) – to study the ability of the probiotic Enterococcus faecium strain L-3 to decrease disease severity in rats when used alone and in combination with glatiramer acetate (GA). Administration of E. faecium L-3 was found to decrease the severity of EAE in rats to essentially the same extent as GA. However, simultaneous use of probiotic enterococci with GA produced no protective action. It is suggested that these agents stimulate different components of the immune system, as their actions produce increases in different populations of immune cells circulating in the blood. The study results demonstrate the ability of E. faecium L-3 to produce significant direct and indirect (via correction of dysbacteriosis) influences on the immune system in MS, which allows these bacteria to be regarded as a potential agent for immunocorrection in autoimmune, inflammatory, and neurodegenerative disease.
TL;DR: The key role in forming the overall level of treatment compliance is played by the motivation mechanism based on subjective experience of suffering from the disorder, and extreme low levels of internal motivation based on an understanding of the nature of the disorder led to decreases in compliance associated with attitudes to treatment with medication.
Abstract: Objective. To identify interactions in the structure of treatment motivation and compliance in patients in a psychiatric clinic. Materials and methods. A questionnaire and compliance scales were used to assess treatment motivation in 104 patients in the Department of Integrative Pharmaco- and Psychotherapy. These included 67 patients with schizophrenia and schizoaffective spectrum disorders, 15 with affective disorders, 13 with personality disorders and neurotic disorders, and nine with organic lesions. Results and conclusions. The key role in forming the overall level of treatment compliance is played by the motivation mechanism based on subjective experience of suffering from the disorder. Occurrence of amotivation syndrome has disastrous effects on the formation of compliance. Passive agreement by the patient to accept treatment leads to a degradation in the treatment alliance, which is worsened by cognitive deficit in patients and reduced insight into the condition. Predominance of external motivation to receive treatment, determined by the pressure of the patient’s immediate environment, also had adverse impact on the compliance subsystem linked with the surroundings. Pressure from relatives was often not transformed into adequate social support. Extremely low levels of internal motivation based on an understanding of the nature of the disorder, led to decreases in compliance associated with attitudes to treatment with medication.
TL;DR: Systematic analysis of impairments to inhibitory processes in temporal epilepsy show that these result from the selective death of particular interneuron populations and from functional impairment to the operation of important interneurons.
Abstract: This review analyzes contemporary data on the possible roles of different classes of interneurons in the hippocampus and cortex in the pathogenesis of temporal epilepsy in humans – one of the commonest forms of epilepsy. Data obtained from humans (results of post mortem morphological investigation of patients’ brain tissues and electrophysiological experiments on brain slices collected at neurosurgical procedures) are considered, along with results from studies of in vivo and in vitro animal models of temporal epilepsy. Systematic analysis of impairments to inhibitory processes in temporal epilepsy show that these result from the selective death of particular interneuron populations and from functional impairments to the operation of important interneurons. Understanding of the concrete roles of different classes of interneurons in epilepsy is required for the development of new and effective treatment methods for this disease.
TL;DR: Emotional states in children with ASD were better recognized from the characteristics of vocalizations and speech than by facial expression, which has potential for developing methods of evaluating children’s status from the characteristic of their voices and for creating automatic speech recognition systems for training children with atypical development.
Abstract: The aim of the present work was to assess the ability of adults to recognize emotional state in typically developing (TD) children and children with diagnoses of autism spectrum disorders (ASD) in the history in terms of facial expressions, vocalizations, and speech signals. Participants in the study were children with ASD (ICD-10 F84.0) aged 5–16 years (n = 25) and TD children aged 4–7 years (n = 60). Stimulus material was selected on the basis of analysis of the children’s behavior and speech/vocalization in different emotional states. Features of the recognition by adults (n = 514) of emotional states in TD children and children with ASD were identified. Emotional states in children with ASD were better recognized from the characteristics of vocalizations and speech than by facial expression. This finding has potential for developing methods of evaluating children’s status from the characteristics of their voices and for creating automatic speech recognition systems for training children with atypical development.
TL;DR: In patients with initial assessments of at least 14 points on the NIH scale, Cytoflavin treatment for 20 days promoted more marked improvements in neurological, functional, and cognitive status than seen in patients given infusions for 10 days.
Abstract: Objective. To assess antioxidant therapy (ascorbic acid (AA), Cytoflavin) prescribed as part of the standard treatment scheme based on clinical and morphological data in cerebral infarct. Materials and methods. The study was performed from 2010 to 2014 in eight vascular centers in the Russian Federation. A total of 373 patients with acute ischemic stroke in the carotid basin were studied. Group 1 consisted of 132 patients who received 5% AA solution at a daily dose of 20 ml; group 2 consisted of 113 patients receiving the antioxidant Cytoflavin at a daily dose of 20 ml for 10 days; group 3 consisted of 108 patients receiving Cytoflavin for 20 days, the dose being decreased to 10 ml from day 11 to day 20. Patients’ status was evaluated using a set of clinical, laboratory, and instrumented methods. Results and conclusions. Analysis of CT scan results obtained on treatment days 1 and 21 showed that Cytoflavin led to significant regression of the volume of cerebral ischemia, by an average factor of 1.5–1.7. No significant morphological changes were seen in the AA-treated group; among Cytoflavin-treated patients there was a two-fold reduction in the proportion of patients in which the volume of cerebral ischemia increased during the period 1–21 days. In patients with initial assessments of at least 14 points on the NIH scale, Cytoflavin treatment for 20 days promoted more marked improvements in neurological, functional, and cognitive status than seen in patients given infusions for 10 days.
TL;DR: This review analyzes current progress in the modeling of depressive disorders in animals and provides for targeted studies of individual neurobiological mechanisms and patterns of development of depressive states in humans as well as studies of the mechanisms of action and predictions of the pharmacological profiles of potential drugs for the treatment of depression.
Abstract: This review analyzes current progress in the modeling of depressive disorders in animals. The criteria and classification systems for existing models are considered, as are approaches to assessing the validity of models. Despite the use of numerous approaches to modeling depressive states, based not only on impairments to the motivational mechanisms of the brain, but also on impairments to the emotional mechanisms, no satisfactory model creating a stable depressive state has yet been developed. Nonetheless, the diversity of existing models is undoubtedly positive, as it provides for targeted studies of individual neurobiological mechanisms and patterns of development of depressive states in humans, as well as studies of the mechanisms of action and predictions of the pharmacological profiles of potential drugs for the treatment of depression.
TL;DR: The role of impaired attention in forming the clinical picture of social impairment in autism is assessed, with the aim of determining whether deficient development of executive control may be an early indicator of hyperactivity symptoms.
Abstract: This article presents a review of current studies addressing the early signs of autism spectrum disorder (ASD). Autism spectrum disorder is a group of developmental impairments whose main signs are qualitative impairments to communication and social interactions. However, studies in recent years indicate that the earliest specific signs of the condition are impairments to the switching of attention and orientation to novel stimuli, with impairments to the processing of stimuli to which cells in the magnocellular visual pathway are sensitive, as well as deficient executive control. This article assesses the role of impaired attention in forming the clinical picture of social impairment in autism. Deficient development of executive control may be an early indicator of hyperactivity symptoms.
TL;DR: In this article, a review of the connections between the dynamics of action potential generation and the frequency coding abilities of neurons and neuronal networks is presented. But, despite the rapid development of neuron simulation in recent years, generally accepted models of nerve cells cannot provide a realistic description of the complete dynamics of activity potential generation in mammalian neurons or correct assessments of the ability of these cells to encode high-frequency signals.
Abstract: Recent studies have shown that the dynamics of action potential generation in neurons in vertebrates, in contrast to invertebrates, is significantly different from the slow exponential dynamics predicted by the Hodgkin–Huxley equations and is characterized by a sudden kink-like origin in the form of a steep linear increase. In this context, new and important aspects of studies of the links between the dynamics of action potential generation and the frequency coding abilities of neurons and neuronal networks have been found. This review addresses contemporary models describing the kink-type dynamics of action potential generation, including an alternative model of cooperative activation of potential-dependent sodium channels and the effects of the dynamics of action potential generation on the processing abilities of neural networks. The relevance of this direction comes from the fact that despite the rapid development of neuron simulation in recent years, generally accepted models of nerve cells cannot provide a realistic description of the complete dynamics of action potential generation in mammalian neurons or correct assessments of the ability of these cells to encode high-frequency signals. Contemporary experimental and theoretical analyses of action potential generation and neuronal encoding, as summarized in the present work, are highly significant for improving our understanding of nerve cell physiology and assisting the creation of more accurate and correct models of neurons.
TL;DR: Administration of release-active forms of antibody to S100 increased the latent period of disease onset, decreased in peak disease intensity, and compensated for weight loss in the animals, as compared with controls.
Abstract: Objective. To study the efficacy of release-active forms of antibody to S100 protein in an animal model of multiple sclerosis. Materials and methods. The study was performed on 60 female rats aged 12 weeks. Experimental allergic encephalomyelitis was induced by administration of spinal cord homogenate at the base of the tail. Female rats then received intragastric solution of release-active antibodies to S100 protein (Tenoten) at a dose of 2.5 ml/kg/day or distilled water for 30 days. Positive controls received i.m. injections of glatiramer acetate at a dose of 4 mg/kg/day (Copaxone). Results and discussion. Administration of release-active forms of antibody to S100 increased the latent period of disease onset, decreased in peak disease intensity, and compensated for weight loss in the animals, as compared with controls. The effect of the agents was comparable with that of the Copaxone group.
TL;DR: Regardless of the age at which the rat pups were subjected to treatments, repeated induction of inflammatory foci induced increased pain responses when animals reached adulthood, and in the forced swimming test, immobility was increased in rats subjected to any of the treatments.
Abstract: The long-term effects of peripheral inflammatory pain, transient maternal separation stress, and the combination of these factors on days 1 and 2 of life or on days 7 and 8 of life were studied in relation to measures of baseline pain (in the absence of an inflammatory process), prolonged responses to reinitiation of inflammation in the formalin test, levels of anxiety, extents of depressive behavior, and spatial learning ability when the animals reached adult age (90 days). In adult rats, study parameters showed changes depending on the type of early treatment and the age at which it was applied: inflammatory pain induced hypoalgesia in the hotplate test and degraded spatial learning ability in the Morris maze; maternal separation stress on days 1–2 but not days 7–8 increased pain responses in the formalin test. Regardless of the age at which the rat pups were subjected to treatments, repeated induction of inflammatory foci induced increased pain responses when animals reached adulthood. In the forced swimming test, immobility was increased in rats subjected to any of the treatments. The effects of combined pain and stress did not increase the influences of each applied alone. These new data contribute to the further development of our understanding of the longterm influences of harmful pain and stressors and their interactions in the neonatal period of development on the functional activity of the tonic nociception system and psychoemotional behavior.
TL;DR: It is suggested that the increase in the proportion of immunopositive neurons and the suppression of HIF-1α expression in brain hemocytes in anoxia play important roles in mediating compensatory and protective processes, increasing the adaptive potential of the mitten crab in conditions of hypoxic stress.
Abstract: Western immunoblotting and immunohistochemistry methods were used to study the expression of hypoxia-inducible factor 1α (HIF-1α) in the brain of the mitten crab Eriocheir japonica in normal conditions and anoxia lasting 2, 4, 6, and 12 h using a water deprivation model. The number of immunopositive neurons was small in intact crabs, and increased with increases in the duration of anoxia. There was a particularly marked increase in the proportion of neurons expressing HIF-1α in cells of group 6. In group 9/11, the highest values were seen at 2–6 h of anoxia. In group 17, significant changes in the proportion of immunopositive cells were noted only at 2 h of anoxia. After anoxia lasting 6 h, the proportion of neurons expressing HIF-1α decreased in all cell groups, though the reaction appeared in hemocytes. It is suggested that the increase in the proportion of immunopositive neurons and the suppression of HIF-1α expression in brain hemocytes in anoxia play important roles in mediating compensatory and protective processes, increasing the adaptive potential of the mitten crab in conditions of hypoxic stress.
TL;DR: The nucleus interpositus of the cerebellum showed an increase in the number and size of axosomatic synapses around neuron perikarya throughout the study period, and this was accompanied by a decrease in Syn immunoreactivity.
Abstract: The aim of the present work was to perform a qualitative and quantitative evaluation of synaptogenesis in the developing rat cerebellum (2–45 days after birth) by immunohistochemical detection of the marker synaptophysin (Syn). Syn expression was detected in postmitotic neurons in the external granular layer and migrating precursors of cerebellar granular neurons. The width of the synaptogenesis zone in the molecular layer increased throughout the study period, and this was accompanied by a decrease in Syn immunoreactivity. There was also a reduction in the number of Syn-immunopositive synapses around the perikarya of Purkinje cells from day 7 to day 15. The inner granular layer showed Syn-immunopositive dots, whose sizes increased from day 2 to day 45, which was associated with the formation of cerebellar glomeruli. The nucleus interpositus of the cerebellum showed an increase in the number and size of axosomatic synapses around neuron perikarya throughout the study period. Uneven groupings of Syn-positive axodendritic synapses appeared in the neuropil.
TL;DR: Measurements of grip strength, maximum voluntary contraction strength, and subjective assessments of fatigue before and after the motor tasks showed that experiments involving voluntary and involuntary attention to sound stimuli produced a smaller rate of development of muscle fatigue.
Abstract: The aim of the present work was to study the effects of cognitive loading requiring activation of the attention systems on the development of muscle fatigue. The dynamics of measures of arm muscle fatigue were evaluated in two sessions, separated by 5 min, consisting of 250 maximum-strength dynamometer compressions in response to acoustic target signals in three tasks with different levels of cognitive loading. The first experiment used only the target signals; in experiment two, the subjects had to discriminate the target signal from an equal number (250) of nontarget signals, which required voluntary attention. In experiment three, the proportions of target stimuli were 17 and 83%, respectively, i.e., the target stimulus was random (deviant), activating not only voluntary attention, but also involuntary attention. Measurements of grip strength, maximum voluntary contraction strength, and subjective assessments of fatigue before and after the motor tasks showed that experiments involving voluntary and involuntary attention to sound stimuli produced a smaller rate of development of muscle fatigue. Activation of involuntary attention, accompanied by the appearance of mismatch negativity on the EEG, enhanced the effect of voluntary attention.
TL;DR: Challenges of new multimodal therapeutic strategies for AD are discussed in relation to the current status of the amyloid hypothesis, and one component linking degenerative and vascular processes in AD is insulin resistance.
Abstract: The amyloid hypothesis of the development of Alzheimer’s disease (AD) continues to dominate, though the concept has changed significantly during its 25-year history. The accumulation of β-amyloid has been found to be linked not only with increase in its production (as found after elucidation of the genetic mechanisms of some familial cases of AD), but also with impairments to its clearance from brain tissues, which is mediated by the microcirculatory system. The most significant pathogenetic role in brain substance is played not by the senile plaques themselves, described by Alois Alzheimer almost 110 years ago and consisting of insoluble conjugates, but by soluble β-amyloid oligomers. The relationship between the vascular and degenerative processes in AD is supported by the common risk factors and by clinical, neuroimaging, pathomorphological, and experimental data. One component linking degenerative and vascular processes in AD is insulin resistance. Challenges of new multimodal therapeutic strategies for AD are discussed in relation to the current status of the amyloid hypothesis.