Bilateral Adrenalectomy: Effect on Cognitive Behavior and Neurodegeneration

Abstract

Event Abstract Back to Event Bilateral Adrenalectomy: Effect on Cognitive Behavior and Neurodegeneration Abdu Adem1*, Mohamed A. Fahim2 and Mohamed Y. Hasan1 1 United Arab Emirates University, Department of Pharmacology, United Arab Emirates 2 Emirates College for Advanced Education, Abu Dhabi, P.O Box, 126662, Abu Dhabi, UAE, Division of Health and Special Education,, United Arab Emirates The hippocampus, a brain region involved in learning and memory, is thought to play an important role in the functions of the hypothalamic-pituitary-adrenal axis1 . It is well established that the hippocampus has an important role in memory function2. The dentate gyrus, CA1 and CA3 regions of the hippocampus appear to be critically involved in cognitive function. In aged rats, loss of synapses in the dentate gyrus was related to memory deficits3 , as is loss of neurons in the CA1 and CA3 regions4 . In younger animals, colchicine and kainic acid-induced lesions of granule cells and CA3-CA4 regions respectively impair formation of place learning5 . All the above data indicate the importance of hippocampus in memory. The hippocampus is critically involved in mediating spatial learning6 (Morris et al., 1982). METHODS We investigated the effects of long-term adrenalectomy, 5 months after surgery, on spatial memory tasks. Moreover, the effect on locomotion and rearing were also investigated. The fact that adrenalectomy produces impairment of spatial learning led us to determine the loss of hippocampal neurons. In this respect we investigated the effect of long-term adrenalectomy on hippocampal neuronal survival. The neuroendocrine and the immune systems are interconnected. Monoclonal antibodies against major histocompatibility complex (MHC) class I, class II, CD4, CD8, pan T cells, and macrophages were used for immunostaining brains from adrenalectomized (ADX) and sham operated rats to investigate the potential involvement of the immune/inflammatory mechanisms in the neurodegeneration of hippocampus after ADX. Using various antibodies to the amyloid ß precursor protein (APP) associated with Alzheimer’s disease, we investigated changes in the distribution of APP in the hippocampus and neocortex of adrenalectomized (ADX) rats. RESULTS Our results showed that the performance of bilateral adrenalectomised rats in the Morris water maze was significantly retarded when compared to sham-operated rats7 . Oitzl and De Kloet [1992] found that adrenalectomy impaired performance of rats in the maze 3 days after the surgery8. Conrad and Roy [1993] attributed the learning deficits in long-term adrenalectomised rats to the dentate gyrus damage, rather than to absence of corticosterone, since the adrenalectomised rats were still impaired even when corticosteroids were administered exogenously during training9. In the retention test, in contrast to the observations of Conrad and Roy [1993]9 we observed that the ADX rats spent significantly shorter time in the platform circle compared to the sham and the naive controls7. This further strengthens our finding that the ADX rats were more significantly impaired in learning the Morris water maze task compared to the sham and the naive control rats. Our findings of the open-field test showed no differences in number of locomotion counts between ADX and sham-operated rats. However, rearing was significantly decreased in the ADX compared to the sham and the naive control rats. Since rearing represents more explorative behavior, it can be suggested that rearing is probably more affected by adrenalectomy7. Our results showed that the complete absence of adrenocortical hormones after long-term adrenalectomy leads to granular as well as pyramidal neuron degeneration10 . Our results demonstrate upregulation of MHC class II, CD4 antigens and activated microglial marker-ED1 expression selectively in the hippocampus after ADX. The absence of CD5 reactivity precludes that these activated cells were T lymphocytes11. The activated microglial cells may either be instrumental in the hippocampal neuronal loss or activated secondarily to the neuronal degeneration after long-term adrenalectomy11. Our results showed that 5 months ADX rats showed striking APP reactivity in the CA1–CA4 fields and in the surviving cells in the dentate gyrus. These findings suggest the enhanced APP reactivity in hippocampal neurons after long-term hormone deprivation would be another factor, which may influence the expression of APP in brain12. CONCLUSIONS In conclusion, our findings demonstrate that long-term adrenalectomy results in impairment of spatial learning and a decrease of explorative behaviour in ADX rats7.