Introduction: Hormonal imbalances are involved in many related pathologies, such as neurodegenerative and psychiatric disorders. Adult hypothyroidism is a prevalent condition in humans with an incidence of 8% in the adult population and could impair learning and memory processes. Even though tetra-iodothyronine (T4) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. Donepezil (DON) was a cholinesterase inhibitor, that can effectively improve the cognitive and memory impairments.
Aim of work: This work analyzed the histological and biochemical changes in the hippocampal Cornu Ammonis (CA1) region occurring in experimental hypothyroidism and assessed the possible role of Donepezil in such condition.
Materials and Methods: Forty eight healthy adult male rats were randomly divided into four groups; Group I (control group), rats of group II were subjected to thyroidectomy, Group III (thyroid-supplemented) and Group IV (combined DON+thyroxin). The hippocampus (CA1 region) sections were prepared and stained with hematoxylin and eosin and Cresyl fast violet. Immunohistochemical staining for glial fibrillary acid protein (GFAP), P53 and calretinin and electron microscopic examination were also done. The results were statistically analyzed.
Results: Hippocampus of hypothyroid adult rats displayed increased apoptosis in neurons and astrocytes with reactive gliosis as compared with controls. Moreover, the oxidative stress markers increased. Thyroid replacement induced some improvement, however DON could improve some of alterations to be similar to normal.
Conclusion: Our data concluded that adult hypothyroidism affects the hippocampus by a mechanism that alters the composition of GFAP, reduced neuronal and astrocyte survival, and alters the content of oxidative redox. Thyroxin replacement improved the structural alterations within limits. However combined thyroxin with DON could improve almost all of the biochemical and histological alterations.