Cerebellum seems to be a specific target for both the decrease of estrogen and hypertension in menopause. The aim of this study was to investigate the hypertension and menopause-induced changes in rat's cerebellar cortex and the possible mechanisms of these changes. Rats were divided into four groups: the sham-operated control (SC-group), the ovariectomized (OVX-group), the hypertensive (H-group), and the ovariectomized-hypertensive (OVX-H-group) group. The mean arterial pressure (MAP), serum nitric oxide (NO), lipid peroxides and antioxidant catalase enzyme levels were assayed. Cerebellar tissue homogenization for analysis of lipid peroxides, antioxidant catalase enzyme, tumor necrosis factor-α (TNF-α), and estradiol was done. Quantification of adrenomedullin (AM) and interleukin-10 (IL-10) mRNA was also done. Cerebella were processed for histological, immunohistochemical and transmission electron microscopic examination. In the OVX-group, insignificant structural and biochemical changes were observed compared with the SC-group apart from the significantly increased lipid peroxides and decreased NO and catalase levels in serum. The H-group showed an elevated lipid peroxides and TNF-α levels, reduced catalase level, numerous degenerated Purkinje cells, vacuolations of the neuropil, some axonal degeneration, and few ghosts in the granular cell layer (GL). However, in OVX-H-group, oxidative stress, inflammation, and cerebellar damage were exacerbated and cerebellar estrogen was reduced associated with reduction in GL thickness and decreased Purkinje cells number. Most axoplasms had degenerated neurofilaments with abnormal myelination. The immunoexpression of glial fibrillary acidic protein were significantly increased in both OVX-group and H-group and significantly decreased in OVX-H group. Gene expression of AM and IL-10 were increased in cerebellar tissues of H-group compared with the SC-group but it was significantly decreased in OVX-H-group compared with H-group. Taken together, postmenopausal rats with hypertension suffered from structural cerebellar changes than rats with only hypertension or estrogen deficiency separately due to augmentation of the increased oxidative stress markers and the proinflammatory cytokines (TNF-α) with down regulation of the anti-inflammatory cytokine (IL-10) and the blood pressure regulator, AM. These suggested that high blood pressure is a critical factor for postmenopausal cerebellum.
Keywords: GFAP; IL-10; adrenomedullin; cerebellum; hypertension; postmenopause.
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