title: Changes in interneuronal phenotypes regulated by estradiol in the adult rat hippocampus: a potential role for neuropeptide Y.
abstract: Ovarian hormones regulate pyramidal cell synapse formation and excitability and interneuronal GABAergic tone in the CA1 region of the adult female rat hippocampus. The role of 17beta-estradiol in these effects is complex and appears to involve a subset of hippocampal interneurons, which express different calcium-binding protein and neuropeptide phenotypes and nuclear estrogen receptor alpha. We found that, in the hippocampus, nuclear estrogen receptor alpha-immunoreactive interneurons co-express neuropeptide Y, calbindin-D28k and calretinin but do not parvalbumin or cholecystokinin. Moreover, a proportion of neuropeptide Y-immunoreactive interneurons co-expresses calbindin-D28k and calretinin. This pattern is similar in the presence or absence of 17beta-estradiol treatment in ovariectomized rats. We then used immunohistochemistry and in situ hybridization to determine whether 17beta-estradiol treatment regulates expression of CA1 interneuronal phenotypic markers via nuclear estrogen receptor alpha activation. We found that 17beta-estradiol treatment of ovariectomized rats increased neuropeptide Y mRNA levels (25%) and the neuropeptide Y mRNA-associated grain density per cell (11%), as well as the number of neuropeptide Y-immunoreactive cells (11%), predominantly in the pyramidal cell layer (stratum pyramidale). Treatment with CI628, a selective estrogen response modulator that acts as an antagonist for nuclear estrogen receptor, blocked 17beta-estradiol-induced increase of neuropeptide Y mRNA levels. 17beta-Estradiol treatment did not alter the number of parvalbumin, calretinin, and cholecystokinin immunoreactive cells, nor mRNA levels for parvalbumin and cholecystokinin. Therefore, the present study has identified neuropeptide Y expression as the main interneuronal phenotype that co-expresses nuclear estrogen receptor alpha and shown that neuropeptide Y is responsive to 17beta-estradiol in CA1 pyramidal cell layer. We suggest that 17beta-estradiol may regulate neuropeptide Y expression mediated by nuclear estrogen receptor alpha-dependent activation in a subset of hippocampal interneurons, and we speculate that subsequent neuropeptide Y release may indirectly contribute to regulate glutamate-dependent neuronal activity in the adult rat hippocampus.
authors.affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, Box 165, 1230 York Avenue, New York, NY 10021-6399, USA. nakamun@rockefeller.edu
authors.forename: N H
authors.initials: NH
authors.lastname: Nakamura
authors.forename: B S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D009594:Nitromifene / Q000494:pharmacology; D010052:Ovariectomy; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D047628:Estrogen Receptor alpha; D009478:Neuropeptide Y; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol; D009594:Nitromifene