Search PubMed⌕ Search

Biomedical subjects

M Gallagher

Publications and source records attributed to M Gallagher.

226 records · Page 13Linked to original sources
PubMedDate not supplied

Effects of age on pilocarpine-induced c-fos expression in rat hippocampus and cortex.

The effect of age on pilocarpine-induced expression of the immediate-early gene c-fos was examined in the hippocampus and cortex of Long-Evans rats. Rats were treated with either pilocarpine (25 mg/kg) or saline, and sacrificed 90 min. following injection. The level of c-fos mRNA and Fos-like protein expression was determined using in situ hybridization histochemistry, and immunocytochemistry, respectively. In saline-treated animals, comparable levels of c-fos mRNA and Fos-like protein were observed in the hippocampus and cortical regions of young (6 month) and aged (24-26 months) rats. The expression of Fos-like protein following pilocarpine treatment was increased, however, in frontal, retrosplenial, and cingulate cortex of aged compared to young rats. In frontal and retrosplenial cortex, the changes in Fos-like protein were accompanied by changes in c-fos mRNA expression. In contrast, no age difference was detected in the hippocampus or parietal cortex of pilocarpine-treated rats. These regionally-specific age differences in response to pilocarpine administration suggest that mechanisms localized to those areas play an important role in determining the response to cholinergic stimulation mediated through post-synaptic muscarinic receptors.

Aging↗
PubMedDate not supplied

Septo-hippocampal cholinergic and neurotrophin markers in age-induced cognitive decline.

Messenger RNA (mRNA) molecules encoding proteins related to the presynaptic cholinergic and neurotrophin systems were quantitated in the hippocampus and basal forebrain of Long-Evans rats with spatial learning ability assessed in the Morris water maze. The reverse transcriptase-polymerase chain reaction showed that the mRNAs for the low-affinity neurotrophin receptor (p75-NTR) and the growth-associated protein GAP-43 were decreased in level in the basal forebrain of aged-impaired rats. In the hippocampus of these aged-impaired rats, the mRNA for VGF, another neurotrophin-inducible gene, also was decreased. In situ hybridization histochemistry revealed that mRNAs for nerve growth factor (NGF) and brain-derived neurotrophic factor increased in level in the aged rat hippocampus; when age effects were removed, NGF mRNA level remained significantly correlated with maze performance. Enzyme-linked immunosorbent assay indicated that NGF protein was expressed at normal levels in the aged rat hippocampus. These mRNA and protein alterations may signify that a defect in neurotrophin signaling exists in the brains of aged Long-Evans rats, underlying reduced plasticity responses in the basal forebrain cholinergic system.

Aging↗
PubMedDate not supplied

No loss of synaptic proteins in the hippocampus of aged, behaviorally impaired rats.

The levels of three different synaptic proteins in the hippocampus of young (6 months of age) and aged (26-27 months of age) Long Evans rats were examined using quantitative Western blotting. An important feature to this study is that prior to the neurobiological analysis, hippocampal function was determined by assessing spatial learning ability in the Morris water maze. A subset of the aged rats was impaired on the learning task while the remaining aged cohort performed within the range of young rats. The amount of immunoreactivity for synaptophysin, synaptotagmin, and synaptosomal associated protein-25 did not differ between the young and aged rats. In addition, the aged rats with severe cognitive impairment had levels of these synaptic proteins that were similar to those of the aged rats with preserved cognitive function. This finding of no change in the levels of synaptic proteins suggests that substantial synapse loss in the hippocampal formation does not underlie cognitive decline in normal aging.

Aging↗
PubMedDate not supplied

Cognitive decline associated with normal aging in rats: a neuropsychological approach.

The effects of aging on cognitive capacities were examined by comparing the performance of young and old rats on tasks characterized as dependent on different brain systems. This neuropsychological approach was employed to determine the extent to which multiple neural systems are compromised in aging and whether deterioration of one system correlates with that of another. The two tasks used in the present study were an odor-guided recognition memory task, for which different aspects of performance have been shown to be dependent on the integrity of the orbital prefrontal and perirhinal-entorhinal cortex, and the Morris water maze, for which performance depends on the medial prefrontal cortex and hippocampus. Rats were trained on the recognition memory task under minimal memory load and then challenged with longer memory delays and higher levels of inter-item interference. Considerable variation was observed in the performance of aged rats on acquisition of the recognition memory task, and unlike young rats, some aged rats could not acquire the task. Nevertheless, those aged rats who did acquire the cDNM task performed as well as young animals when the memory delay was extended and interference was elevated. In addition, consistent with previous findings, the performance of the same aged rats was highly variable in the Morris water maze task. Furthermore, although correlations between scores on the two tasks for individual aged rats were not reliable, only those aged rats that performed outside the performance range of young rats in the water maze were impaired on acquisition of the recognition memory task. This pattern of findings is consistent with age-related dysfunction in multiple subdivisions of the prefrontal cortex as well as the hippocampus and suggests that these brain regions may deteriorate in the same subgroup of aged rats.

Aging↗
PubMedDate not supplied

Trimethyltin impairs retention of a passive avoidance task.

Trimethyltin is a neurotoxic organometal which produces neuronal damage in several limbic regions including the hippocampus, amygdala and the pyriform cortex. One administration of trimethyltin (5, 6 or 7 mg/kg) twenty one days prior to passive avoidance conditioning produced an impairment of retention when animals were tested 24 hours after training. Rats treated with trimethyltin exhibited shorter step-through latencies and freezing durations during the retention test. It was observed that the three dosages of trimethyltin were equally effective in disrupting retention performance. There retention deficits were not secondary to alterations in footshock sensitivity. The data presented here indicate that acute trimethyltin administration disrupted learning and memory. The compound might be a useful tool for examining the role of the limbic system in associative processes.

Analysis of Variance↗