Modulation of tyrosine receptor imposed by Estrogen in Memory and Cognition in Female Rats.

Abstract

The present study aimed to investigate the potential role of estrogen in modulating the pathogenesis of dementia-type-AD phenotype, possibly by tyrosine kinase. Female Wistar rats were ovariectomized (OVX) and were treated with Diethylstilbesterol (DES), an estrogen analogue (20μg/kg/day, i.m.), and Imatinib, a tyrosine kinase inhibitor (30mg/kg/day, orally), for two months. Animals underwent surgical ovariectomy exhibited significant memory deficits in spatial memory assessment as mean dwell time, short-term memory as spontaneous alteration, and novel object recognition after a chronic period of 4 weeks. OVX animals administered with DES produced significant restoration of memory dysfunction in comparison to OVX, as exhibited by Morris water maze (p=0.0003), Y maze (p<0.0001), and NORT. Imatinib prior to DES treatment in OVX animals showed significant decline in memory functions, which confirms the potential involvement of tyrosine receptor kinase activity in improved memory functions offered by estrogen. Levels of estradiol were significantly (p<0.0001) lower in the OVX group compared to normal which was significantly (p<0.0001) restored in the OVX+E group. Biochemical estimations of TBARS, glutathione, and acetylcholinesterase levels in the brain showed a significant increase in oxidative stress among the OVX group. However, a significant restoration of oxidative changes with TBARS (p=0.0496), glutathione (p<0.0001), and acetylcholinesterase activity (p=0.0201) of OVX animals receiving DES was observed in comparison to animals receiving imatinib followed by DES. These implications in the brain signify that estrogen and tyrosine kinase play an important role in the pathogenesis of dementia. In conclusion, estrogen offers neurochemical mediation for cognition and memory possibly via modulation of tyrosine kinase signaling in female subjects.