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Biomedical subjects

C Nyakas

Publications and source records attributed to C Nyakas.

At least 73 records · Page 4Linked to original sources

Behavioral and biochemical effects of early postnatal cholinergic lesion in the hippocampus.

The effects of early postnatal (PD 8) intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A) on development of open-field and cognitive behaviors and cholinergic markers in several brain areas were examined in the rat. The cholinotoxin was bilaterally administered in a dose range of 0.25 to 2.0 nmol. In the open-field tests, the cholinergic lesion caused a dose-dependent increase in activity at 20 days of age, while it resulted in lengthened latency to initiate exploration and decreased rearing activity at adulthood. Hole-board spatial learning was severely inhibited in adult age. The biochemical activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the hippocampus was markedly decreased in a dose-dependent manner, but was unchanged in the neocortex and striatum. Histochemical staining of AChE-positive fibers revealed a severe cholinergic denervation of the granular and pyramidal cell layers of the hippocampus. The results showed that a selective cholinergic deafferentation of the hippocampus at a critical stage of development leads to long-lasting abnormal open-field and spatial learning behaviors.

Acetylcholinesterase↗

Effects of neonatal administration of vasopressin on cardiac and behavioral responses to emotional stress in adult male rats.

Arginine-8-vasopressin (AVP) was administered subcutaneously on postnatal days 3-7 in a high (10 micrograms/100 g b.wt.) or a low dose (1 microgram/100 g b.wt.) to male Wistar rats. Control pups were untreated or saline injected. Behavioral observations in a complex maze after maturation indicated that neonatal administration of AVP increases exploratory behavior in this novel environment in a dose-dependent way. Cardiac monitoring during the conditioned emotional stress of fear of inescapable electric footshock showed that only the high dose of AVP attenuates the bradycardiac stress response. The analysis of cardiac responses also suggested an adult hyposensitivity to AVP in rats treated neonatally with AVP. In addition, the low dose of neonatal AVP was impairing the retention of a passive avoidance behavior. The data indicate that the neonatal administration of AVP exerts long-term effects upon the behavioral adaptation to novelty and memory processes related to emotional stress. That neonatal AVP is less effective in influencing adult vagally mediated cardiac stress responses suggests differences in the developmental sensitivity ("critical periods") of the central vasopressinergic systems involved in the regulation of behavior and autonomic functioning.

Animals↗

Protective effect of the calcium antagonist nimodipine on discrimination learning deficits and impaired retention behavior caused by prenatal nitrite exposure in rats.

Discrimination learning behavior and retention of a passive avoidance response were studied in male adult offspring of gestating rats exposed to drinking water containing 2 g/l sodium nitrite, throughout the second half of pregnancy. Both in an auditory and visual discrimination learning paradigm NaNO2-exposed rats were inferior to controls. The long-term retention of a passive avoidance response was also impaired. The acquisition of simple learning tasks was not significantly disturbed. The concomitant prenatal daily treatment with the calcium antagonist nimodipine in a dose of 10 mg/kg p.o. interfered with the nitrite neurotoxicity and prevented the development of adult behavioral deficits. The results support the hypothesis that Ca2+ homeostasis of neurons is an important factor for normal development of brain and behavior.

Animals↗

Cortical projection patterns of the medial septum-diagonal band complex.

A detailed analysis of the cortical projections of the medial septum-diagonal band (MS/DB) complex was carried out by means of anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). The tracer was injected iontophoretically into cell groups of the medial septum (MS) and the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and sections were processed immunohistochemically for the intra-axonally transported PHA-L. The labeled efferents showed remarkable differences in regional distribution in the cortical mantle dependent on the position of the injection site in the MS/DB complex, revealing a topographic organization of the MS/DB-cortical projection. In brief, the lateral and intermediate aspects of the HDB, also referred to as the magnocellular preoptic area, predominantly project to the olfactory nuclei and the lateral entorhinal cortex. The medial part of the HDB and adjacent caudal (angular) part of the VDB are characterized by widespread, abundant projections to medial mesolimbic, occipital, and lateral entorhinal cortices, olfactory bulb, and dorsal aspects of the subicular and hippocampal areas. Projections from the rostromedial part of the VDB and from the MS are preponderantly aimed at the entire hippocampal and retrohippocampal regions and to a lesser degree at the medial mesolimbic cortex. Furthermore, the MS projections are subject to a clear mediolateral topographic arrangement, such that the lateral MS predominantly projects to the ventral/temporal aspects of the subicular complex and hippocampus and to the medial portion of the entorhinal cortex, whereas more medially located cells in the MS innervate more septal/dorsal parts of the hippocampal and subicular areas and more lateral parts of the entorhinal cortex. PHA-L filled axons have been observed to course through a number of pathways, i.e., the fimbria-fornix system, supracallosal stria, olfactory peduncle, and lateral piriform route (the latter two mainly by the HDB and caudal VDB). Generally, labeled projections were distributed throughout all cortical layers, although clear patterns of lamination were present in several target areas. The richly branching fibers were abundantly provided with both "boutons en passant" and terminal boutons. Both distribution and morphology of the labeled basal forebrain efferents in the prefrontal, cingulate, and occipital cortices closely resemble the distribution and morphology of the cholinergic innervation as revealed by immunohistochemical demonstration of choline acetyltransferase. In contrast, the labeled projections to the olfactory, hippocampal, subicular, and entorhinal areas showed a heterogeneous morphology. Here, the distribution of only the thin varicose projections resembled the distribution of cholinergic fibers.

Animals↗

Age-related alterations in cardiac response to emotional stress: relations to behavioral reactivity in the rat.

Age and behavioral characteristics are considered as risk factors for disturbances of the cardiac rhythm. Emotional stress may be a disseminating factor. Therefore, cardiac responsiveness and behavioral reactivity and their relation as a function of age have been studied in the rat. Young (3-month-old) and young adult (5-month-old) rats display a relative deceleratory cardiac response with bradyarrhythmias in the initial phase of response to emotional stress evoked by stimuli associated with a previous painful experience. The behavioral response is immobility. The immobility response is also displayed by aged (21-month-old) and senescent (33-month-old) rats but the initial bradycardiac heart response to emotional stress is absent, and the incidence of repetitive extrasystoles is increasing with age. An inverse correlation between behavioral reactivity to novel stimuli and the bradycardiac heart responsiveness is observed in young and young adult individual animals. The behavioral reactivity of the aged and senescent rats is diminished, but the correlation with cardiac reactivity remains preserved. It is suggested that the behaviorally coupled inhibitory influences on the heart are diminishing during aging either due to impairments in the descending cholinergic (vagal) system or secondarily, due to a decrease in the central "drive" of this system.

Aging↗

Long-term effects of cholinergic basal forebrain lesions on neuropeptide Y and somatostatin immunoreactivity in rat neocortex.

The effect of cholinergic basal forebrain lesions on immunoreactivity to somatostatin (SOM-i) and neuropeptide-Y (NPY-i) was investigated in the rat parietal cortex, 16-18 months after multiple bilateral ibotenic acid injections in the nucleus basalis complex. As a result of the lesion, the cholinergic fiber density in the cortex decreased by 66% with a concurrent increase in SOM-i fibers by more than 50% and a 124% increase in NPY-i fiber innervation. The neuropeptidergic sprouting response on cholinergic denervation does not match the concurrent cholinergic and peptidergic decline in Alzheimer's disease and as such does not support the cholinergic lesion alone as an animal model for this neurodegenerative disorder.

Animals↗

Age-related changes in adrenocorticoid and opioid receptor capacity of thymus-derived lymphocytes in rats.

The experiments were performed in 4-day, 4-week, and 4-month old rats. The total binding capacity of high affinity receptors for 3H-naloxone and 3H-corticosterone in thymus-derived lymphocytes was measured in vitro. There was no change in the affinity constant of the receptors for the ligands during the life-time mentioned before. The maximal binding capacity for 3H-corticosterone in thymus-derived lymphocytes showed a marked increase in 1-month and 4-month old ages as compared to the values obtained by the end of the first postnatal week. In contrast, the maximal binding capacity of lymphocytes for 3H-naloxone showed a significant decline with age. Changes in the binding capacity for the two ligands refer to changes in composition of of cells within the thymus and to alterations in cell system in sensitivity to either corticosteroids or opioids.

Adrenal Cortex Hormones↗

Nitrate induced changes in sensoro-motor development and learning behaviour in rats.

Development of sensoro-motor functions and adult learning behaviour was studied in rats subjected to nitrate exposure. Pregnant and lactating dams and their offspring were supplied with drinking water containing nitrate, 1.12 or 2.24 mM KNO3, and compared with nitrate-free controls. Postnatal maturation of reflexes, that of sensory and somatic parameters and motor activity, furthermore, the acquisition of one-way avoidance and rewarded discriminative learning behaviour in adulthood were examined. Reflexes (righting, cliff-avoidance) and hearing startle reaction maturated earlier in nitrate treated groups. No difference was found in olfactory homing behaviour, in the time of eye opening and in body weight growth. Open-field motor activity was higher at days 5, 7, 10 after birth, but hypoactivity ensued after day 20. A marked learning deficit was observed both in punished and in rewarded learning paradigms. The results indicate a nitrate induced deviation in behavioural development, and an impairment in learning behaviour, particularly of discriminative type.

Animals↗

Hippocampal kindling-induced after-discharge and behavioural depression: immediate and long-term attenuation by opiate antagonists.

Hippocampal kindling results in tonic-clonic convulsions followed by a pronounced period of behavioural depression. The effect of the opiate antagonists, naltrexone and naloxone, on the duration of the after-discharge and behavioural depression was investigated. Naltrexone, injected s.c. 60 min before, significantly reduced the behavioural depression at doses as low as 0.6 mg/kg, but had no effect on the after-discharge even at higher doses. One day later, the behavioural depression was still reduced in some animals and the after-discharge was significantly decreased following the higher doses (0.24-0.48 mg/kg). Naloxone, injected s.c., 10 min before, significantly reduced the behavioural depression at a dose as low as 0.002 mg/kg and also reduced the duration of the after-discharge at some doses. Naloxone did not exert any significant effects 24 h later. Naltrexone, injected i.c. 60 min before kindling in a dose of 1 microgram, significantly attenuated the behavioural depression and had no effect on the after-discharge. The behavioural depression was still attenuated 24 and 48 h later. The involvement of mu-receptor-related endogenous opioid mechanisms in postictal brain processes is suggested. The long-term effects might be related to receptor 'activation' during the immediate period due to an interaction between the antagonist and the kindling experience.

Animals↗

Changes in septo-hippocampal projections after lateral entorhinal or combined entorhinal-raphé lesions as studied by anterograde tracing methods.

Septal and entorhinal projections to the hippocampus show a considerable overlap in their target structures in the molecular layer of the dentate gyrus (DG) and stratum lacunosum-moleculare of the cornu ammonis (CA). Employing anterograde tracing methods, it was investigated in which way the morphological pattern of the septohippocampal projections were influenced by lateral entorhinal cortex (LEA) lesions. Anterograde filling of neurons from soma to axonal terminals with Phaseolus vulgaris leucoagglutinin (PHA-L) revealed lesion-induced changes in innervation patterns in the DG but not in CA fields. LEA lesions provoke an impressive shift of septo-dentate projections from a predominant middle molecular layer innervation to the outer molecular layer, whereas septal projections to the CA remain unchanged. Comparison with concurrent acetylcholinesterase (AChE) staining and immunocytochemical demonstration of choline acetyltransferase (ChAT) confirm the cholinergic nature of this plasticity response. This response was equally strong in unilateral or bilateral damage to the LEA and was neither enhanced nor inhibited by simultaneous injury to the median raphé nuclei.

Acetylcholinesterase↗

Detailed projection patterns of septal and diagonal band efferents to the hippocampus in the rat with emphasis on innervation of CA1 and dentate gyrus.

The detailed patterns of afferentation to the ammon's horn and dentate gyrus of the hippocampus in the rat were investigated employing the anterograde tracer Phaseolus vulgaris leuco-agglutinin (PHA-L) after punctate iontophoretic injections in the medial septum (MS) and vertical limb of the diagonal band of Broca (VDB). The topographically ordered innervation pattern was different in the regio superior (or CA1) vs. the regio inferior (or CA3) and in the dorsal vs. ventral aspects of ammon's horn and dentate gyrus. The CA1 pyramidal and dentate granule cell layers in the dorsal hippocampus received afferent input almost exclusively from the VDB, whereas those cell layers in ventral hippocampus were supplied from both VDB and MS. The PHA-L labeled projecting fibers could be differentiated into two distinct fiber systems. One class of thick and coarse axons (tentatively called type I fibers) carried fewer but larger terminal boutons and were found to infiltrate the entire stratum oriens, dentate hilus, all layers of the regio inferior and the CA1 str. moleculare. A second, delicate thin (type II) fiber system provided with numerous and passant varicosities showed a much more restricted laminar innervation pattern and appeared to originate from areas in MS-VDB which are rich in AChE-positive neurons. The densest type II fiber networks could be observed in the CA1 subpyramidal and dentate supragranular zones, in the CA1 stratum lacunosum-moleculare and in the dentate middle third molecular layer. This laminar type II innervation pattern showed a remarkable coincidence with the reported distribution of cholinergic marker enzymes. The topographic and spatial organization of the projections described above will be discussed in relation to their possible functional significance.

Acetylcholinesterase↗

Corticosteroid receptor plasticity and recovery of a deficient hippocampus-associated behavior after unilateral (dorsal) hippocampectomy.

Unilateral ablation of the right dorsal hippocampus (HCX) produced changes in maximal corticosteroid binding capacity (Bmax) in the contralateral hippocampal lobe of the rat with time. The mechanism by which this time course of changes was produced seemed to involve the pituitary-adrenal system, since a certain difference in corticosteroid receptor binding pattern was noted between chronic adrenalectomized (ADX) rats and rats which remained intact during postlesion survival. In the presence of endogenous adrenal hormones the HCX-induced changes in corticosteroid receptor binding relative to that observed in rats with the overlying neocortex ablated (control) were the following: a 26% decrease at 5 days after HCX; an increase the following 3 weeks with a maximum of 46% at 20 days postsurgery; and recovery towards control values after longer survival times. After discrimination of corticosteroid binding into two corticosterone (CORT) binding receptor populations, e.g. glucocorticoid receptors (GR) and mineralocorticoid-like or CORT receptors (CR), the lesion-induced effect was more pronounced in GR than in CR. A 72% increase over controls was measured at 20 days postsurgery. In the absence of the adrenals, however, the Bmax of corticosteroid binding was not decreased at 5 days after HCX. The relative increase in Bmax reached a maximum of 39% over control levels at 30 days postsurgery and recovery towards control values after longer survival did not occur. The increase in corticosteroid receptor capacity after HCX, therefore, is transient in the presence of adrenocortical secretion and permanent in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Obesity induced by kainic acid microlesion in the ventromedial hypothalamus in rats.

The neurotoxin kainic acid was injected bilaterally into the ventromedial hypothalamus of female rats in doses of 100 or 200 ng. The injections produced microlesions which led to progressive body weight gain and fat deposition in dose dependent manner. The histological examination revealed that the lesions were mainly located in the region between the ventromedial hypothalamic nuclei and the fornix.

Animals↗

Changes in avoidance behaviour following ethanol treatment in rats of different ages.

Avoidance learning and pain sensitivity were studied in rats after chronic ethanol administration (1.1 to 1.7 g per kg b.w. in drinking water) at prenatal, adolescent and adult ages. The behavioural reactions were tested in adulthood by studying passive and active avoidance learning and the threshold of pain sensitivity to electric tail shock. Chronic ethanol consumption led to an impairment of avoidance learning and to hyperalgesia in each experimental series, although the alterations were greater in the prenatally treated groups. The experimental observations are discussed in the light of fetal alcohol syndrome.

Alcoholism↗

Beneficial effect of chronic treatment with Org 2766 and alpha-MSH on impaired reversal learning of rats with bilateral lesions of the parafascicular area.

The effects of chronic treatment with the ACTH-(4-9) analogue Org 2766, alpha-MSH, and gamma 2-MSH were studied on T-maze reversal learning and on behavior assessed on the basis of open-field and other gross behavioral activities, grasping responses, inspection of various reflexes and electrical footshock sensitivity of rats with parafascicular lesions or sham-lesions. Repeated administration of Org 2766 and alpha-MSH to parafascicular area-lesioned rats resulted in functional recovery of impaired T-maze reversal learning. The structurally related neuropeptide gamma 2-MSH was without any effect. The alpha-MSH effect did not depend on time after lesioning as treatments during the first or second post-operative week were equally effective. Chronic peptide treatments did not change disturbed motor functions of parafascicular-lesioned rats, as measured by open-field activity, other gross behavioral activities and grasping responses. Since acute peptide treatments did not affect the impaired reversal learning performance of lesioned rats, the beneficial effect of Org 2766 and alpha-MSH could not be explained as a short-term effect on attention and motivation. It was more likely to be an accelerated recovery of cognitive function as a result of long-term neurotropic influences.

Adrenocorticotropic Hormone↗

Hippocampal kindling: corticosterone modulation of induced seizures.

The effect of adrenalectomy (ADX) and corticosterone replacement was studied on seizures induced by hippocampal kindling. A complex series of changes occurred in after-discharge (AD) and behavioural depression (BD) during the immediate hours after ADX, culminating at day 1 in markedly decreased AD and BD, which returned to normal over the next several days. These changes were normalized after replacement of the ADX group with low doses of corticosterone. It is concluded that the expression and maintenance of hippocampal kindled seizures is under short-term control of corticosterone.

Adrenalectomy↗