Progesterone in conjunction with estradiol has neuroprotective effects in an animal model of neurodegeneration

Restorative and neuroprotective effects of the steroid hormones estradiol benzoate (EB) and progesterone (P) were investigated in an animal model of neurodegeneration. Rats received EB, P, EB + P, or vehicle/cholesterol control immediately after (Experiment 1) or prior to (Experiment 2) intrahippocampal colchicine infusions, which destroy hippocampal neurons and deplete neurotransmitters, such as acetylcholine. Intrahippocampal colchicine produced long latencies, distances, and increased wandering in the water maze, in addition to hippocampal damage. Chronic administration of hormones immediately after colchicine, which produced circulating concentrations within physiological range, did not affect water-maze performance compared to cholesterol control (Experiment 1). When acute EB (10 mu g SC) + P (500 mu g SC) was given prior to intrahippocampal colchicine, latencies, distances, and wandering in the water maze were reduced (Experiment 2). The acutely administered EB + P also were in physiological range. Both experiments demonstrate some influence of hormones on neuronal integrity and ChAT that warrants further investigation. Together, these findings suggest that physiological concentrations of EB + P, when administered before hippocampal damage, may have neuroprotective actions on learning and memory impairment and hippocampal damage. (C) 1999 Elsevier Science Inc.