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W Mayo

Publications and source records attributed to W Mayo.

52 records · Page 3Linked to original sources
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↗
PubMed1989

Comparative study of two types of cholinergic lesion in rats.

The cholinergic systems of the forebrain may be divided in two major sub-units: the septohippocampal system and the innominate-cortical system. This analysis is limited to the behavioral effects of lesions of pathway origins i.e. Medial Septal Area (MSA) and Nucleus Basalis of Meynert (NBM). Working memory is regularly involved by MSA lesion; NBM lesions also seem to affect working memory but is more often the cause of altered reference memory. However, multiple techniques of lesions are used, impairing interpretation of all the results by their bias and discrepancies.

Animals↗
PubMed1988

Memory disturbances following ibotenic acid injections in the nucleus basalis magnocellularis of the rat.

The behavioral effects of lesions of the nucleus basalis magnocellularis (NBM) on two spatial discrimination tasks (place navigation and cross maze) were examined in the rat. These tasks were designed to test reference memory. Lesions by bilateral injection of ibotenic acid into the NBM led to a severe and permanent impairment in the learning of the cross maze task. In the learning of the place navigation task, the rats with lesions showed only a transient deficit. Immediately after the removal of the platform, the rats with lesions explored the quadrant (NE) previously containing the platform as long as controls and above chance levels. The rats with lesions did not extinguish exploration like the controls, seen as a reduction both in time spent in the NE quadrant and in swimming activity. Taken together, the results showed that (1) NBM lesions impair reference memory, but (2) spare other aspects of memory. On the basis of the results in the place navigation task, procedural memory was assumed to remain intact after lesion of the NBM. Biochemical assays of choline acetyltransferase (ChAT) in various brain regions in the lesioned animals demonstrated a reduced ChAT activity in the neocortical projections of the NBM but not in the hippocampus. However, it cannot be decided from this work whether behavioral deficits result from the lesion of cholinergic or of non-cholinergic cells in the NBM.

Animals↗
PubMed1988

Locomotor hyperactivity in the rat after infusion of muscimol and [D-Ala2]Met-enkephalin into the nucleus basalis magnocellularis. Possible interaction with cortical cholinergic projections.

Locomotor activity in the rat was studied after infusion of GABAergic and enkephalinergic agonists into the nucleus basalis magnocellularis (NBM) of the forebrain. The experiments were designed to find out whether pharmacological blockade of cholinergic neurons in the NBM had similar behavioral effects to those observed after lesion of the same structure. Three experiments were carried out. In the first experiment, infusion of the GABAergic agonist muscimol (50 ng) into the NBM led to a marked locomotor hyperactivity. In the second experiment, it was shown that muscimol-induced locomotor response was reduced by pretreatment with the GABAergic antagonist picrotoxin (3 mg/kg). Further, locomotor hyperactivity was also observed after injection of the indirect GABA agonist, ethanolamine-o-sulfate (50 micrograms) into the NBM. The third experiment was designed to investigate the relationship between the blockade of NBM cholinergic neurons and the development of locomotor hyperactivity. The locomotor hyperactivity produced by the cholinergic antagonist scopolamine (0.4 mg/kg) was increased two-fold after infusion of 10 ng muscimol into the NBM. This dose of muscimol on its own had no effect on locomotor behavior. Similar enhancement of the locomotor response to that found with GABAergic agonists was observed after infusion of [D-Ala2]Met-enkephalinamide (2.5 micrograms) into the NBM. This enkephalin mediated locomotor response was blocked by the opiate antagonist naloxone (2 mg/kg). Pharmacological manipulations of the afferent inputs to the NBM could therefore be of value in studies on the behavioral role of cholinergic neurons in the NBM.

Animals↗
PubMed1987

Intraoperative cyanosis: a case of dapsone-induced methaemoglobinaemia.

Intraoperative cyanosis is most commonly caused by hypoxaemia. The anaesthetist is required to perform a rapid series of diagnostic manoeuvres and take remedial action. Occasionally methaemoglobin, sulfhaemoglobin, or haemoglobin M, undetected preoperatively, is the cause of the cyanosis. We report a case of methaemoglobinaemia secondary to dapsone ingestion that was diagnosed intraoperatively. Dapsone, a sulfone, is used therapeutically to treat leprosy and dermatitis herpetiformis. The differential diagnosis of cyanosis, and the origin and fate of methaemoglobin are discussed. In addition the diagnostic steps and the laboratory investigations required to make the diagnosis are listed.

Adolescent↗
PubMed1985

Profound disturbances of spontaneous and learned behaviors following lesions of the nucleus basalis magnocellularis in the rat.

It has been shown that a marked decline in the cortical activity of the cholinergic synthesizing enzyme choline-acetyltransferase (ChAT), accompanied by a severe neuronal loss in the nucleus basalis magnocellularis of Meynert occurs in the brains of patients with senile dementia of the Alzheimer type. However, the functional role of these neurons is largely unknown. In fact, very few studies have been done in animals. In this paper we report the behavioral effects of the lesion of the nucleus basalis magnocellularis in the rat either by radiofrequency current or by ibotenic acid injection at the level of the cell bodies. The two kinds of lesion lead to a profound disturbance of spontaneous and learned behaviors. There is a complete disorganization of behavior which is evidenced by an enhanced locomotor activity, an alteration in alimentary and hoarding behavior. In addition, we observed a deterioration of spatial memory and an incapacity to reverse a previously learned response. Biochemical assay showed that radiofrequency and ibotenic acid lesions produced a decrease of ChAT activity in the prefrontal and sensorimotor cortices and in amygdala without affecting the hippocampus or striatum. Ibotenic acid lesions seem to specifically destroy the cell bodies of the nucleus basalis magnocellularis since the dopaminergic and noradrenergic fibers of passage remained intact as measured by the unchanged level of endogenous catecholamine concentration in the terminal region in the prefrontal cortex. Presently, it cannot be said that the behavioral syndrome results solely from the lesion of the cholinergic neurons. Also, it is likely that the lesion of the nucleus basalis magnocellularis in the rat does not exactly reproduce the behavioral syndrome observed in Alzheimer's disease in man. However, this experimental approach in leading to a better knowledge of the functioning of these neurones could improve our understanding of this disease.

Animals↗
PubMed1984

Cortical cholinergic projections from the basal forebrain of the rat, with special reference to the prefrontal cortex innervation.

The topographic organization of cells containing choline-acetyltransferase (CAT) and located within the magnocellular nuclei of the basal forebrain was studied by correlating maximum CAT decrease in one or another cortical region with a given localization of the cell lesions. Lesions were made by using ibotenic acid. Lesions affecting the ventral pallidum decreased CAT activity in the antero-medial prefrontal cortex and lesions of the internal and ventral borders of the pallidum decreased CAT activity in sensori-motor and parieto-temporal cortices. None of these lesions produced a decrease of CAT activity in the hippocampus. These results suggest that it is possible to show the presence of a specific cholinergic projection from the basal forebrain to the medial-associative prefrontal cortex of the rat.

Animals↗
PubMedDate not supplied

New insights into the role of neuroactive steroids in cognitive aging.

The aim of this article is to describe neuroactive steroid research that has been focused on their physiological role in cognitive aging, an attractive new field in experimental gerontology. Neuroactive steroids have been recently proposed as biomarkers of cognitive aging, however, their specific functions have not yet been fully established. For instance, data emerging from human and animal studies suggest a complex relationship between neuroactive steroids and/or metabolites and cognitive processes during aging. Thus, a better knowledge of neuroactive steroid brain distribution and function could broaden our understanding of their physiological roles and lead to novel and more effective treatments for the management of age-related brain disorders. To this end, newly developed sensitive, specific, and accurate mass spectrometry assays may allow the quantification of neuroactive steroids in discrete brain regions and greatly contribute to unravel their role in age-related cognitive deficits.

Aged↗
PubMedDate not supplied

Effect of aging on the basal expression of c-Fos, c-Jun, and Egr-1 proteins in the hippocampus.

In the present study the effect of aging on the basal expression of three different immediate early genes (IEGs) was investigated. The protein products of c-fos, c-jun, and egr-1 genes were visualized immunohistochemically in the rat hippocampus of young adult (4-month-old) and old rats (20-month-old). Astrocytes were quantified by GFAp immunostaining to determine whether changes in the expression of IEGs were correlated with modifications in this marker of degenerative changes. In the young adult rat brain, basal levels of c-Jun and Egr-1 but not c-Fos were detected within the hippocampal formation. Whereas very high basal levels of c-Jun were found in the dentate granule cells and in the pyramidal cells of the ventral hippocampus, Egr-1 was highly expressed in the CA1 pyramidal cells of the dorsal hippocampus. Aging was accompanied by a decrease in Egr-1 expression, by a decrease in total cell density, as well as by a loss of astrocytes in CA1 subfields. In contrast, basal expression of c-Fos and c-Jun as well as astrocyte density within the dentate gyrus were not affected by aging. No difference in these markers was observed in aged rats with or without impairment in spatial learning in a water maze. It was concluded that although these changes may reflect senescence-induced decline of brain function, they do not constitute the defect underlying the age-associated reduction in mnesic capability.

Aging↗
PubMedDate not supplied

PSA-NCAM: an important regulator of hippocampal plasticity.

The Neural Cell Adhesion Molecule (NCAM) serves as a temporally and spatially regulated modulator of a variety of cell-cell interactions. This review summarizes recent results of studies aimed at understanding its regulation of expression and biological function, thereby focussing on its polysialylated isoforms (PSA-NCAM). The detailed analysis of the expression of PSA and NCAM in the hippocampal mossy fiber system and the morphological consequences of PSA-NCAM deficiency in mice support the notion that the levels of expression of NCAM are important not only for the regulation and maintenance of structural changes, such as migration, axonal growth and fasciculation, but also for activity-induced plasticity. There is evidence that PSA-NCAM can specifically contribute to a presynaptic form of plasticity, namely long-term potentiation at hippocampal mossy fiber synapses. This is consistent with previous observations that NCAM-deficient mice show deficits in spatial learning and exploratory behavior. Furthermore, our data points to an important role of the hypothalamic-pituitary-adrenal axis, which is the principle adaptive response of the organism to environmental challenges, in the control of PSA-NCAM expression in the hippocampal formation. In particular, we evidence an inhibitory influence of corticosterone on PSA-NCAM expression.

Animals↗