PMID- 24730417 OWN - NLM STAT- MEDLINE DCOM- 20141208 LR - 20211203 IS - 1365-2826 (Electronic) IS - 0953-8194 (Linking) VI - 26 IP - 5 DP - 2014 May TI - 17alpha-Oestradiol-induced neuroprotection in the brain of spontaneously hypertensive rats. PG - 310-20 LID - 10.1111/jne.12151 [doi] AB - 17beta-oestradiol is a powerful neuroprotective factor for the brain abnormalities of spontaneously hypertensive rats (SHR). 17alpha-Oestradiol, a nonfeminising isomer showing low affinity for oestrogen receptors, is also endowed with neuroprotective effects in vivo and in vitro. We therefore investigated whether treatment with 17alpha-oestradiol prevented pathological changes of the hippocampus and hypothalamus of SHR. We used 20-week-old male SHR with a blood pressure of approximately 170 mmHg receiving s.c. a single 800 mug pellet of 17alpha-oestradiol dissolved in cholesterol or vehicle only for 2 weeks Normotensive Wistar-Kyoto (WKY) rats were used as controls. 17alpha-Oestradiol did not modify blood pressure, serum prolactin, 17beta-oestradiol levels or the weight of the testis and pituitary of SHR. In the brain, we analysed steroid effects on hippocampus Ki67+ proliferating cells, doublecortin (DCX) positive neuroblasts, glial fibrillary acidic protein (GFAP)+ astrocyte density, aromatase immunostaining and brain-derived neurotrophic factor (BDNF) mRNA. In the hypothalamus, we determined arginine vasopressin (AVP) mRNA. Treatment of SHR with 17alpha-oestradiol enhanced the number of Ki67+ in the subgranular zone and DCX+ cells in the inner granule cell layer of the dentate gyrus, increased BDNF mRNA in the CA1 region and gyrus dentatus, decreased GFAP+ astrogliosis in the CA1 subfield, and decreased hypothalamic AVP mRNA. Aromatase expression was unmodified. By contrast to SHR, normotensive WKY rats were unresponsive to 17alpha-oestradiol. These data indicate a role for 17alpha-oestradiol as a protective factor for the treatment of hypertensive encephalopathy. Furthermore, 17alpha-oestradiol is weakly oestrogenic in the periphery and can be used in males. CI - (c) 2014 British Society for Neuroendocrinology. FAU - Pietranera, L AU - Pietranera L AD - Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina. FAU - Brocca, M E AU - Brocca ME FAU - Roig, P AU - Roig P FAU - Lima, A AU - Lima A FAU - Garcia-Segura, L M AU - Garcia-Segura LM FAU - De Nicola, A F AU - De Nicola AF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neuroendocrinol JT - Journal of neuroendocrinology JID - 8913461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dcx protein, rat) RN - 0 (Doublecortin Protein) RN - 0 (Neuroprotective Agents) RN - 113-79-1 (Arginine Vasopressin) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Arginine Vasopressin/metabolism MH - Blood Pressure/drug effects MH - Brain/*drug effects MH - Brain Chemistry/drug effects MH - Brain-Derived Neurotrophic Factor/metabolism MH - Doublecortin Protein MH - Estradiol/*pharmacology MH - Gliosis/pathology MH - Male MH - Neurogenesis/drug effects MH - Neuroprotective Agents/*pharmacology MH - Rats MH - Rats, Inbred SHR MH - Rats, Inbred WKY OTO - NOTNLM OT - hippocampus OT - hypertension OT - hypothalamus OT - oestrogens EDAT- 2014/04/16 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/04/16 06:00 PHST- 2013/12/02 00:00 [received] PHST- 2014/02/20 00:00 [revised] PHST- 2014/03/16 00:00 [accepted] PHST- 2014/04/16 06:00 [entrez] PHST- 2014/04/16 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - 10.1111/jne.12151 [doi] PST - ppublish SO - J Neuroendocrinol. 2014 May;26(5):310-20. doi: 10.1111/jne.12151.