Nervous system

About: Nervous system is a research topic. Over the lifetime, 16729 publications have been published within this topic receiving 847181 citations.

Programmed cell death is a universal feature of embryonic and postnatal neuroproliferative regions throughout the central nervous system

Abstract: During central nervous system (CNS) development, programmed cell death (PCD) has been viewed traditionally as a fate reserved for differentiating neurons that are in the process of making synaptic connections. Recent studies in the embryonic cerebral cortex (Blaschke et al. [1996] Development 122:1165-1174), however, have shown that many neuroblasts in the proliferative ventricular zone undergo PCD as well and that this likely represents a novel form distinct from that found in regions of postmitotic neurons. To determine the commonality of this form of PCD throughout the CNS, the prevalence of dying cells identified by in situ end labeling plus (ISEL +; Blaschke et al. [1996]) was determined within populations of proliferating neuroblasts that were identified by rapid bromodeoxyuridine incorporation. Based on this approach, dying cells were observed to be a common feature of all proliferative neuroblast populations examined. In addition, when ISEL+ was combined with in situ hybridization for postmitotic neural gene-1 (png-1; Weiner and Chun [1997] J. Comp. Neurol. 381:130-142), which identifies newly postmitotic neurons, a positive correlation was found between the start of differentiation and the onset of PCD. These data indicate that PCD in neuroblast proliferative zones is a universal feature of nervous system development. Moreover, cell death represents a prominent cell fate that may be linked to mechanisms of differentiation.

Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment.

Abstract: The specific mechanisms by which nervous system injury becomes a chronic pain state remain undetermined. Historically, it has been believed that injuries proximal or distal to the dorsal root ganglion (DRG) produce distinct pathologies that manifest in different severity of symptoms. This study investigated the role of injury site relative to the DRG in (1) eliciting behavioral responses, (2) inducing spinal neuroimmune activation, and (3) responding to pharmacologic interventions. Rats received either an L5 spinal nerve transection distal to the DRG or an L5 nerve root injury proximal to the DRG. Comparative studies assessed behavioral nociceptive responses, spinal cytokine mRNA and protein expression, and glial activation after injury. In separate studies, intrathecal pharmacologic interventions by using selective cytokine antagonists (interleukin-1 [IL-1] receptor antagonist and soluble tumor necrosis factor [TNF] receptor) and a global immunosuppressant (leflunomide) were performed to determine their relative effectiveness in these injury paradigms. Behavioral responses assessed by mechanical allodynia and thermal hyperalgesia were almost identical in the two models of persistent pain, suggesting that behavioral testing may not be a sensitive measure of injury. Spinal IL-1beta, IL-6, IL-10, and TNF mRNA and IL-6 protein were significantly elevated in both injuries. The overall magnitude of expression and temporal patterns were similar in both models of injury. The degree of microglial and astrocytic activation in the L5 spinal cord was also similar for both injuries. In contrast, the pharmacologic treatments were more effective in alleviating mechanical allodynia for peripheral nerve injury than nerve root injury, suggesting that nerve root injury elicits a more robust, centrally mediated response than peripheral nerve injury. Overall, these data implicate alternate nociceptive mechanisms in these anatomically different injuries that are not distinguished by behavioral testing or the neuroimmune markers used in this study.

Collateral afferent excitation of reticular formation of brain stem.

Abstract: The demonstrable capacity of afferent stimulation to arouse a sleeping subject, and the obvious benefits of reducing sensory inflow in predisposing to sleep, are in seeming disharmony with recently discovered influences for wakefulness exerted by the central reticular core of the brain stem. Direct stimulation of this part of the neuraxis reproduces the electrical pattern of wakefulness in the cerebral cortex (14) while at the same time it facilitates lower motor activity (16), and so arouses the nervous system generally (9). The ascending course of this reticular activating system is distinct from that of afferent pathways in the brain stem (19) and selective destruction of its cephalic portion is followed by the EEG synchrony and behavioral somnolence, hitherto attributed to deafferentation of the cerebrum (7, 8). Such consequences do not follow selective interruption of ascending somatic and auditory paths in the midbrain and after this latter injury both somatic and auditory stimuli are still capable of awakening the sleeping animal and activating its EEG (7, 8). It seemed likely that the apparent conflict might be resolved if evidence were forthcoming that collaterals from afferent paths turned into the reticular activating system in the brain stem and exerted their admittedly important arousing and awakening influences, indirectly, by modifying its activity. The present study has explored this possibility by probing the brain stem for alterations in electrical activity evoked by somatic and auditory stimuli. The findings establish the existence of collaterals from these sensory systems to the brain stem reticular formation, the rich wealth of which has never previously been suspected, though indications for it have been afforded by earlier anatomical investigation (2, 11, 13) and by study of the atypical route of conduction of the ‘secondary response’ to sciatic stimulation (5). Though the results are presented here only with reference to the problem under discussion, it is felt that implications of these findings may be broad indeed, for they appear to enlarge outlooks in afferent conduction far beyond those which have been envisioned within the circumscribed limits imposed by classical sensory paths.

LEARNING MECHANISMS IN ADDICTION: Synaptic Plasticity in the Ventral Tegmental Area as a Result of Exposure to Drugs of Abuse

Abstract: One of the central questions in neurobiology is how experience modifies neural function, and how changes in the nervous system permit an animal to adapt its behavior to a changing environment. Learning and adaptation to a host of different environmental stimuli exemplify processes we know must alter the nervous system because the behavioral output changes after experience. Alterations in behavior after exposure to addictive drugs are a striking example of chemical alterations of nervous system function producing long-lasting changes in behavior. The alterations produced in the central nervous system (CNS) by addictive drugs are of interest because of their relationship to human substance abuse but also because these CNS alterations produce dramatic, easily observed alterations in behavior in response to discrete stimuli. Considerable study has been given to behavioral and biochemical correlates of addiction over the past 50 or more years; however, our understanding of the cellular physiological responses of affected CNS neurons is in its infancy. This review focuses on alterations in cellular and synaptic physiology in the ventral tegmental area (VTA) in response to addictive drugs.