Recent evidence suggests that neuronal plasticity plays an important role in the recovery from depression. Antidepressant drugs and electroconvulsive shock treatment increase the expression of several molecules, which are associated with neuronal plasticity, in particular the neurotrophin BDNF and its receptor TrkB. Furthermore, these treatments increase neurogenesis and synaptic numbers in several brain areas. Conversely, depression, at least in its severe form, is associated with reduced volumes of the hippocampus and prefrontal cortex and in at least some cases these neurodegenerative signs can be attenuated by successful treatment. Such observations suggest a central role for neuronal plasticity in depression and the antidepressant effect, and also implicate BDNF signaling as a mediator of this plasticity. The antidepressant fluoxetine can reactivate developmental-like neuronal plasticity in the adult visual cortex, which, under appropriate environmental guidance, leads to the rewiring of a developmentally dysfunctional neural network. These observations suggest that the simple form of the neurotrophic hypothesis of depression, namely, that deficient levels of neurotrophic support underlies mood disorders and increases in these neurotrophic factors to normal levels brings about mood recovery, may not sufficiently explain the complex process of recovery from depression. This review discusses recent data on the role of BDNF and its receptors in depression and the antidepressant response and suggests a model whereby the effects of antidepressant treatments could be explained by a reactivation of activity-dependent and BDNF-mediated cortical plasticity, which in turn leads to the adjustment of neuronal networks to better adapt to environmental challenges.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/dneu.20758

The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity.

Exercise is known to induce a cascade of molecular and cellular processes that support brain plasticity. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin that is also intimately connected with central and peripheral molecular processes of energy metabolism and homeostasis, and could play a crucial role in these induced mechanisms. This review provides an overview of the current knowledge on the effects of acute exercise and/or training on BDNF in healthy subjects and in persons with a chronic disease or disability. A systematic and critical literature search was conducted. Articles were considered for inclusion in the review if they were human studies, assessed peripheral (serum and/or plasma) BDNF and evaluated an acute exercise or training intervention. Nine RCTs, one randomized trial, five non-randomized controlled trials, five non-randomized non-controlled trials and four retrospective observational studies were analysed. Sixty-nine percent of the studies in healthy subjects and 86% of the studies in persons with a chronic disease or disability, showed a 'mostly transient' increase in serum or plasma BDNF concentration following an acute aerobic exercise. The two studies regarding a single acute strength exercise session could not show a significant influence on basal BDNF concentration. In studies regarding the effects of strength or aerobic training on BDNF, a difference should be made between effects on basal BDNF concentration and training-induced effects on the BDNF response following an acute exercise. Only three out of ten studies on aerobic or strength training (i.e. 30%) found a training-induced increase in basal BDNF concentration. Two out of six studies (i.e. 33%) reported a significantly higher BDNF response to acute exercise following an aerobic or strength training programme (i.e. compared with the BDNF response to an acute exercise at baseline). A few studies of low quality (i.e. retrospective observational studies) show that untrained or moderately trained healthy subjects have higher basal BDNF concentrations than highly trained subjects. Yet, strong evidence still has to come from good methodological studies. Available results suggest that acute aerobic, but not strength exercise increases basal peripheral BDNF concentrations, although the effect is transient. From a few studies we learn that circulating BDNF originates both from central and peripheral sources. We can only speculate which central regions and peripheral sources in particular circulating BDNF originates from, where it is transported to and to what purpose it is used and/or stored at its final destination. No study could show a long-lasting BDNF response to acute exercise or training (i.e. permanently increased basal peripheral BDNF concentration) in healthy subjects or persons with a chronic disease or disability. It seems that exercise and/or training temporarily elevate basal BDNF and possibly upregulate cellular processing of BDNF (i.e. synthesis, release, absorption and degradation). From that point of view, exercise and/or training would result in a higher BDNF synthesis following an acute exercise bout (i.e. compared with untrained subjects). Subsequently, more BDNF could be released into the blood circulation which may, in turn, be absorbed more efficiently by central and/or peripheral tissues where it could induce a cascade of neurotrophic and neuroprotective effects.

http://www.searlneuropsychology.com/uploads/5/1/2/1/5121658/kristel_et_al_2010_neuroplasticity_-_exercise-induced_response_of_peripheral_bdnf.pdf

Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects.

Nutrient transporters in cancer: Relevance to Warburg hypothesis and beyond

"Surgical Pathology of the Head and Neck, Third Edition " is a complete stand-alone reference dealing with head and neck pathology. Providing an interdisciplinary approach to the diagnosis, treatment, and management of head and neck diseases, and covering all aspects of general pathology - this is the reference of choice for head and neck pathologists, head and neck surgeons and pathologists promoting clear communication between pathologists and surgeons. With over 1200 photographs, micrographs, drawings, and tables - over 200 more illustrations than the second edition - head and neck pathologists, head and neck surgeons, otolaryngologists and pathologists will find this updated bestseller a valid reference for any practice. Unparalleled in scope and content than any other book available on the subject, "Surgical Pathology of the Head and Neck, Third Edition" is a must-have resource for oral, surgical, and general pathologists; otolaryngologists; oral, maxillofacial, plastic, reconstructive, general, head, neck, and orthopedic surgeons; and neurosurgeons, oncologists, hematologists, ophthalmologists, radiologists, endocrinologists, dermatologists, dentists, and residents and fellows in these disciplines.

Surgical Pathology of the Head and Neck

Glucose is the major energy source for mammalian cells as well as an important substrate for protein and lipid synthesis. Mammalian cells take up glucose from extracellular fluid into the cell through two families of structurallyrelated glucose transporters. The facilitative glucose transporter family (solute carriers SLC2A, protein symbol GLUT) mediates a bidirectional and energy-independent process of glucose transport in most tissues and cells, while the NaM(+)/glucose cotransporter family (solute carriers SLC5A, protein symbol SGLT) mediates an active, Na(+)-linked transport process against an electrochemical gradient. The GLUT family consists of thirteen members (GLUT1-12 and HMIT). Phylogenetically, the members of the GLUT family are split into three classes based on protein similarities. Up to now, at least six members of the SGLT family have been cloned (SGLT1-6). In this review, we report both the genomic structure and function of each transporter as well as intra-species comparative genomic analysis of some of these transporters. The affinity for glucose and transport kinetics of each transporter differs and ranges from 0.2 to 17mM. The ability of each protein to transport alternative substrates also differs and includes substrates such as fructose and galactose. In addition, the tissue distribution pattern varies between species. There are different regulation mechanisms of these transporters. Characterization of transcriptional control of some of the gene promoters has been investigated and alternative promoter usage to generate different protein isoforms has been demonstrated. We also introduce some pathophysiological roles of these transporters in human.

/pdf/functional-properties-and-genomics-of-glucose-transporters-5f9y86bqvy.pdf

Functional properties and genomics of glucose transporters.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.

https://www.mdpi.com/1422-0067/21/17/6000/pdf

Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity.

Human saliva chromogranin A (CgA) is clinically promising as a psychological stress marker. However, expression of CgA is poorly understood in humans, although salivary gland localization of CgA in other mammals, such as rodents and horses, has been demonstrated. In the present study, we investigated the expression and localization of CgA in the human submandibular gland (HSG) using various methods. CgA was consistently localized in serous and ductal cells in HSG, as detected by immunohistochemistry and in situhybridization. Reactivity was stronger in serous cells than in ductal cells. In addition, strong immunoreactivity for CgA was observed in the saliva matrix of ductal cavities. Western blotting gave one significant immunoreactive band of 68 kDa in the adrenal gland, HSG and saliva. Finally, CgA was detected in secretory granules of serous and ductal cells by immunoelectron microscopy. In conclusion, CgA in humans is produced by HSG and secreted into saliva.

Expression and Localization of Chromogranin A Gene and Protein in Human Submandibular Gland

Expression of Toll-like Receptor 2 and 4 in Dental Pulp

Mass spectrometry (MS)-based metabolomic methods enable simultaneous profiling of hundreds of salivary metabolites, and may be useful to diagnose a wide range of diseases using saliva. However, few studies have evaluated the effects of physiological or environmental factors on salivary metabolomic profiles. Therefore, we used capillary electrophoresis-MS to analyze saliva metabolite profiles in 155 subjects with reasonable oral hygiene, and examined the effects of physiological and environmental factors on the metabolite profiles. Overall, 257 metabolites were identified and quantified. The global profiles and individual metabolites were evaluated by principle component analysis and univariate tests, respectively. Collection method, collection time, sex, body mass index, and smoking affected the global metabolite profiles. However, age also might contribute to the bias in sex and collection time. The profiles were relatively unaffected by other parameters, such as alcohol consumption and smoking, tooth brushing, or the use of medications or nutritional supplements. Temporomandibular joint disorders had relatively greater effects on salivary metabolites than other dental abnormalities (e.g., stomatitis, tooth alignment, and dental caries). These findings provide further insight into the diversity and stability of salivary metabolomic profiles, as well as the generalizability of disease-specific biomarkers.

Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles

Schwannoma of the head and neck region is relatively uncommon. We report a case of schwannoma arising from the left mental nerve. A 21-year-old male presented at our hospital with a painless swelling of the left cheek. Because the lesion had rapidly increased in size, a malignant tumor was suspected. Magnetic resonance imaging (MRI), computed tomography, and ultrasonography were performed. MRI and ultrasonography revealed that the tumor was connected to the mental nerve. Both MRI and ultrasonography were found to be useful in making a preoperative diagnosis. It was possible to determine prior to surgery that this was a peripheral nerve sheath tumor. The lesion was completely resected. The pathological diagnosis was Antoni type A schwannoma. There has been no sign of recurrence 1 year after surgery.

Keiichi Tsukinoki

Papers

Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity.

Expression and Localization of Chromogranin A Gene and Protein in Human Submandibular Gland

Expression of Toll-like Receptor 2 and 4 in Dental Pulp

Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles

Schwannoma of the mental nerve: usefulness of preoperative imaging: a case report.