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17α‐Oestradiol‐Induced Neuroprotection in the Brain of Spontaneously Hypertensive Rats
Author(s) -
Pietranera L.,
Brocca M. E.,
Roig P.,
Lima A.,
GarciaSegura L. M.,
De Nicola A. F.
Publication year - 2014
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12151
Subject(s) - endocrinology , medicine , dentate gyrus , aromatase , subgranular zone , neuroprotection , glial fibrillary acidic protein , astrocyte , vasopressin , hypothalamus , astrogliosis , ovariectomized rat , chemistry , hippocampus , estrogen , biology , central nervous system , neural stem cell , immunohistochemistry , genetics , stem cell , cancer , breast cancer , subventricular zone
17β‐oestradiol is a powerful neuroprotective factor for the brain abnormalities of spontaneously hypertensive rats (SHR). 17α‐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 17α‐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 μg pellet of 17α‐oestradiol dissolved in cholesterol or vehicle only for 2 weeks Normotensive Wistar–Kyoto (WKY) rats were used as controls. 17α‐Oestradiol did not modify blood pressure, serum prolactin, 17β‐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 17α‐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 17α‐oestradiol. These data indicate a role for 17α‐oestradiol as a protective factor for the treatment of hypertensive encephalopathy. Furthermore, 17α‐oestradiol is weakly oestrogenic in the periphery and can be used in males.