Central nervous system and computation

Computational systems are useful in neuroscience in many ways. For instance, they may be used to construct maps of brain structure and activation, or to describe brain processes mathematically. Furthermore, they inspired a powerful theory of brain function, in which the brain is viewed as a system characterized by intrinsic computational activities or as a "computational information processor. "Although many neuroscientists believe that neural systems really perform computations, some are more cautious about computationalism or reject it. Thus, does the brain really compute? Answering this question requires getting clear on a definition of computation that is able to draw a line between physical systems that compute and systems that do not, so that we can discern on which side of the line the brain (or parts of it) could fall. In order to shed some light on the role of computational processes in brain function, available neurobiological data will be summarized from the standpoint of a recently proposed taxonomy of notions of computation, with the aim of identifying which brain processes can be considered computational. The emerging picture shows the brain as a very peculiar system, in which genuine computational features act in concert with noncomputational dynamical processes, leading to continuous self-organization and remodeling under the action of external stimuli from the environment and from the rest of the organism.     

Central nervous system complications of endocarditis

Neurologic complications of infective endocarditis, risk factors for mortality and neurologic sequellae are briefly reviewed.     

Roles of the amyloid precursor protein family in the peripheral nervous system

Compelling evidence from in vivo model systems within the past decade shows that the APP family of proteins is important for synaptic development and function in the central and peripheral nervous systems. The synaptic role promises to be complex and multifaceted for several reasons. The three family members have overlapping and redundant functions in mammals. They have both adhesive and signaling properties and may, in principle, act as both ligands and receptors. Moreover, they bind a multitude of synapse-specific proteins, and we predict that additional interacting protein partners will be discovered. Transgenic mice with modified or abolished expression of APP and APLPs have synaptic defects that are readily apparent. Studies of the neuromuscular junction (NMJ) in these transgenic mice have revealed molecular and functional deficits in neurotransmitter release, in organization of the postsynaptic receptors, and in coordinated intercellular development. The results summarized here from invertebrate and vertebrate systems confirm that the NMJ with its accessibility, large size, and homogeneity provides a model synapse for identifying and analyzing molecular pathways of APP actions.     

Central nervous system regulation of adipocyte metabolism

The white adipose tissue was initially largely known only as an energy storage tissue. It is now well recognized that white adipose tissue is a major endocrine and secretory organ, which releases a wide range of protein signals and factors termed adipokines. The regulation of adipocyte metabolism is an important factor for the understanding of obesity, and some mechanisms are still unknown. Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the central nervous system. There is substantial evidence demonstrating that the central nervous system also directly regulates adipocyte metabolism. In this review, we discuss the central actions of some peptides with an important role in energy balance regulation on adipocyte metabolism and the physiological relevance of these actions.     

Central nervous system and mechanisms of hypertension

There are several mechanisms by which the central nervous system participates in the neural and humoral alterations associated with various forms of experimental hypertension. Structures in forebrain with multiple integrative roles in neuroendocrine control of the circulation are involved. Tissue surrounding the anteroventral region of the third cerebral ventricle (AV3V region) is involved physiologically in thirst, sodium homeostasis, osmoreception, secretion of vasopressin and natriuretic factor and sympathetic discharge to blood vessels. Destruction of this tissue prevents or reverses many forms of hypertension. In genetically based spontaneous hypertension, limbic structures such as the central nucleus of the amygdala rather than the AV3V region are the necessary neuroanatomic substrate. Recent evidence suggests that a circumventricular organ in brain stem, the area postrema, is also involved in the mediation of several forms of experimental hypertension. In renin- and nonrenin-dependent forms of renal hypertension, two major factors activate central mechanisms. First, direct central actions of angiotensin, acting through receptors in the subfornical organ and organum vasculosum of the lamina terminalis, increase sympathetic discharge and secretion of vasopressin through mechanisms integrated at the level of the AV3V region. Second, sensory systems originating in the kidney can activate increased sympathetic discharge through complex projection pathways involving forebrain systems. Mineralocorticoid hypertension appears to involve enhanced secretion of vasopressin and central vasopressinergic mechanisms also dependent on the AV3V region. Reciprocal connections between key central areas involved in control of arterial pressure provide the neuroanatomical basis for central nervous system participation in hypertension.     

Central nervous system mechanisms for pain modulation

Although a great deal has been learned about the neural basis for stimulation-produced analgesia, it is evident that the 'analgesia systems' are much more complex than was initially thought. Part of the complexity derives from the fact that a number of different pathways, using several different neurotransmitters, can affect nociceptive transmission. Further complexity stems from evidence that nociceptive transmission can be modulated both at a spinal cord level and at higher levels of the nociceptive projection system, such as the thalamus. Hopefully, a greater understanding of the 'analgesia systems' will lead to explanations for a number of puzzling aspects of pain and perhaps to improved therapy.     

Central nervous system injury-induced immune deficiency syndrome

Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency - CNS injury-induced immunodepression (CIDS) - and infection. CIDS might serve as a model for the study of the mechanisms and mediators of brain control over immunity. More importantly, understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.     

Central nervous system mechanisms of arterial pressure regulation

This paper provides a review of recent developments in the field of neural and humoral control of the cardiovascular system mediated through the central nervous system. The areas covered include central mechanism of baroreceptor reflex control, sites of origin of tonic vasomotor activity, interactions between forebrain and brain stem, central actions of humoral factors, the role of visceral and somatic afferents, and the potential for central selectivity of vasomotor control.     

LIM同源框基因家族与神经系统

同源框基因是指一类含有同源序列的基因,它编码的蛋白质作为转录调节因子调节细胞的发育和分化,控制基因的表达形式。ＬＩＭ同源框基因不仅含有同源框基因也含有编码ＬＩＭ结构域的保守序列。     

Src family kinases in the nervous system

Src family kinases (SFKs) are key factors in the process of coupling signals from the cell surface to intracellular machinery and critically involved in the regulation of many neural functions mediated through growth factors, G-protein-coupled receptors or ligand-gated ion channels. The three minireviews here focus on recent findings dealing with the regulation of N-methyl-d-aspartate (NMDA) receptors by SFKs.     

Central nervous system function in systemic lupus erythematosus

Autoantibodies to three eukaryotic 60S ribosomal phosphoproteins P0, P1 and P2 have been found in the sera of 10–20% of patients with systemic lupus erythematosus (SLE). These antibodies inhibit protein synthesis in vitro and when microinjected into cultured human fibroblasts. The three proteins share a common epitope contained within the carboxyl terminal 22 amino acids of each protein. Because a significant number of SLE patients have central nervous system disturbances with major behavioral disorders, the antiribosomal protein autoantibodies were measured in this subset of SLE individuals to determine whether or not there was an association. These antibodies are present in 90% of SLE patients who were diagnosed as having psychosis, secondary to the disease.Special issue dedicated to Dr. Sidney underfriend     

JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions

The serine-threonine kinase PAK1 is activated by small GTPase-dependent and -independent mechanisms and promotes cell survival. However, the role of tyrosyl phosphorylation in the regulation of PAK1 function is poorly understood. In this study, we have shown that the prolactin-activated tyrosine kinase JAK2 phosphorylates PAK1 in vivo. Wild type, but not kinase-dead, JAK2 directly phosphorylates PAK1 in cells and in an in vitro kinase assay. PAK1 tyrosines 153, 201, and 285 were identified as sites of JAK2 tyrosyl phosphorylation by mass spectrometry and two-dimensional peptide mapping. Mutation of PAK1 tyrosines 153, 201, and 285 to phenylalanines individually or in combination implicated these PAK1 tyrosines in the regulation of PAK1 kinase activity. Tyrosyl phosphorylation by JAK2 significantly increases PAK1 kinase activity, whereas similar phosphorylation of the PAK1 Y153F,Y201F,Y285F mutant has no effect on PAK1 activity. Tyrosyl phosphorylation of wild type PAK1 decreases apoptosis induced by serum deprivation and staurosporine treatment and increases cell motility. In contrast, these parameters are unaltered in the PAK1 Y153F,Y201F,Y285F mutant. Our findings indicate that JAK2 phosphorylates PAK1 at these specific tyrosines and that this phosphorylation plays an important role in cell survival and motility.     

Extracellular matrix: functions in the nervous system

An astonishing number of extracellular matrix glycoproteins are expressed in dynamic patterns in the developing and adult nervous system. Neural stem cells, neurons, and glia express receptors that mediate interactions with specific extracellular matrix molecules. Functional studies in vitro and genetic studies in mice have provided evidence that the extracellular matrix affects virtually all aspects of nervous system development and function. Here we will summarize recent findings that have shed light on the specific functions of defined extracellular matrix molecules on such diverse processes as neural stem cell differentiation, neuronal migration, the formation of axonal tracts, and the maturation and function of synapses in the peripheral and central nervous system.     

Fibrin mechanisms and functions in nervous system pathology

In brain physiology, cerebrovascular interactions regulate both, vascular functions, such as blood vessel branching and endothelial cell homeostasis, as well as neuronal functions, such as local synaptic activity and adult neurogenesis. In brain pathology, including stroke, HIV encephalitis, Alzheimer Disease, multiple sclerosis, bacterial meningitis, and glioblastomas, rupture of the vasculature allows the entry of blood proteins into the brain with subsequent edema formation and neuronal damage. Fibrin is a blood-derived protein that is not produced by cells of the nervous system, but accumulates only after disease associated with vasculature rupture. This review presents evidence from human disease and animal models that highlight the role of fibrin in nervous system pathology. Our review presents novel experimental data that extend the role of fibrin, from that of a blood-clotting protein in cerebrovascular pathologies, to a component of the perivascular extracellular matrix that regulates inflammatory and regenerative cellular responses in neurodegenerative diseases.