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PubMed1995

Temporal pattern of internucleosomal DNA fragmentation in the striatum and hippocampus after transient forebrain ischemia.

Transient forebrain ischemia in rodents caused internucleosomal DNA fragmentation that appeared in the striatum 24 h after reperfusion, and in the hippocampus 72 h after reperfusion. Gel electrophoresis and an in situ technique to label 3' termini of endonuclease generated DNA fragments demonstrated similar temporal patterns. These data show that endonuclease activation accompanies the demise of selectively vulnerable neurons following transient forebrain ischemia.

Animals↗

PubMed1996

Development of GABA and calcium binding proteins immunoreactivity in the rat hippocampus following neonatal anoxia.

The consequences of neonatal anoxia (N2 100% for 25 min at 30 h after birth) on the rat hippocampus were studied 7-60 days postnatally with immunocytochemistry for gamma-aminobutyric acid (GABA), parvalbumin (PV) and calbindin-D28k (CB). In both sham-treated and anoxic rats, GABA immunoreactivity presented a mature expression since early stages, while PV and CB immunoreactivity showed a major postnatal development. In anoxic animals, a significant reduction in the number of hippocampal GABA-immunoreactive neurons was observed at all time-points analysed, a transitory effect on PV immunoreactivity was seen at P7 and P21, while no modifications in the number of CB-immunoreactive neurons could be found. Thus, selective vulnerability of GABA-containing neurons and relative resistance of neurons in which PV or CB immunoreactivity is present or is expressed later, occur in the hippocampus after neonatal anoxia. The role of calcium binding proteins (CBP) in nerve cell protection is discussed.

Animals↗

PubMed1996

Lewy bodies are located preferentially in limbic areas in diffuse Lewy body disease.

Lewy bodies (LBs)are found throughout the brain stem, limbic and neocortical areas in Parkinson's disease. Lewy bodies are also associated in these areas with dementia and the substrate of 'dementia with Lewy bodies' is thought to include Lewy body pathology in limbic and neocortical areas with or without Alzheimer-type changes. In order to determine whether dementia with Lewy bodies is characterised primarily by cortical or limbic LB pathology, we have measured the density of Lewy bodies, neuritic plaques and neurofibrillary tangles in 12 neocortical, limbic and brain stem sites in 10 patients who were pathologically diagnosed with diffuse Lewy body disease (DLBD) (64.7 +/- 2.7 years). The mean LB density in limbic areas (3.00 +/- 0.61/mm2) was significantly greater than that of neocortical areas (1.13 +/- 0.22/mm2, P < 0.001). The greatest density of LBs was found in the amygdala (4.1 +/- 0.7/mm2) and the lowest in the occipital cortex (0.3 +/- 0.1/mm2). In limbic areas, LB formation positively correlated with neuritic plaque formation (r = 0.51, P < 0.01) but not with neurofibrillary tangle densities. These data indicate that dementia with Lewy bodies is characterised primarily by limbic, and secondly by neocortical, LB pathology. It remains to be determined why limbic areas are selectively vulnerable to LB pathology in dementia with Lewy bodies.

Aged↗

PubMed1982

A bioenergetic basis for peripheral nerve fiber dissociation.

The selective vulnerability of myelinated axons in lesions of peripheral nerve is incompletely understood and appears somewhat at variance with the energy conservation attached to saltation in these fibers. We evaluated the relative energy requirement of resting A and C fibers in rabbit vagus nerve by measuring the amplitude of the components of the compound action potential at 5-10 min intervals during incubation in Ringer-bicarbonate solutions containing 0-20 mM glucose. In nerves in which the perineurial sheath was retained intact the A components remained at control amplitude with 20 mM glucose but, after a plateau period, declined increasingly rapidly with 5, 2, 1, 0.5 and 0 mM glucose. 2mM glucose sufficed to maintain control amplitude of the C fiber component. In desheathed nerves the A component remained at control amplitude with 5 mM glucose but declined increasingly rapidly with 2, 1, 0.5 and 0 mM glucose; 0.5 mM glucose sufficed to maintain control amplitude to C fibers. The depressed potentials generally recovered incompletely after transfer to glucose 5 mM (desheathed) or 20 mM (sheathed); however, the partial recovery was more rapid and more nearly complete in the C fiber group than in the A fiber group (P less than 0.05). The data demonstrate that resting A fibers are much more susceptible to energy lack in vitro than resting C fibers. This suggests that deprivation of energy may be a factor in the preferential destruction of large fibers, termed fiber dissociation, which characterized several syndromes of chronic pain.

Action Potentials↗

PubMed1990

Responses of cells of the rat fascia dentata to prolonged stimulation of the perforant path: sensitivity of hilar cells and changes in granule cell excitability.

Recent studies have shown that prolonged stimulation of afferents of the rat fascia dentata in vivo leads to the development of chronic epileptiform activity of the dentate granule cell region, and degeneration of certain cell types in the adjacent hilus. To investigate the development of dentate hyperexcitability and the selective vulnerability of hilar cells, the hippocampal slice preparation offers an in vitro model in which cellular mechanisms can be examined. We have recorded intracellularly from granule cells and hilar cells in tissue slices from rat before, during, and following sustained stimulation of the major afferent input to the dentate gyrus, the perforant path. Results from intracellular studies in slices were consistent with in vivo studies. Hilar cells were far more sensitive to short-term or prolonged perforant path stimulation than granule cells. At a time when the granule cell population response was not affected by prolonged stimulation, simultaneous recordings from hilar cells and some granule layer interneurons showed that these cells were already depolarized, had very low input resistance, and showed other electrophysiological changes indicative of deterioration. In contrast, granule cells generally hyperpolarized during stimulation and their input resistance increased; no signs of injury were evident in granule cells. Some stimulus-induced changes in the physiological characteristics of granule cells, such as decreased spike frequency adaptation and reduced inhibitory postsynaptic potentials, may contribute to the development of dentate hyperexcitability.

Animals↗

PubMed1990

Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death.

We investigated the pathogenic role of free radical formation in ischemic neuronal death using radical scavenger, superoxide dismutase. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. The effects of free superoxide dismutase and a derivatized superoxide dismutase, pyran copolymer conjugated superoxide dismutase, on early ischemic damages, detected sensitively by the immunohistochemical reaction for microtubule associated protein 2, and a subsequent delayed neuronal death after restoration of blood flow were investigated. Preischemic treatment by pyran conjugated superoxide dismutase showed clear protective effects against both the neuronal damages detected by immunohistochemistry after 5 min ischemia and the delayed neuronal necrosis after one week of recovery, although no clear beneficial effects were observed when this drug was administered just before the recirculation or free superoxide dismutase was used. These results strongly suggest that free radical generation during brief period of ischemia plays a pivotal role in triggering the ischemic neuronal damages causing delayed neuronal death at the selectively vulnerable areas of the brain.

Animals↗

PubMed1992

The neurofilament triplet is present in distinct subpopulations of neurons in the central nervous system of the guinea-pig.

It is commonly assumed that most, if not all, neurons contain the intermediate filament protein class known as the neurofilament protein-triplet. The following study investigated the distribution of neurofilament protein-triplet immunoreactivity in selected regions of the guinea-pig central nervous system using monoclonal antibodies directed against phosphorylation-independent epitopes on the three subunits under optimal tissue processing conditions. Neurofilament protein-triplet immunoreactivity was present in distinct subpopulations of neurons in the cerebellar cortex, neocortex, hippocampal formation, retina, striatum and medulla oblongata. In many of these regions, labelled neurons represented only a small proportion of the total. The selective distribution of this intermediate filament protein class was confirmed in double-labelling experiments using antibodies to the neurofilament protein-triplet in combination with antibodies to other neuronal markers. The distribution of neurofilament protein-triplet immunoreactivity also correlated with the distribution of staining observed with a silver impregnation method based on Bielschowsky. The present results in combination with previous observations have demonstrated that the neurofilament protein-triplet is found in specific subclasses of neurons in different regions of the nervous system. Content of this intermediate filament protein class does not appear to be correlated with neuronal size or length of projection. These results also suggest that the selectivity of staining between neuronal classes observed with classical silver impregnation methods may be due to the presence or absence of the neurofilament protein-triplet. The present results may also provide a new perspective on the basis of the selective vulnerability of neurons in degenerative diseases.

Animals↗

PubMed1993

Selective neuronal death in the contralateral hippocampus following unilateral kainate injections into the CA3 subfield.

Intracerebral or intraperitoneal injections of kainic acid, an agonist at a class of glutamate receptors, have been extensively used to model temporal lobe epilepsy. In the present study we compared the types and distributions of selectively vulnerable neurons in the ipsi- and contralateral hippocampi following unilateral kainate injections into the CA3 subfield in order to examine whether "proximal" or "distant" neuronal damage resembled the pathology, and possibly also the mechanism, of human temporal lobe epilepsy. The degeneration of principal cells in the different hippocampal subfields was visualized by silver impregnation, and the loss of various types of non-principal cells was studied by immunostaining for the calcium binding proteins parvalbumin, calbindin-D28k and calretinin, as well as for somatostatin. In the first series of experiments various concentrations (ranging from 0.1 to 1 mg/ml) and volumes (0.5-2 microliters) of kainate were tested to induce reproducible damage in the contralateral hippocampus. The optimal dose, employed in the subsequent vulnerability studies, was found to be 3 x 0.5-microliter injections (over a period of 10 min) of a concentration of 0.33 mg/ml under ether anaesthesia, which was discontinued immediately after injection. Anaesthesia with equithesin was found to prevent contralateral cell death. Most if not all pyramidal cells in the CA3 region degenerated on the ipsilateral side, whereas the dentate granule cells, and the majority of CA1 pyramidal cells were resistant. A strikingly different pattern was found on the contralateral side, where CA1 pyramidal cells were almost completely lost, but the CA3 region (with the exception of CA3c) and the dentate gyrus remained intact. Three subpopulations of non-principal cells were found to be vulnerable in both hemispheres, the hilar somatostatin cells, spiny calretinin cells and mossy cells, as well as the spiny calretinin cells in stratum lucidum of CA3. The other subpopulations were resistant, except for those within the effective injection site. We propose that the "distant" (contralateral) damage resembles the pattern, and probably also the mechanism, of cell death in human temporal lobe epilepsy, whereas the ipsilateral damage does not.

Anesthetics↗

PubMed1995

Differential regulation of catalytic and non-catalytic trkB messenger RNAs in the rat hippocampus following seizures induced by systemic administration of kainate.

Ribonuclease protection analysis and quantitative in situ hybridization histochemistry were used to investigate the coordination and regional expression of catalytic and non-catalytic trkB messenger RNAs in the adult rat hippocampus following systemic kainate-induced seizures. Changes in trkB expression were compared with the messenger RNA expression of its neurotrophic ligands, brain-derived neurotrophic factor and neurotrophin-3. TrkB messenger RNA expression was increased in the dentate granule cells at 1-4 h following the onset of seizures, and returned to control levels 16-24 h thereafter. In addition, seizures also induced expression of trkB messenger RNA in putative non-neuronal cells at four to seven days in the molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1 region. Hybridization with probes specific for the non-catalytic trkB receptor and the catalytic trkB receptor revealed that the increases at four and seven days in the molecular layers of the hippocampus reflected an up-regulation of only the non-catalytic form of the receptor. Furthermore, the neuronal increases observed 1-4 h were due to an up-regulation of both trkB TK- and trkB TK+ messenger RNAs. It was established that systemic administration of kainate increased brain-derived neurotrophic factor messenger RNA levels in the pyramidal and granule cell regions of the hippocampus 1-4 h following the onset of behaviorally manifested seizure activity. Early changes in neuronal expression of trkB TK- and trkB TK+ messenger RNA paralleled changes in brain-derived neurotrophic factor messenger RNA in the dentate granule cell and CA1 pyramidal cell layers, but not in the CA3 subregion. These data suggest that concomitant regulation of brain-derived neurotrophic factor and its cognate receptor may play a role in the selective vulnerability of hippocampal subregions to kainate-induced neuropathology. Furthermore, these data suggest a dual function for trkB receptor expression in the hippocampus following kainate-induced seizures, possibly related to both the plastic and degenerative consequences of seizure induction by kainate.

Animals↗

PubMed1994

Cortical neurons containing calretinin are selectively resistant to calcium overload and excitotoxicity in vitro.

Calbindin and the more recently identified protein calretinin are structurally related calcium-binding proteins having a broad distribution in the brain. Recent evidence supports a neuroprotective role for calbindin in regulating calcium homeostasis during periods of heightened Ca2+ influx. It is not known if calretinin might have a similar function. We investigated if calretinin-containing neurons have a survival advantage in rat neocortical cultures treated with a calcium ionophore or excitatory amino acids. Neuronal cultures were challenged with the calcium ionophore A23187 at different concentrations to produce a broad range of cell death. Cell loss was quantified for both the calretinin immunopositive and the calretinin immunonegative populations of neurons. We found that 3 h after exposure to 2 microM A23187 there was a 48% loss of the calretinin immunonegative population of neurons whereas the calretinin immunopositive set of neurons was reduced by only 18%. Calretinin positive neurons were still relatively spared after treatment with 3 microM A23187. The ionophore had no cytotoxic effect when calcium ions were removed from the extracellular medium. We also studied glutamate excitotoxicity by treating the neuronal cultures with the excitatory amino acids glutamate, N-methyl-D-aspartate or kainate for 5 min and examining survival three hours later. We found again that calretinin-containing neurons were relatively spared after exposure to the excitatory amino acids; at doses of N-methyl-D-aspartate and kainate that produced a 32-40% loss of calretinin immunonegative neurons, only 2-10% of calretinin immunopositive neurons died. Similar results were obtained for glutamate. These results demonstrate that neurons containing calretinin are better able to survive disturbances in calcium homeostasis than cells not containing this calcium-binding protein. The fact that this effect was observed with ionophore treatment, as well as excitatory amino acids, suggests that neither the density nor distribution of glutamate receptors on the different cell types was a factor in determining selective vulnerability. We hypothesize that the neuroprotective effect of calretinin is due to the buffering capacities of the protein in a manner analogous to that suggested for calbindin.

Animals↗

PubMed1996

Cyclin D1 messenger RNA is induced in microglia rather than neurons following transient forebrain ischaemia.

Following 30 min of forebrain ischaemia in the rat, delayed neuronal death occurs in the CA1 sector of the hippocampus within two to three days, whereas neurons in other selectively vulnerable regions, such as the dorsolateral striatum, die within 6-12 h. In this study, we investigated cyclin D1 expression, which codes for a regulatory protein in cell cycle regulation, but it is also induced in sympathetic neurons undergoing programmed cell death. Cyclin D1 messenger RNA could not be detected by in situ hybridization techniques in brains of control rats, but was found at one and two days after ischaemia in regions of the dorsolateral striatum with neuronal degeneration. DNA fragmentation in this region, identified by the terminal transferase biotinylated-UTP nick end labelling (TUNEL) procedure, was observed from 6 h after ischaemia onward. In the hippocampus, increased levels of cyclin D1 messenger RNA were found at two and three days after ischaemia in the striatum pyramidale of the CA1 sector. This expression was associated with the occurrence of neuronal damage and TUNEL-stained neurons. By seven days cyclin D1 messenger RNA was found in hardly any brain structure. There was no temporospatial overlap of cyclin D1 expression with the expression of the immediate-early genes c-fos, c-jun, and mkp-1, a result which is clearly distinct from findings in sympathetic ganglion neurons undergoing programmed cell death. These results do not suggest a role for cyclin D1 in neuronal cell death following transient forebrain ischaemia. The similarity of the cyclin D1 expression profile with that of the microglia-specific CR3 complement receptor beta-subunit messenger RNA, and the results of combined in situ hybridization and microglia-specific immunohistochemistry suggest that microglia are the source of cyclin D1 messenger RNA in the postischaemic brain. Since cyclin D1 codes for a critical regulatory protein for progression of the G0 to G1 phase in the cell cycle and we did not observe prominent occurrence of DNA fragmentation in microglial cells in the hippocampus at time points when cyclin D1 messenger RNA was found, we suggest that cyclin D1 induction is involved in the onset of microglial cell proliferation.

Animals↗

PubMed1996

An immunocytochemical study of the distribution of AMPA selective glutamate receptor subunits in the normal human motor system.

Glutamate is the major mediator of fast excitatory neurotransmission in the mammalian central nervous system. Disturbances of this neurotransmitter system have been implicated in chronic degenerative neurological disease. Recently, major advances in our knowledge and understanding of the molecular biology of the glutamatergic receptor system have been made. It is now known that functional glutamate receptors consist of various combinations of some 20 identified subunits. A growing body of circumstantial evidence suggests that the non-N-methyl-D-aspartate subtype of glutamate receptors may mediate, at least in part, the selective motor neuron death seen in the human neurodegenerative disease amyotrophic lateral sclerosis. We have used subunit specific immunocytochemistry to study the distribution and potential subunit composition of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) selective glutamate receptors, (a subgroup of non-N-methyl-D-aspartate selective glutamate receptors formed by combinations of GluR1-4 subunits), in the human motor system. Motor neurons in the spinal cord, brainstem, and motor cortex were relatively strongly immunoreactive with the GluR2/3 subunit antibody, moderately so with the GluR4 subunit antibody, and showed relatively low levels of immunoreactivity with the GluR1 subunit antibody. This is the first detailed study of AMPA receptor subunit expression in the human motor system. Motor neurons express a distinct subunit profile when compared with other groups of neurons in the human nervous system. There were no significant differences in the pattern of relative AMPA subunit expression (GluR2/3 > or = GluR4 > GluR1) between groups of motor neurons typically affected (in the spinal cord and hypoglossal nucleus), or spared (oculomotor and Onufs nucleus) by the amyotrophic lateral sclerosis disease process. However, oculomotor motor neurons had higher levels of expression of all AMPA subunit proteins which may indicate greater AMPA mediated glutamatergic input in the normal function of this neuronal population. This study does not support a role for differential subunit composition of AMPA receptors in determining the selective vulnerability of motor neurons in amyotrophic lateral sclerosis. However, the overall density of receptors may be of importance.

Aged↗

PubMed1990

Peptides in the neocortex in Alzheimer's disease and ageing.

Studies which have examined neuropeptides in Alzheimer's disease (AD) and normal ageing are reviewed. A marked specificity and selectivity is noted: most neuropeptides are normal, and the only two peptides consistently altered are somatostatin (SRIF) and corticotropin releasing hormone (CRH). Binding sites for CRH are increased in number in a reciprocal fashion to the reduction in CRH. These findings (1) provide evidence for selective vulnerability within the cortex in AD, (2) suggest that the primary site of pathology in AD may be cortical, and (3) indicate that the pathological process of AD is distinct from that of normal ageing.

Aging↗

PubMed1985

Perinatal glucocorticoids alter dentate gyrus electrophysiology.

Perinatal glucocorticoid administration produces permanent spatial discrimination learning deficits in rats, presumably referable to changes in the development of neural systems subserving such functions. Because the hippocampal dentate gyrus and its afferent/efferent circuitry appear selectively vulnerable to neonatal steroid treatments, we have examined adult rats treated with neonatally administered glucocorticoids using electrophysiological methods. The techniques were chosen to reveal the topographic and neurophysiologic responsiveness of the major afferent supply to the dentate gyrus. Rats of both sexes received either a high dose (100 mg/kg) or low dose (1 mg/kg) of the synthetic glucocorticoid dexamethasone on postnatal day four, with control subjects receiving an injection of saline. These dosages have been shown to disrupt hippocampal dependent learning [6,38]. Laminar depth profile analyses of entorhinal cortex-dentate gyrus afferents revealed a significant shift in the spatial distribution of evoked extracellular population synaptic potentials (EPSPs) in glucocorticoid treated subjects. Stimulus-response functions also differed between glucocorticoid treated and control subjects. While response amplitudes at threshold stimulus intensities did not differ between groups, at higher stimulus intensities population spike potentials and associated EPSPs differed in glucocorticoid versus control subjects.

Animals↗

PubMed1983

An active process in cochlear mechanics.

A model for cochlear mechanics is proposed to take account of its two systems, one passive and one active. The classical passive system stimulates the inner hair cells directly at levels above about 40 dB SL. At intensities below about 60 dB an active process, the 'cochlear amplifier' (CA), somehow provides additional energy that enhances the vibration of a narrow segment of the basilar membrane near the apical foot of the familiar, traveling wave envelope. The outer hair cells are essential for CA. The active system acts like a high-Q acoustic resonator, and it accounts for the great sensitivity and sharp tuning expressed by the 'tips' of neural tuning curves. The tips are selectively vulnerable to anoxia, noise exposure and other trauma. The CA model explains the detection of small differences in time as well as in frequency, the dual character of the electrocochleogram, recruitment of loudness in cochlear hearing impairment, the long latency of normal neural responses near threshold, acoustic emissions (both stimulated and spontaneous) and the locus of TTS in the frequency range above the exposure tone. Both the classical high-intensity system and the active low-level CA system are highly nonlinear and they combine to compress the great dynamic range of hearing into a much narrower range of mechanical movement of the cilia of the inner hair cells. The mechanism of CA is unknown, and the problem remains of how its action can be triggered by submolecular movements near threshold.

Auditory Threshold↗

PubMed1986

Experimental maternal hyperpipecolatemia decreases DNA in the mouse brain.

Pipecolic acid represents the major metabolite of lysine in the CNS. This study aimed to mimic the known pathological condition of hyperpipecolatemia in human neonates by maintaining high and steady concentrations in the mouse brain both pre- and postnatally. Although histological observations did not reveal any abnormal findings in the brain, liver and kidney, the offsprings of mothers which were injected during pregnancy with 250 mg/kg PA presented a significant decrease in both cortical and whole brain DNA content. Protein, RNA and CNPase activity were not altered. The changes in DNA content are of particular interest since they demonstrate that a high and steady level of pipecolic acid, which is comparable to the level seen in human hyperpipecolatemic brain, can induce a neurotoxic effect in the fetal mouse brain. Mice injected with the same dose from day 1 to day 29 after birth did not show any change in DNA content in the cortex. These results suggest that the critical period from pipecolic acid neurotoxic effect is prenatal, probably due to a selective vulnerability of developing neurons to high levels of pipecolic acid. The decrease in DNA concentration induced by maternal hyperpipecolatemia suggests a neurotoxic effect of pipecolic acid on cell proliferation during fetal development which could be related to the neuronal damage observed in the brain of hyperpipecolatemic neonates.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed1992

Effects of pentylenetetrazol-induced seizures on dopamine and norepinephrine levels and on glucose utilization in various brain regions of the developing rat.

Levels of dopamine and norepinephrine were measured in seven brain areas after 60 min of sustained seizure activity induced by intraperitoneal repetitive timed administrations of pentylenetetrazol in rats at 10, 14, 17 and 21 days of postnatal life. The tissue levels of norepinephrine were markedly reduced in the majority of brain structures, except for striatum at 10 and 14 days. Conversely, dopamine concentrations increased in many areas and at various ages, except in cerebral cortex at 10 and 14 days and in midbrain between 14 and 21 days. PTZ seizures induced marked increases over control levels in the rates of glucose utilization, measured by the quantitative autoradiographic [14C]2-deoxyglucose method, in all dopamine- and norepinephrine-innervated areas studied at 10 and 14 days, except in cerebellar cortex at both ages and in frontal cortex and anteroventral thalamus at 14 days. At 17 and 21 days, glucose utilization remained increased over control levels in some areas, mainly in catecholaminergic cell groupings such as substantia nigra, ventral tegmental area and locus coeruleus, but was significantly reduced in cortex, caudate nucleus and thalamus, and similar to control rates in other regions. The present results suggest that pentylenetetrazol-induced seizures lead to a simultaneous increase in functional activity of norepinephrine neurons and an inhibition of dopaminergic-mediated neurons. They also confirm the maturation of connections, of metabolic activity and of neurotransmitter interaction within the brain, occurring mainly during the third week of postnatal life, paralleled by an increased selective vulnerability of some regions to this kind of insult.

Animals↗

PubMedDate not supplied

Neurochemical alterations but not nerve cell loss in aged rat neostriatum.

Numerical changes in the overall neostriatal neuronal population have been investigated by morphometric analysis of Nissl-stained and glucocorticoid receptor-immunoreactive neurons. Number and staining intensity of various chemically-identified nerve cell populations were analysed by means of immunocytochemistry coupled with computer-assisted image analysis. Three- and 24-month-old male Sprague-Dawley rats were used. No change in the number of Nissl-stained, glucocorticoid receptor-, dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein- and enkephalin-immunoreactive neurons and a 50% decrease of neuropeptide Y-immunoreactive neurons were observed in the aged rat. In our preparations, the glucocorticoid receptor antibody stains around 90% of the neostriatal neurons, the dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein and enkephalin antibodies label 25-35% and the neuropeptide Y antibody stains only 1% of neostriatal neurons. In the same preparations a significant decrease in the intensity of immunostaining was observed for enkephalin-, dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein- and neuropeptide Y-immunoreactive neuronal cell bodies and tyrosine hydroxylase-immunoreactive nerve terminals in the aged rat. In the case of neuropeptide Y- and dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein-immunoreactive neurons, the changes in the intensity of immunostaining were differentially compartmentalized within neostriatum, suggesting selective vulnerability of striatal subregions to ageing processes. In conclusion, these data indicate that no significant age-related neuronal cell loss occurs in neostriatum. On the other hand, a generalized decrease in the levels of peptide transmitters and molecules related to dopamine transmission is observed in aged rat neostriatum, possibly resulting in the known age-related deficits of neostriatally-controlled behaviours.

Aging↗