Wiley
0022-3034
1097-4695
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Các bài báo tiêu biểu
Excitotoxic cell death Abstract Excitotoxicity refers to the ability of glutamate or related excitatory amino acids to mediate the death of central neurons under certain conditions, for example, after intense exposure. Such excitotoxic neuronal death may contribute to the pathogenesis of brain or spinal cord injury associated with several human disease states. Excitotoxicity has substantial cellular specificity and, in most cases, is mediated by glutamate receptors. On average, NMDA receptors activation may be able to trigger lethal injury more rapidly than AMPA or kainate receptor activation, perhaps reflecting a greater ability to induce calcium influx and subsequent cellular calcium overload. It is possible that excitotoxic death may share some mechanisms with other forms of neuronal death. © 1992 John Wiley & Sons, Inc.
Tập 23 Số 9 - Trang 1261-1276 - 1992
The Trk family of neurotrophin receptors Abstract Accumulating evidence indicates that the Trk family of tyrosine protein kinase receptors, Trk (also known as TrkA), TrkB, and TrkC, are responsible for mediating the trophic effects of the NGF family of neurotrophins. Nerve growth factor (NGF) specifically recognizes Trk, a receptor indentified in all major NGF targets, including sympathetic, trigeminal, and dorsal root ganglia as well as in cholinergic neurons of the basal forebrain and the striatum. Brain‐derived neurotropic factor (BDNF) and neurotrophin‐4 (NT‐4) specifically activate the TrkB tyrosine kinase receptor. trk B transcripts encoding this receptor are found throughout multiple structure of the central and peripheral nervous system. Neurotrophin‐3 (NT‐3) primarily activates the TrkC tyrosine protein kinases, four related isoforns encoded by alternative splicing of trk C, a gene also wildely expressed throughtout the mammalian nervous system. Unlike the other neurotrophins, NT‐3 appears to be somewhat promiscuous since it can activate Trk and TrkB kinase receptors, at least in certain cell systems. The trk B and trkC genes also encode noncatalytic neurotrophin receptor isoforms of an as yet, unknown function. Recently, strains of mice lacking each of these tyrosine kinase receptors have been generated. Preliminary characterization of these mutant mice has provided significant information regarding the role of these receptors in the ontogeny of the mammlian nervous system. For instance, mice deficient for Trk receptors lack most sympathetic neurons and do not display nociceptive and temperature sensations, two defects likely to result from severe neuronal cell loss in their trigeminal and dorsal root ganglia. Mice lacking TrkB tyrosine kinase receptors die postnatally due to their inability to intake food. Neuron cell loss in their trigeminal, nodose and pretrosal sensory ganglia as well as in the facial motor nucleus are likely to contribute to this phenotype. Finally, TrkC‐deficient mice display strikingly abnormal movements consistent with loss of proprioception, a defect likely to be a consequence of the complete loss of Ia muscle afferents observed in this mutant mice. 1994 John Wiley & Sons, Inc.
Tập 25 Số 11 - Trang 1386-1403 - 1994
Conditional modification of behavior in<i>Drosophila</i>by targeted expression of a temperature‐sensitive<i>shibire</i>allele in defined neurons Abstract Behavior is a manifestation of temporally and spatially defined neuronal activities. To understand how behavior is controlled by the nervous system, it is important to identify the neuronal substrates responsible for these activities, and to elucidate how they are integrated into a functional circuit. I introduce a novel and general method to conditionally perturb anatomically defined neurons in intactDrosophila . In this method, a temperature‐sensitive allele ofshibire (shi ts1 GAL4 /UAS system. Because theshi gene product is essential for synaptic vesicle recycling, andshi ts1 shi ts1 shi ts1 shi ts1 GAL4 /UAS system can be used to expressshi ts1
Tập 47 Số 2 - Trang 81-92 - 2001
Chronic stress alters dendritic morphology in rat medial prefrontal cortex Abstract Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. Medial prefrontal cortex is a target for glucocorticoids involved in the stress response. We have previously demonstrated that 3 weeks of daily corticosterone injections result in dendritic reorganization in pyramidal neurons in layer II–III of medial prefrontal cortex. To determine if similar morphological changes occur in response to chronic stress, we assessed the effects of daily restraint stress on dendritic morphology in medial prefrontal cortex. Male rats were exposed to either 3 h of restraint stress daily for 3 weeks or left unhandled except for weighing during this period. On the last day of restraint, animals were overdosed and brains were stained using a Golgi‐Cox procedure. Pyramidal neurons in lamina II–III of medial prefrontal cortex were drawn in three dimensions, and the morphology of apical and basilar arbors was quantified. Sholl analyses demonstrated a significant alteration of apical dendrites in stressed animals: overall, the number and length of apical dendritic branches was reduced by 18 and 32%, respectively. The reduction in apical dendritic arbor was restricted to distal and higher‐order branches, and may reflect atrophy of terminal branches: terminal branch number and length were reduced by 19 and 35%. On the other hand, basilar dendrites were not affected. This pattern of dendritic reorganization is similar to that seen after daily corticosterone injections. This reorganization likely reflects functional changes in prefrontal cortex and may contribute to stress‐induced changes in cognition. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 236–248, 2004
Tập 60 Số 2 - Trang 236-248 - 2004
Multiple forms of acetylcholinesterase and their distribution in endplate and non‐endplate regions of rat diaphragm muscle Abstract The properties of the cholinesterase activity in homogenates of whole rat diaphragm and of innervated (+EP) and non‐innervated (−EP) regions of the muscle have been investigated. Under standard assay conditions, over 90% of the cholinesterase activity of whole muscle homogenates was due to specific acetylcholinesterases. The specific activity of acetylcholinesterase was higher in +EP regions of muscle than in −EP regions. About 40% of the total activity was calculated to be specifically associated with the endplates. When a high speed supernatant fraction of muscles homogenized in 1 M NaCl, 0.5% Triton X‐100 was subjected to velocity sedimentation in a sucrose gradient, and three species of acetylcholinesterase activity with sedimentation constants of 4 S, 10 S and 16 S were observed. All three forms were stable under the conditions of sedimentation and had buoyant densities of approximately 1.28. All three hydrolyzed β‐methylacetylcholine at approximately 30% the rate that acetylcholine was hydrolyzed. The 10 S and 16 S forms were inhibited by concentrations of acetylcholine over 1.25 mM, but no substrate inhibition was observed with the 4 S enzyme. Velocity sedimentation of extracts from +EP and −EP regions of muscle demonstrated that the 4 S and 10 S forms of the enzyme were distributed throughout the muscle while the 16 S form was found only in +EP regions. Extracts of the phrenic nerve contained only 4 S and 10 S forms. Thus, the 16 S form of acetylcholinesterase is specifically associated with endplate regions of muscle and may correspond to the endplate enzyme. Seven days after denervation of the diaphragm, both endplate‐specific cholinesterase activity and the cholinesterase activity in −EP regions of muscle were decreased. Although the activity of all three forms of acetylcholinesterase were decreased in denervated muscle, the largest proportional decrease occurred in the activity of the 16 S form.
Tập 4 Số 4 - Trang 343-361 - 1973
Cellular and synaptic mechanisms of nicotine addiction Abstract The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid with nicotinic acetylcholine receptors (nAChRs). This interaction leads to activation of reward centers in the CNS, including the mesoaccumbens DA system, which ultimately leads to behavioral reinforcement and addiction. Recent findings from a number of laboratories have provided new insights into the biologic processes that contribute to nicotine self‐administration. Examination of the nAChR subtypes expressed within the reward centers has identified potential roles for these receptors in normal physiology, as well as the effects of nicotine exposure. The high nicotine sensitivity of some nAChR subtypes leads to rapid activation followed in many cases by rapid desensitization. Assessing the relative importance of these molecular phenomena in the behavioral effects of nicotine presents an exciting challenge for future research efforts. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 606–617, 2002
Tập 53 Số 4 - Trang 606-617 - 2002
Cholinergic interneuron characteristics and nicotinic properties in the striatum Abstract The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 590–605, 2002
Tập 53 Số 4 - Trang 590-605 - 2002
Fos: An immediate‐early transcription factor in neurons Abstract In the past several years a great deal of evidence has accumulated linking neuronal activation events to the regulation of gene expression. We have pursued an analysis of c‐fos regulation in the nervous system to elucidate the molecular mechanisms involved in stimulus‐transcription coupling. The c‐fos gene can be viewed as an archetype of the set of cellular immediate‐early genes encoding transcription factors. These genes are believed to function in coupling short‐term signals elicited by extracellular to long‐term changes in cellular phenotype by orchestrating alterations in target gene expression. Several animal seizure models have been used to demonstrate the activation of gene expression in specific populations of neurons. Using a transgenic mouse approach, based on a foslacZ fusion gene, we now demonstrate an association between c‐fos expression and cell death in the nervous system. A delayed and protracted induction was observed following surgical lesion and in response to neurotoxin exposure. This system allows us to determine, for the first time, the DNA regulatory sequences that are responsible for the induction of gene expression in neurons in vivo . Furthermore, foslacZ transgenic mice provide a unique resource for identifying cell populations that respond to specific stimuli or that are susceptible to particular toxins. © 1995 John Wiley & Sons, Inc.
Tập 26 Số 3 - Trang 403-412 - 1995
Long‐term culture of mouse cortical neurons as a model for neuronal development, aging, and death Abstract A long‐term cell culture system was used to study maturation, aging, and death of cortical neurons. Mouse cortical neurons were maintained in culture in serum‐free medium (Neurobasal supplemented with B27) for 60 days in vitro (DIV). The levels of several proteins were evaluated by immunoblotting to demonstrate that these neurons matured by developing dendrites and synapses and remained continuously healthy for 60 DIV. During their maturation, cortical neurons showed increased or stable protein expression of glycolytic enzyme, synaptophysin, synapsin IIa, α and β synucleins, and glutamate receptors. Synaptogenesis was prominent during the first 15 days and then synaptic markers remained stable through DIV60. Very early during dendritic development at DIV3, β‐synuclein (but not α‐synuclein) was localized at the base of dendritic growth cones identified by MAP2 and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole (AMPA) receptor GluR1. In mature neurons, α and β synucleins colocalized in presynaptic axon terminals. Expression of N ‐methyl‐D ‐aspartate (NMDA) and AMPA receptors preceded the formation of synapses. Glutamate receptors continued to be expressed strongly through DIV60. Cortical neurons aging in vitro displayed a complex profile of protein damage as identified by protein nitration. During cortical neuron aging, some proteins showed increased nitration, while other proteins showed decreased nitration. After exposure to DNA damaging agent, young (DIV5) and old (DIV60) cortical neurons activated apoptosis mechanisms, including caspase‐3 cleavage and poly(ADP)‐ribose polymerase inactivation. We show that cultured mouse cortical neurons can be maintained for long term. Cortical neurons display compartmental changes in the localization of synucleins during maturation in vitro . These neurons sustain protein nitration during aging and exhibit age‐related variations in the biochemistry of neuronal apoptosis. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 9–23, 2002
Tập 51 Số 1 - Trang 9-23 - 2002
Effects of environmental enrichment and impoverishment on rat cerebral cortex Abstract The first part of this paper deals with rat brain anatomy as affected by variations of starting age and of duration of exposure to enriched (complex) or impoverished (restricted) environmental conditions. Cerebral cortical depth measurements and weights of brain samples are compared. The second part of this report is concerned with an attempt to establish the extent to which the enriched condition or the improverished condition is responsible for the histological brain changes; this is done by comparison with brains from animals in the standard colony environment. The results indicate that both larger and more extensive cortical depth effects are found in rats exposed for 30 days rather than 80 days to their respective environments. The effects of enrichment are more prominent in the dorsal cortical segments, whereas the effects of impoverishment are more evident in the lateral cortical segments. More precise localization of cortical changes is obtained by measuring the depths at many segments than by taking the weights of relatively large blocks of tissue.
Tập 3 Số 1 - Trang 47-64 - 1972