Learning Memory Function Research Articles

The canine as an animal model of human aging and dementia

The aged canine displays many features that make it an excellent model for studying the progression of pathology in brain aging and linking these findings to learning memory and other cognitive functions. Canines develop extensive β-amyloid deposition within neurons and their synaptic fields which appears to give rise to senile plaques. These plaques are primarily of the early diffuse subtype. Aged canines also exhibit accumulations of lipofuscin cerebral vascular changes, dilation of the ventricles and cytoskeletal changes. Neurofibrillary tangles (NFT s) are not present in the aged canine. Thus, the aged canine brain provides a suitable model for studying early degeneration normally considered to be pre-Alzheimer's. This supposition is also supported by behavioral data. We have found that the extent of β-amyloid deposition correlates with a decline in select measures of cognitive function. These data provide the first evidence of a correlation between β-amyloid accumulation and cognitive decline in the absence of NFTs. We summarize four lines of evidence that support using the aged canine as a model of human aging: (a) Aged canines develop aspects of neuropathology similar to that observed in aged humans; (b) Veterinarians have observed that many canines exhibit a clinical syndrome of age-related cognitive dysfunction; (c) Aged canines are deficient on a variety of neuropsychological tests of cognitive function; (d) The level of β-amyloid accumulation correlates with cognitive dysfunction in the canine. These data indicate that the aged canine is a particularly useful model for studying age-related cognitive dysfunction (ARCD), early neuronal changes associated with aging, and the initial stages of senile plaque formation.

Choline acetyltransferase, nerve growth factor and cytokine levels are changed in congenitally hydrocephalic HTX rats.

The forebrain cholinergic system is correlated with learning ability and memory function. Here changes in choline acetyltransferase (ChAT) activities, nerve growth factor (NGF) concentrations and expression of IL-1 beta and IL-6 genes were determined in the basal forebrain, parieto-occipital cortex and hippocampus of hydrocephalic and nonhydrocephalic HTX rats. ChAT activity was remarkably decreased in the parieto-occipital cortex of hydrocephalic animals compared to the other two regions. On the other hand, the NGF concentration in the parieto-occipital cortex was markedly increased during the progression of hydrocephalus compared to the basal forebrain and hippocampus. IL-1 beta and IL-6 m-RNA were detectable only in hydrocephalic HTX rats. The disturbance of uptake and transport of NGF in the affected cerebral cortex is partly related to the psychomotor maldevelopment of congenital hydrocephalic children.

Effect of Clonazepam on Brain Development of Mice

Twenty-seven Kun-Ming white mice were divided randomly into three groups of 9 animals. One of these groups served as a control group. Clonazepam (CZP), 0.1 or 0.5 mg/kg/day, was administered by oral gavage for 22 days. The water-maze test was performed before giving CZP and 10 and 22 days later. The step-down test was performed on the 1st and the 2nd day after discontinuing CZP treatment to determine toxic effects on brain development and learning-memory function. Body weights and brain weight were also recorded. Brain development and learning-memory function, evaluated by water-maze and step-down tests, were not impaired by CZP. Although there was a trend toward lower weights in the higher-dose group, CZP treatment did not significantly affect either body weight or total or regional brain weight. The results of this study indicate that 4 weeks of treatment with CZP does not impair brain development and learning-memory function in baby mice.