Biomedical subjects

W Mayo

Publications and source records attributed to W Mayo.

At least 19 recordsLinked to original sources

PubMed1997

Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus.

Pregnenolone sulfate (PREG S) is synthesized in the nervous system and is a major neurosteroid in the rat brain. Its concentrations were measured in the hippocampus and other brain areas of single adult and aged (22-24 month-old) male Sprague-Dawley rats. Significantly lower levels were found in aged rats, although the values were widely scattered and reached, in about half the animals, the same range as those of young ones. The spatial memory performances of aged rats were investigated in two different spatial memory tasks, the Morris water maze and Y-maze. Performances in both tests were significantly correlated and, accompanied by appropriate controls, likely evaluated genuine memory function. Importantly, individual hippocampal PREG S and distance to reach the platform in the water maze were linked by a significant correlation, i.e., those rats with lower memory deficit had the highest PREG S levels, whereas no relationship was found with the PREG S content in other brain areas (amygdala, prefrontal cortex, parietal cortex, striatum). Moreover, the memory deficit of cognitively impaired aged rats was transiently corrected after either intraperitoneal or bilateral intrahippocampal injection of PREG S. PREG S is both a gamma-aminobutyric acid antagonist and a positive allosteric modulator at the N-methyl-D-aspartate receptor, and may reinforce neurotransmitter system(s) that decline with age. Indeed, intracerebroventricular injection of PREG S was shown to stimulate acetylcholine release in the adult rat hippocampus. In conclusion, it is proposed that the hippocampal content of PREG S plays a physiological role in preserving and/or enhancing cognitive abilities in old animals, possibly via an interaction with central cholinergic systems. Thus, neurosteroids should be further studied in the context of prevention and/or treatment of age-related memory disorders.

Aging↗

PubMed1997

Inter-individual differences in the effects of acute stress on the sleep-wakefulness cycle in the rat.

It has been described that an acute immobilization stress (IS) modifies subsequent paradoxical sleep (PS). However, its effects are complex because some subjects remain unaffected. This discrepancy might result from constitutive inter-individual psychobiological differences. In order to test this hypothesis, an inter-individual analysis of sleep patterns and their modifications after 60 min IS has been performed. Even though global analysis showed a PS increase after IS, inter-individual analysis evidenced different PS reactivity; subjects which had the least PS during control recordings were those with the largest PS increase. Unlike global analysis, an inter-individual study evidenced different modifications of wakefulness and slow wave sleep according to individuals. Subjects presenting the highest amount of wakefulness in control conditions (the lowest amount of slow wave sleep) decreased their wakefulness amount, while subjects with the lowest amount of wakefulness increased it. Thus, individual characteristics of the sleep-wakefulness cycle should be considered while studying its modifications induced by different treatments.

Animals↗

PubMed1997

Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion.

It is well known that the hypothalamo-pituitary-adrenal (HPA) axis is altered by early environmental experiences, particularly in the perinatal period. This may be one mechanism by which the environment changes the physiology of the animal such that individual differences in adult adaptative capabilities, such as behavioral reactivity and memory performance, are observable. To determine the origin of these behavioral individual differences, we have investigated whether the long-term influence of prenatal and postnatal experiences on emotional and cognitive behaviors in adult rats are correlated with changes in HPA activity. To this end, prenatal stress of rat dams during the last week of gestation and postnatal daily handling of rat pups during the first 3 weeks of life were used as two environmental manipulations. The behavioral reactivity of the adult offspring in response to novelty was evaluated using four different parameters: the number of visits to different arms in a Y-maze, the distance covered in an open field, the time spent in the corners of the open field, and the time spent in the open arms of an elevated plus-maze. Cognitive performance was assessed using a water maze and a two-trial memory test. Adult prenatally stressed rats showed high anxiety-like behavior, expressed as an escape behavior to novelty correlated with high secretion of corticosterone in response to stress, whereas adult handled rats exhibited low anxiety-like behavior, expressed as high exploratory behavior correlated with low secretion of corticosterone in response to stress. On the other hand, neither prenatal stress nor handling changed spatial learning or memory performance. Taken together, these results suggest that individual differences in adult emotional status may be governed by early environmental factors; however, perinatal experiences are not effective in influencing adult memory capacity.

Analysis of Variance↗

PubMed1997

Decrease in highly polysialylated neuronal cell adhesion molecules and in spatial learning during ageing are not correlated.

Age-dependent spatial memory impairments have been related to a decline in hippocampal plasticity. Highly polysialylated neuronal cell adhesion molecules (PSA-NCAM) show a strong expression during adulthood within regions associated with neuroplastic events. Furthermore, NCAM molecules have been proposed to mediate neuronal plasticity during learning and memory. The aim of the present study was to examine the effect of ageing on the expression of PSA-NCAM within the hippocampus. To investigate whether age-dependent changes in expression of PSA-NCAM were accentuated in aged rats with learning impairment, animals were in a first step assessed for their cognitive abilities using a Morris water maze. Seven-month-old and 24-month-old-rats were tested for their performance in the Morris water maze. The animals were sacrificed and brain sections were processed for PSA-NCAM immunohistochemistry. Ageing was accompanied by an overall decrease in PSA-NCAM-immunoreactivity (-IR) within the forebrain, presenting a important decrease of the number of PSA-NCAM-IR perikarya within the hippocampus. These results were confirmed by Western blot analysis. No difference in PSA-NCAM immunoreactivity was observed in aged rats with or without spatial learning impairment. It is concluded that although changes in PSA-NCAM accompanied the decrease in cognitive abilities, our data did not evidence a causal relationship between these two parameters.

Aging↗

PubMed1997

Facilitation of cognitive performance in aged rats by past experience depends on the type of information processing involved: a combined cross-sectional and longitudinal study.

The impact of past history on behavior across the life span is largely unknown. This is why the role of previous experience in subsequent memory performances has been studied in a combined longitudinal (animals repeatedly tested) and cross-sectional (animals tested once at various ages) study, in male Sprague-Dawley rats. Different types of memory (reference and working memory) and/or information processing (route or place learning) were assessed in three different tasks (T-maze, Morris water maze, and eight-arm radial maze). Our results indicate that experience prevents age-related impairments in the learning phase of the T-maze and the Morris water maze, in both middle-aged and old rats. Nonexperienced animals of the same age were found to present age-related memory deficits. However, previous experience did not have any effect on the learning of the radial maze or on the reversal performance. It is suggested that controlled processes (intentional and attentional) are impaired by aging and cannot be improved by training, whereas automated processes appear to benefit from it. These data underline the heterogeneity of cognitive aging and indicate that aging is not inevitably accompanied by a decline in performance.

Aging↗

PubMed1996

Early and later adoptions have different long-term effects on male rat offspring.

Both prenatal and postnatal environmental factors exert complex influences on the development of an organism. Previous studies have demonstrated that intervening events during the prenatal period can have different and even opposite effects than similar intervening events occurring in the postnatal period. We have reported previously that early postnatal adoption prevents prenatal stress-induced long-term impairments in glucocorticoid feedback. To characterize further the effects of adoptions during the postnatal period, adoptions have been performed at different times, and the effect on the postnatal ontogeny of the hypothalamo-pituitary-adrenal axis has been investigated. Adoptions were performed during the first hour after birth (A1) and on the fifth (A5) and twelfth (A12) days after birth. At each of these times, other litters (S1, S5, S12) underwent a "separation" controlling for the 1 min maternal separation necessary for the adoptions. Locomotor behavior, cognition, and stress-induced corticosterone secretion in the adult male offspring have been examined, along with maternal behavior. Early adoption (A1) was found to prevent the prolonged stress-induced secretion of corticosterone evident in early separated (S1) offspring. Similarly, A1 rats demonstrated lower novelty-induced locomotion and improved recognition performance in a Y-maze compared to S1 offspring. However, later adoption (A5, A12) prolonged stress-induced corticosterone secretion, increased the locomotor response to novelty, and disrupted cognitive performance in the offspring. Only the early adoption increased maternal licking behavior, a factor that may have a protective effect on the pups. Taken together, these results suggest that the same postnatal manipulation realized at different times can induce different, or even opposite, effects on the behavioral and neuroendocrine characteristics of the adult offspring.

Aging↗

PubMed1996

Long-term effects of prenatal stress and handling on metabolic parameters: relationship to corticosterone secretion response.

The prenatal and postnatal environment exerts a long-term influence on the stress-response of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the long-term effects of prenatal and postnatal manipulations and their related changes on glucocorticoid secretion were examined on metabolic parameters in adult rats. Plasma glucose levels, body weight and basal feeding behavior were measured. We show that modifications of the prenatal and postnatal environment have opposite long-term effects on these parameters, except for blood glucose, which was increased in prenatally stressed animals. Although the mechanisms underlying these phenomena remain to be elucidated, the observations show that perinatal manipulations have long-term effects on metabolic functions related to HPA activity.

Animals↗

PubMed1996

Behavioral reactivity to novelty during youth as a predictive factor of stress-induced corticosterone secretion in the elderly--a life-span study in rats.

Inter- and intra-individual differences in hypothalamo-pituitary adrenal (HPA) axis activity and behavioral reactivity to novelty between young and old rats were evidenced in this longitudinal life-span study. Higher responders to novelty (HR) had a higher corticosterone secretion which showed a quicker increase with age than did the others (LR); the differences in response to novelty observed in youth were no longer apparent in the old rats. Response to novelty in youth is a predictive factor of accelerated aging of the HPA axis. These early changes, which precede the appearance of the memory deficits, may be a causal factor. Disappearance of behavioral and endocrinological inter-individual differences at 21 months highlights the importance of not restricting aging studies to old subjects.

Aging↗

PubMed1996

Novelty-seeking in rats--biobehavioral characteristics and possible relationship with the sensation-seeking trait in man.

A behavioral trait in rats which resembles some of the features of high-sensation seekers in man has been characterized. Given that the response to novelty is the basis of the definition of sensation-seeking, individual differences in reactivity to novelty have been studied on behavioral and biological levels. Certain individuals labeled as high responders (HR) as opposed to low responders (LR) have been shown to be highly reactive when exposed to a novel environment. These groups were investigated for free-choice responses to novel environments differing in complexity and aversiveness, and to other kinds of reinforcement, i.e. food and a drug. The HR rats appeared to seek novelty, variety and emotional stimulation. Only HR individuals have been found to be predisposed to drug-taking: they develop amphetamine self-administration whereas LR individuals do not. They also exhibit a higher sensitivity to the reinforcing properties of food. On a biological level, compared to LR rats, HR animals have an enhanced level of dopaminergic activity in the nucleus accumbens both under basal conditions or following a tail-pinch stress. HR and LR rats differ in reactivity of the corticotropic axis: HR rats exposed to a novel environment have a prolonged secretion of corticosterone compared to LR rats. The association of novelty, drug and food seeking in the same individual suggests that these characteristics share common processes. Differences in dopaminergic activity between HR and LR rats are consistent with results implicating these dopaminergic neurons in response to novelty and in drug-taking behavior. Given that rats self-administer corticosterone and that HR rats are more sensitive to the reinforcing properties of corticosteroids, it could be speculated that HR rats seek novelty for the reinforcing action of corticosterone. These characteristics may be analogous to some for the features found in human high-sensation seekers and this animal model may be useful in determinating the biological basis of this human trait.

Animals↗

PubMed1995

Biosynthesis and assay of neurosteroids in rats and mice: functional correlates.

Pregnenolone (PREG), synthesized de novo in rodent brain, is the precursor of PREG sulfate (S) and progesterone (PROG). PROG is further converted to 5 alpha-pregnane 3, 20-dione (DH PROG) and to 3 alpha-hydroxy-5 alpha-pregnan-20-one (TH PROG). PROG, DH PROG and TH PROG have been measured in the brain of male and female rats. Neither PROG nor DH PROG disappeared from brain, contrary to plasma, after combined adrenalectomy (ADX) and gonadectomy (CX). Trilostane decreased PROG and increased PREG in the brain of CX+ADX rats and mice, in accordance with a precursor to product relationship. As previously described in CX male mice, the neurosteroid DHEA and its analog 3 beta-methyl-androst-5-en-17-one (CH3-DHEA) inhibited the aggressive behavior of female mice towards lactating female intruders. The decrease of biting attacks by DHEA was definitely more prominent in females neonatally imprinted with testosterone. The degree of inhibition of aggressive behavior was related to the decrease of PREG S concentrations in brain. The memory-enhancing effects of DHEA S and PREG S in male mice have been previously documented. Infusion of PREG S (12 fmol) into the nucleus basalis magnocellularis (NBM) of the rat after the acquisition trial enhanced memory performance in a two-trial recognition task (TTRT). Conversely, TH PROG (6 fmol), which potentiates GABAergic neurotransmission, disrupted performance when injected before the acquisition trial. Accordingly, we have found a positive correlation between the performances of 2-year-old rats in the TTRT and the concentrations of PREG S in the hippocampus, namely animals which performed best had the highest steroid levels.

Adrenalectomy↗

PubMed1994

Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly: a longitudinal study in rats.

A life-span study of certain behavioral traits was conducted in rats. Animals were repeatedly tested in a circular corridor for reactivity to novelty and in a recognition memory task for cognitive abilities. These measures revealed important inter-individual differences in young as well as in old subjects. Some of these differences appear with aging (memory deficits) and others disappear (high reactivity to novelty). Moreover, a relationship between high reactivity to novelty in youth and deficits in memory recognition in elderly was found. Rats that are high-responders to novelty had age-related memory impairments whereas the low-responder rats did not. While the biological mechanism linking these two behavioral traits remains to be demonstrated, this study shows that age-related impairments can be predicted by factors detectable early in life.

Aging↗

PubMed1993

Infusion of neurosteroids into the nucleus basalis magnocellularis affects cognitive processes in the rat.

The neurosteroids, pregnenolone sulfate (PREG-S) and tetrahydroprogesterone (TH-PROG), act on the GABAA receptor with antagonist or agonist-like properties, respectively. In this study the effect of the infusion of PREG-S and TH-PROG into the nucleus basalis magnocellularis (NBM) of the rat was examined in a two-trial memory task. The results show that PREG-S (5 ng in 0.5 microliter) enhances memory performance when injected after an acquisition trial; conversely TH-PROG (2 ng in 0.5 microliter) disrupts performance when injected before an acquisition trial. A role for neurosteroids in memory processes subserved by the nucleus basalis magnocellularis is of interest in view of the implication of this structure and these substances in neurodegenerative processes.

Animals↗

PubMed1992

Cognitive enhancing properties of beta-CCM infused into the nucleus basalis magnocellularis of the rat.

Peripheral administration of various benzodiazepine derivatives or beta-carbolines (inverse agonists at benzodiazepine receptors), has been shown to affect memory. In this study, the effect of local infusion of a beta-carboline-methyl beta carboline-3-carboxylate (beta-CCM) into the nucleus basalis magnocellularis (NBM) of rats was examined in a two-trial recognition task. The results show that beta-CMM (3 micrograms/0.5 microliter) enhances recognition performance when injected both before or immediately after the acquisition trial. These effects appear to be mediated by a benzodiazepine (BZD) receptor since they were blocked by pretreatment with Ro 15-1788, a BZD receptor antagonist. This study supports the involvement of the NBM in cognitive processes, and demonstrates that these processes can be influenced by alteration of GABAergic neurotransmission.

Animals↗

PubMed1992

A two-trial memory task with automated recording: study in young and aged rats.

A two-trial recognition task, based on place or object exploration in a Y-maze, was developed to study memory in adult and aged rats. This paradigm avoids the use of electric shocks or deprivation that may have non-specific influences on the responses, and the task does not require learning of a rule. A number of behavioral parameters in several animals could be recorded automatically. These behavioral parameters were found to be differently influenced both by the type of recognition (place vs. object) and by the inter-trial interval (recognition retention time). Impaired recognition was also detected in 18-months-old rats. This recognition task which combines simplicity, sensitivity and high specificity may thus be a useful adjunct to our current battery of memory tasks.

Aging↗

PubMed1991

Learning disturbances following excitotoxic lesion of cholinergic pedunculo-pontine nucleus in the rat.

Compared to brain anterior cholinergic systems such as the septo-hippocampal and nucleus basalis-cortical pathways, posterior cholinergic groups have received little attention with respect to their involvement in learning and memory. In this study, the effect of lesion of the cholinergic pedunculo-pontine cell bodies (PPN) by the excitotoxin quisqualic acid was investigated on spontaneous locomotor activity and learning in rats. Behavioral tasks designed to test both reference memory (cross maze and water maze) or working memory (radial maze) were used. PPN lesion had no effect on initial nor on nocturnal locomotor activity in a circular corridor. The lesion disrupted learning in the water and radial mazes, but was without influence on acquisition in the cross maze. The difference in results obtained in the two tasks designed to test reference memory (cross maze and water maze) indicated that the disturbance depended on task difficulty rather than on a particular memory component. It is suggested that the PPN is involved in the sustained attention required to perform correctly in water and radial mazes. The PPN cannot therefore be considered as a uniquely extrapyramidal structure. In addition to its descending outputs, the PPN has ascending connections to the neocortex, either directly or indirectly via the thalamus, and so pathological changes in this region may be partly responsible for the cognitive disorders of aging or those observed in various neurodegenerative conditions.

Animals↗

PubMed1990

The nucleus basalis is involved in brain modulation of the immune system in rats.

Male rats were subjected to bilateral or unilateral excitotoxic lesions of the nucleus basalis magnocellularis (NBM). Three weeks after surgery, mitogen-induced lymphoproliferation and natural killer (NK) cell activity were determined in the spleen. T-cell mitogenesis and NK cell activity were strongly enhanced after bilateral lesions but were not affected after right or left unilateral lesions. B-cell mitogenesis and blood T-cell subset distribution remained unchanged after bilateral or unilateral lesions of the NBM. These results demonstrate that NBM cells are involved in the complex interrelations existing between the central nervous system and the immune system.

Animals↗

PubMed1990

Iodobenzamide for in vivo exploration of central dopamine receptors: evaluation in animal models of supersensitivity.

Iodobenzamide is a promising agent to investigate D2 receptors by SPECT in living human brain. In this work, we have evaluated this radiolabeled compound in two animal models of D2 receptors supersensitivity. In the first model, rats were treated chronically with haloperidol during three weeks (S.C. injection of 0.5 mg/kg/day). One week after the last day of treatment, they were I.V. injected with 125I-IBZM. In vivo specific binding study showed a 45 percent increase of 125I-IBZM fixation in the striatum of treated rats. In a second step of experiments, animals were unilaterally lesioned by a stereotaxic injection of 6-OHDA in the substantia nigra, 23 days before receiving 125I-IBZM. Autoradiographic analysis of coronal brain sections showed a 38 percent enhancement of 125I-IBZM in vivo binding in the striatum on the lesioned side as compared to the contralateral intact side; this increase occurred in striatal lateral area. These data demonstrate that 125I-IBZM is convenient to detect alterations of dopamine D2 receptors in vivo in the rat. Thus IBZM labelled with 123I can be a very useful imaging agent for the exploration of D2 receptors in pathological situations.

Animals↗

PubMed1990

Choline acetyltransferase activity and [3H]vesamicol binding in the temporal cortex of patients with Alzheimer's disease, Parkinson's disease, and rats with basal forebrain lesions.

[3H]Vesamicol binding was characterized in human brain post mortem. The number of binding sites was then determined in parallel with choline acetyltransferase activity in the temporal cortex of patients with Alzheimer's disease, demented and non-demented patients with Parkinson's disease, and in the cerebral cortex of rats with quisqualic acid lesions of the nucleus basalis magnocellularis. Whereas choline acetyltransferase activity decreased in patients with Alzheimer's or Parkinson's disease indicating loss of cholinergic innervation, the number of binding sites for [3H]vesamicol was the same as or higher than in controls. Similar results were obtained with the lesioned rats. It is suggested that the increase in binding sites may reflect compensatory regulation of the spared neurons at the level of the synaptic vesicle.

Aged↗