Biomedical subjects

J L Bizon

Publications and source records attributed to J L Bizon.

8 recordsLinked to original sources

PubMed2004

Neurogenesis in a rat model of age-related cognitive decline.

Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.

Aging↗

PubMed2003

Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze.

Recent evidence has suggested that the relative levels of acetylcholine (ACh) between brain structures may be an important factor in the choice of behavioral strategy in settings in which either hippocampal or dorsal striatal brain systems can be employed both effectively and independently (McIntyre and Gold. 1999. Soc Neurosci Abs 25:1388). The current investigation used the neurotoxin 192 IgG-saporin to deplete the hippocampus of ACh selectively, while leaving ACh in other brain regions, including dorsal striatum, intact. Rats were then trained on a version of the Morris water maze, in which behavioral strategies attributed to the hippocampus and dorsal striatum are placed in direct competition. It was predicted that rats with hippocampal ACh depletion would display a cue bias. Contrary to this prediction, depleting hippocampal ACh did not bias against and, in fact, promoted use of a hippocampal place strategy in this task, as indicated by choice in competition tests and performance on hidden platform training trials. These data add to a growing literature demonstrating that the septohippocampal cholinergic system is not required for accurate spatial learning and suggest a complex role for basal forebrain projections in processing information about the spatial environment.

Acetylcholine↗

PubMed2003

Production of new cells in the rat dentate gyrus over the lifespan: relation to cognitive decline.

The identification of neurogenesis in the dentate gyrus of adult mammals has sparked much interest in a functional role for these new neurons in hippocampal-dependent cognition. The current investigation used a model of age-related cognitive decline in rodents to study the relationship between changes in markers of neurogenesis and hippocampal function. New cell production in the granule cell layer was progressively reduced across the lifespan of male Long Evans rats, with a 40% reduction at middle age (13 months) and a reduction in excess of 80% in advanced age (25 months), compared with young mature adults (7 months). These effects of aging were not, however, predictive of cognitive status. In particular, the pronounced decrease in new cell production during aging did not distinguish among rats that varied over a wide range of cognitive abilities.

Aging↗

PubMed2001

Hypothalamic-pituitary-adrenal axis function and corticosterone receptor expression in behaviourally characterized young and aged Long-Evans rats.

In the current investigation, hypothalamic-pituitary-adrenal (HPA) axis function was examined in young and aged male Long-Evans rats that were initially assessed on a version of the Morris water maze sensitive to cognitive impairment during ageing. In behaviourally characterized rats, a 1-h restraint stress paradigm revealed that plasma corticosterone concentrations in aged cognitively impaired rats took significantly longer to return to baseline following the stressor than did those in young or aged cognitively unimpaired rats. No differences in basal or peak plasma corticosterone concentrations, however, were observed between young or aged rats, irrespective of cognitive status. Using ribonuclease protection assays and in situ hybridization, we evaluated mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA abundance in young and aged rats characterized on the spatial task. Abundance of MR mRNA was decreased as a function of age in stratum granulosum but not hippocampus proper, and the decrease in MR mRNA was largely unrelated to cognitive status. However, GR mRNA was significantly reduced in several hippocampal subfields (i.e. stratum granulosum and temporal hippocampus proper) and other related cortical structures (medial prefrontal and olfactory regions) of aged cognitively impaired rats compared to either young or aged cognitively unimpaired cohorts, and was significantly correlated with spatial learning ability among the aged rats in each of these brain regions. In agreement with previous stereological data from this ageing model, no changes were detected in neuron density in the hippocampus of the rats used in the in situ hybridization analysis. These data are the first to describe a coordinated decrease in GR mRNA in a functional brain system including hippocampus and related cortical areas that occurs in tandem with impairments of the HPA response to stress and cognitive decline in ageing.

Adrenal Cortex Hormones↗

PubMed1999

Subpopulations of striatal interneurons can be distinguished on the basis of neurotrophic factor expression.

Substantial evidence supports a role for trophic activities in the function and survival of fully mature striatal neurons, but little is known regarding trophic factor expression in adult striatum. In situ hybridization was used to identify the distribution and the neurotransmitter phenotypes (i.e., cholinergic and gamma-aminobutyric acid [GABA]-ergic) of cells expressing acidic fibroblast growth factor (aFGF), glial cell line-derived neurotrophic factor (GDNF), or nerve growth factor (NGF) mRNA in adult rat striatum. Each trophic factor mRNA was localized to large, sparsely scattered striatal cells that corresponded to interneurons. Double-labeling studies demonstrated that NGF mRNA was expressed by GABAergic and never by cholinergic cells, whereas aFGF and GDNF mRNAs were expressed by both cell types. Approximately 75% of aFGF+ and GDNF+ cells in dorsal striatum and 46% of aFGF+ and 61% of GDNF+ cells in ventral striatum were cholinergic. Conversely, about 32% of aFGF+ and 24% of GDNF+ cells in dorsal striatum and 55% of aFGF+ and 27% of GDNF+ cells in ventral striatum were GABAergic. A portion of aFGF+ and NGF+ cells was of the parvalbumin GABAergic subtype. The colocalization of trophic factor expression was also examined. Of aFGF+ cells, 20% and 41% were NGF+ and 67% and 83% were GDNF+ in dorsal and ventral striata, respectively. These findings demonstrate that aFGF, GDNF, and NGF are synthesized by discrete but overlapping populations of striatal interneurons. The expression of these survival factors may contribute to the resistance of striatal interneurons to various insults including excitotoxicity.

Animals↗

PubMed1996

Acidic fibroblast growth factor mRNA is expressed by basal forebrain and striatal cholinergic neurons.

Evidence for the importance of the basal forebrain cholinergic system in the maintenance of cognitive function has stimulated efforts to identify trophic mechanisms that protect this cell population from atrophy and dysfunction associated with aging and disease. Acidic fibroblast growth factor (aFGF) has been reported to support cholinergic neuronal survival and has been localized in basal forebrain with the use of immunohistochemical techniques. Although these data indicate that aFGF is present in regions containing cholinergic cell bodies, the actual site of synthesis of this factor has yet to be determined. In the present study, in situ hybridization techniques were used to evaluate the distribution and possible colocalization of mRNAs for aFGF and the cholinergic neuron marker choline acetyltransferase (ChAT) in basal forebrain and striatum. In single-labeling preparations, aFGF mRNA-containing neurons were found to be codistributed with ChAT mRNA+ cells throughout all fields of basal forebrain, including the medial septum/diagonal band complex and striatum. By using a double-labeling (colormetric and isotopic) technique, high levels of colocalization (over 85%) of aFGF and ChAT mRNAs were observed in the medial septum, the diagonal bands of Broca, the magnocellular preoptic area, and the nucleus basalis of Meynert. The degree of colocalization was lower in the striatum, with 64% of the cholinergic cells in the caudate and 33% in the ventral striatum and olfactory tubercle labeled by the aFGF cRNA. These data demonstrate substantial regionally specific patterns of colocalization and support the hypothesis that, via an autocrine mechanism, aFGF provides local trophic support for cholinergic neurons in the basal forebrain and the striatum.

Animals↗

PubMed1996

In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long-Evans rats: relationship to spatial learning.

Using in vitro autoradiography, we investigated [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [3H]kainate and [3H]N-methyl-D-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been tested for spatial learning ability in the Morris water maze. Although there was substantial preservation of binding in the aged rats, reductions in binding were present in the aged rats that were specific to ligand and anatomical region. In the hippocampus of aged rats, [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [3H]kainate binding in CA3 were reduced. In contrast, N-methyl-D-aspartate binding was not significantly different between age groups. There was evidence of sprouting in the dentate gyrus molecular layer of aged rats, indicated by changes in the topography of [3H]kainate binding. Binding density was analysed with respect to patch/matrix compartmentalization in the striatum. The most striking result was a large decrease in N-methyl-D-aspartate binding in aged rats that was not limited to any dorsal/ventral or patch/matrix area of the striatum. Additionally, [3H]kainate binding in striatal matrix was modestly reduced in aged rats. Of these age effects, only N-methyl-D-aspartate binding in the striatum and [3H]kainate binding in the CA3 region of the hippocampus were correlated with spatial learning, with lower binding in the aged rats associated with better spatial learning ability. Age-related alterations in ionotropic glutamate receptors differ with respect to the receptor subtype and anatomical region examined. The age effects were not necessarily indicative of cognitive decline, as only two age-related binding changes were correlated with spatial learning. Interestingly, in these instances, lower binding in the aged rats was associated with preserved spatial learning, suggesting a compensatory reduction in receptor binding in a subpopulation of aged rats.

Aging↗

PubMed1995

NGF mRNA is expressed by GABAergic but not cholinergic neurons in rat basal forebrain.

Nerve growth factor (NGF) supports the survival and biosynthetic activities of basal forebrain cholinergic neurons and is expressed by neurons within lateral aspects of this system including the horizontal limb of the diagonal bands and magnocellular preoptic areas. In the present study, colormetric and isotopic in situ hybridization techniques were combined to identify the neurotransmitter phenotype of the NGF-producing cells in these two areas. Adult rat forebrain tissue was processed for the colocalization of mRNA for NGF with mRNA for either choline acetyltransferase, a cholinergic cell marker, or glutamic acid decarboxylase, a GABAergic cell marker. In both regions, many neurons were single-labeled for choline acetyltransferase mRNA, but cells containing both choline acetyltransferase and NGF mRNA were not detected. In these fields, virtually all NGF mRNA-positive neurons contained glutamic acid decarboxylase mRNA. The double-labeled cells comprised a subpopulation of GABAergic neurons; numerous cells labeled with glutamic acid decarboxylase cRNA alone were codistributed with the double-labeled neurons. These data demonstrate that in basal forebrain GABAergic neurons are the principal source of locally produced NGF.

Acetylcholine↗