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At least 1,783 records · Page 99Linked to original sources
PubMed1996

Matrix metalloproteinases in the neocortex and spinal cord of amyotrophic lateral sclerosis patients.

Matrix metalloproteinases (MMPs) were analyzed by immunohistochemistry and zymography in amyotrophic lateral sclerosis (ALS) and control brain and spinal cord specimens. Three major bands of enzyme activity (70, 100, and 130 kDa) were consistently observed and were subsequently identified as MMP-2 (70 kDa; also known as EC 3.4.24.24 or gelatinase A) and MMP-9 (100 and 130 kDa; also known as EC 3.4.24.35 or gelatinase B). Immunohistochemical studies established the presence of MMP-2 in astrocytes and MMP-9 in pyramidal neurons in the motor cortex and motor neurons in the spinal cord of ALS patients. Although a significant decrease in MMP-2 activity was noticed in the ALS motor cortex, statistically significant increases in MMP-9 (100-kDa) activity were observed in ALS frontal and occipital cortices (BA10 and 17) and all three spinal cord regions when compared with control specimens. The highest MMP-9 (100-kDa) activities in ALS were found in the motor cortex and thoracic and lumbar cord specimens. The abnormally high amount of MMP-9 and its possible release at the synapse may destroy the structural integrity of the surrounding matrix, thereby contributing to the pathogenesis of ALS.

Aged↗
PubMed2001

Evidence that increases of mitochondrial immunoreactive IL-1beta by HIV-1 gp120 implicate in situ cleavage of pro-IL-1beta in the neocortex of rat.

Immunoelectron microscopy analysis of brain tissue sections and rat-specific sandwich ELISA allowed the localization of interleukin-1beta (IL-1beta) immunoreactivity in the mitochondria and cytosol of neocortical tissue preparations from the brain of naive, untreated, rats and rats receiving a single daily injection into one lateral cerebral ventricle (i.c.v.) of bovine serum albumin (BSA; 100 ng/day) for seven consecutive days. Interestingly, seven days i.c.v. treatment with the HIV-1 coat protein gp120 (100 ng/day) enhances IL-1beta immunoreactivity in the cellular fractions studied. Elevation of mitochondrial immunoreactive IL-1beta levels seems to originate from the conversion operated by the interleukin converting enzyme (ICE) of mitochondrial pro-IL-1beta; in fact, IL-1beta increases reported in the ELISA experiments were paralleled by a decrease of the mitochondrial pro-IL-1beta 31-kDa band in conjunction with enhanced expression of the p20 component of activated ICE. In conclusion, the present results demonstrate that gp120-enhanced neocortical expression of IL-1beta originates, at least in part, from in situ cleavage of mitochondrial pro-IL-1beta and suggest that this, together with the central role of the mitochondrion in the expression of programmed cell death, may be important for apoptosis induced by the viral coat protein in the brain of rats.

Animals↗
PubMed1991

Constitutive expression of zif268 in neocortex is regulated by synaptic activity.

Transcription factors are rapidly and transiently induced in brain by excitatory stimuli and may be important in coordinating changes in gene expression underlying neuronal plasticity. In contrast to their transient induction after stimulation, certain transcription factors display stable, relatively high basal levels of expression in brain. Here we demonstrate that this "constitutive" expression of the transcription factor zif268 in cortex is driven by natural synaptic activity. Blockade of afferent visual activity with intraocular injections of tetrodotoxin results in rapid, dramatic reductions of Zif268 mRNA and immunoreactivity in visual cortex. Moreover, dark-adaptation for several days lowers zif268 expression in visual cortex, and expression rapidly returns to control levels upon subsequent light exposure. Several other transcription factors, which are induced in cortical neurons by excitatory stimuli, appear less responsive to changes in natural sensory input. These studies suggest that transcription factors play a role not only in responses to artificial stimuli but also in the normal maintenance of cortical physiology. Anatomic markers for zif268 may be useful in mapping normal cortical activity in brain.

Animals↗
PubMed1991

Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenzepine high-affinity muscarinic sites (M1) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca mulatta). Carbachol competition experiments detected only a single, low-affinity class of sites in old monkeys, while two classes of sites (low and high affinity) were observed in young adults. The change in affinity in the aged monkeys is not accompanied by a decrease in the density of these sites and, further, the age-related decline in the affinity of the M1 site is reversible. In the presence of Mg2+, the M1 muscarinic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for age-dependent functional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategic target for research aimed at treatment of memory disorders in aged humans.

Aging↗
PubMed1994

Mode of cell proliferation in the developing mouse neocortex.

There are two proliferative populations in the developing cerebral wall: the pseudostratified ventricular epithelium (PVE) and the secondary proliferative population (SPP). The present experiments provide on embryonic day 14 (E14) in the mouse direct measures of the values for the proportions of daughter cells that continue to proliferate (proliferative, P fraction, or P) and for those that leave the cell cycle (quiescent, Q fraction, or Q; Q = 1 - P) for both of these populations. The range of values of P for the PVE, 0.62-0.66, would provide for the relatively low rate of neuronal output and for an expansion of the proliferative population appropriate for E14. The even higher values of P for the SPP, 0.73-1.0, would expand this population rapidly in preparation for the high glial cell output to occur later in cerebral histogenesis.

Animals↗
PubMed1996

Short-term synaptic enhancement and long-term potentiation in neocortex.

Repetitive stimuli reliably induce long-term potentiation (LTP) of synapses in the upper layers of the granular somatosensory cortex but not the agranular motor cortex of rats. Herein we examine, in these same cortical areas, short-term changes in synaptic strength that occur during the LTP induction period. theta-Burst stimulation produced a strong short-term enhancement of synapses in the granular area but only weak enhancement in the agranular area. The magnitude of enhancement during stimulation was strongly correlated with the magnitude of LTP subsequently expressed. Short-term enhancement was abolished by an antagonist of N-methyl-D-aspartate (NMDA) receptors but remained in the presence of a non-NMDA receptor antagonist. Inhibitory postsynaptic potentials of the granular and agranular areas displayed similar frequency sensitivity, but the frequency sensitivity of NMDA receptor-dependent excitatory postsynaptic potentials differed significantly between areas. We propose that pathway-specific differences in short-term enhancement are due to variations in the frequency dependence of NMDA currents; different capacities for short-term enhancement may explain why repetitive stimulation more readily induces LTP in the somatosensory cortex than in the motor cortex.

2-Amino-5-phosphonovalerate↗
PubMed1997

Age-dependent decrease of synaptic plasticity in the neocortex of alphaCaMKII mutant mice.

Synaptic long-term potentiation (LTP) and long-term depression (LTD) were studied in the visual cortex of mutant mice lacking alpha-calcium/calmodulin-dependent protein kinase II (alphaCaMKII). In adult mutants, little LTD or LTP could be elicited using standard conditioning protocols. However, substantial LTD and LTP were induced in 4- to 5-week-old mutants. Thus, the reduction in cortical plasticity in alphaCaMKII (-/-) mice is conditional, with the relevant condition being postnatal age.

Aging↗
PubMed1997

Distinct forms of short-term plasticity at excitatory synapses of hippocampus and neocortex.

The expression of short- and long-term synaptic plasticity varies strongly across pathways in the central nervous system. Differences in the properties of transmitter release may underlie some of this variability. Here we compared the short-term plasticity displayed by a neocortical and a hippocampal pathway in vitro, and observed dramatic differences. Conditions known to increase transmitter release probability were more effective in hippocampus, while conditions known to decrease release probability were similarly effective in both pathways. The effects of the irreversible open-channel blocker of N-methyl-D-aspartate receptors, MK-801, implied that synapses in the neocortical pathway have a relatively high probability of transmitter release as compared with synapses in the hippocampal pathway. Differences in release probability may explain the pathway-specific variance in short- and long-term synaptic plasticity.

Animals↗
PubMed2000

Abeta 1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation.

Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta peptide (Abeta), play a critical role in the pathogenesis of Alzheimer's dementia. We report that transgenic mice overexpressing APP and Abeta have a profound attenuation in the increase in neocortical blood flow elicited by somatosensory activation. The impairment is highly correlated with brain Abeta concentration and is reproduced in normal mice by topical neocortical application of exogenous Abeta1-40 but not Abeta1-42. Overexpression of M146L mutant presenilin-1 in APP mice enhances the production of Abeta1-42 severalfold, but it does not produce a commensurate attenuation of the hyperemic response. APP and Abeta overexpression do not diminish the intensity of neural activation, as reflected by the increase in somatosensory cortex glucose usage. Thus, Abeta-induced alterations in functional hyperemia produce a potentially deleterious mismatch between substrate delivery and energy demands imposed by neural activity.

Amyloid beta-Peptides↗
PubMed1976

Neocortex development during severe malnutrition in the rat.

Histological methods (Golgi-Cox and Nissl) were used to study the maturation of the large pyramidal cells of layer V of the occipital cortex in malnourished rats (according to the method of Araya et al.). The main alterations were observed in pyramidal cells of cortical alyer V; These showed a decrease of the number and span of dendritic basilar processes. An increase in cell density was also observed in this layer. We assume that malnutrition during this period of development provokes a derangement which disturbs the process of neuron differentiation, with effects that probably are permanent.

Animals↗
PubMed1991

Role of the right temporal neocortex in retention of pitch in auditory short-term memory.

In order to investigate the neural mechanisms underlying short-term memory for auditory information, 71 patients who had undergone focal excision from the left or right temporal or right frontal or fronto-temporal area for the relief of intractable epilepsy were tested, together with 18 normal control subjects, on a task requiring short-term retention of tonal pitch. In the control condition, a target tone was presented, followed 1650 ms later by a comparison tone, and subjects determined whether the two had the same pitch or not. In the interference condition a series of interpolated tones was presented between target and comparison tone. Results indicated that there was no significant impairment in any patient group on the control task. In the interference task there was a significant deficit in retention of tonal information in the patients with right temporal-lobe damage, as well as in those with lesions in the right frontal lobe, and in the right frontal and temporal area. Patients with left temporal-lobe excisions did not demonstrate a significant deficit. These findings are in agreement with research on non-human primates suggesting that structures in the superior temporal gyrus are important in retaining auditory information over short time spans, and further indicate that the human right temporal area is specialized for this function.

Adolescent↗
PubMed2000

Dendritic cytoskeletal protein expression in mental retardation: an immunohistochemical study of the neocortex in Rett syndrome.

Many syndromes associated with mental retardation (MR) are characterized by cortical dendritic anomalies. Despite their morphological similarity, these changes appear to involve different stages of dendritic development. The neuronal cytoskeleton, which includes microfilaments, neurofilaments and microtubules, is essential for these developmental processes. Levels and phosphorylation of microtubule-associated proteins (MAPs), which stabilize microtubules, seem to determine different stages of dendritic formation with certain MAPs (e.g. MAP-2) appearing to mediate the effects of external modulators upon these processes. Early studies on neuronal cytoskeleton in MR, which have shown a selective reduction in MAP-2 expression, have focused on Rett syndrome (RS). Here, by a semiquantitative immunohistochemical analysis of the pericentral cortex, we examine the contribution of specific neuronal populations to these changes in cytoskeletal proteins. Decreased MAP-2 staining in RS was more marked in layers V-VI, while increased nonphosphorylated neurofilament immunoreactivity was found in layers II-III in RS. Age-related increases in dendritic MAP-2 immunoreactivity in layers V-VI were also absent in RS. The specificity of these cytoskeletal protein changes, their significance for RS pathogenesis and plasticity, as well as their implications for other MR-associated disorders, are also discussed.

Adolescent↗
PubMedDate not supplied

Scheduling of monoaminergic neurotransmitter receptor expression in the primate neocortex during postnatal development.

Quantitative in vitro autoradiography was used to study the postnatal development of monoaminergic receptors (D1 and D2 dopaminergic, 5-HT1 and 5-HT2 serotonergic, and alpha 1, alpha 2, and beta noradrenergic sites) in the prefrontal, primary motor, somatosensory, and visual cortex of rhesus monkeys at birth and 1, 2, 4, 8, 12, 36, and 60 months of age. The density of all receptors studied increased rapidly within the first 2 postnatal months to levels as high as two times that recorded in the adults. After the fourth month, receptor density began a decline that subsided around the time of puberty. This course of developmental change was similar in all cortical layers and in all regions examined. However, the magnitude of the transient overproduction and eventual reduction in receptor density varied across the cortical layers and cytoarchitectonic areas in a manner specific to the individual receptor sites. Overall, cortical maturation was associated with the increased tendency of monoaminergic receptors to concentrate preferentially in the superficial cortical layers. The common developmental course of monoaminergic receptors in diverse cytoarchitectonic areas reveals an impressive coordination in the expression and regulation of these functionally relevant proteins in the cerebral cortex during infancy and adolescence.

Aging↗
PubMedDate not supplied

Regenerative activity in apical dendrites of pyramidal cells in neocortex.

In intracellular recordings from three neocortical pyramidal cells in vitro, intracellular dye injection identified the impalement site as the primary trunk of the apical dendrite. Dendritic recordings displayed two types of regenerative events: relatively fast, low-threshold spikes with amplitudes of 12-69 mV, and slower, higher-threshold spikes up to 80 mV in amplitude. This distinctive dendritic firing pattern was also encountered in six recordings without dye-filled electrodes. Fast spike frequency was extremely sensitive to small changes in membrane potential at the recording site. In one recording, the fast spikes were blocked by 1 microM TTX, while slow events were spared. A computational model of a pyramidal cell was constructed to assist in interpreting the recordings. Simulations suggested that the fast spikes were generated primarily by active Na+ conductance concentrated at a distance from the impalement site, probably in the region of the soma. The low threshold of the fast spikes suggested that Na+ channels also exist in the apical dendrites, where they have a relatively low density. The data strongly imply that there are Ca2+ channels in the apical dendrites.

Action Potentials↗
PubMedDate not supplied

Organization of rodent auditory cortex: anterograde transport of PHA-L from MGv to temporal neocortex.

In the present study we analyzed the organization of the thalamocortical projections of the specific auditory relay nucleus of the thalamus, the ventral division of the medial geniculate body (MGv), using the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin. All injections of MGv produced dense labeling of axonal fibers in temporal cortex. In all cases, labeled axons were predominantly concentrated in cortical layers III and IV and, to a lesser extent, at the junction of layers V and VI. Injections confined to the medial regions of MGv, and specifically to the ovoid nucleus of MGv (OV, pars ovoidea), resulted in anterograde labeling of TE1, with minor labeling of the ventral quarter of TE1, designated subarea TE1v. Injections placed in lateral regions of MGv and occupying the lateral ventral subnucleus (LV), or injections in the mediolateral center of MGv and occupying parts of LV and OV, also resulted in labeling of area TE1 and minor labeling of TE1v. However, these injections also produced labeling in areas TE2 and TE3. Thus, area TE1 (excluding subarea TE1v) receives heavy projections from all aspects of MGv and appears to be the core target of MGv. While regions of MGv also project to surrounding cortical belt areas, these projections tend to be lighter and to vary depending on the region of MGv examined. These results, together with other connectional findings, and cytoarchitectonic and physiological studies, suggest that TE1 (possibly excluding subarea TE1v) is the primary auditory cortex in the rat.

Animals↗
PubMedDate not supplied

Calcitonin gene-related peptide (CGRP) in the cat neocortex: evidence for a sparse but widespread network of immunoreactive fibers.

The morphology, and laminar and topographic distribution of fibers containing calcitonin gene-related peptide (CGRP) immunoreactivity were studied by light and electron microscopic methods in the cerebral cortex of adult cats using a rabbit antiserum raised against the C-terminal region of the rat alpha-CGRP. At the light microscopic level, a sparse number of CGRP-positive fibers were observed in the frontal, parietal, and occipital cortices. They showed numerous irregularly spaced varicosities, were mostly oriented vertically, and in rare cases gave rise to boutons terminaux as they ascended toward the pial surface. At the border between layers I and II, they branched into horizontal fibers that could be followed for several hundred microns in layer I and gave rise to terminal clusters of boutons. In some sections, CGRP-positive fibers were seen in close association with blood vessels. At the electron microscopic level, CGRP immunoreactivity was found in axon terminals containing few mitochondria and clear synaptic vesicles. CGRP-positive axon terminals were very sparse, and mainly of small size. The majority formed conventional synapses, all of the asymmetric type. CGRP-positive fibers showed an uneven topographic distribution through the cortical mantle, with the frontal areas exhibiting the highest density and the occipital cortex the lowest. These results show that CGRP-containing axons are more widely distributed than previously thought since they were observed in all the cortical areas examined, and cast some doubts on the hypothesis that the functional role of this peptide is restricted to the processing of visceral sensory information.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗