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 17β-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 α. We found that, in the hippocampus, nuclear estrogen receptor α-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 17β-estradiol treatment in ovariectomized rats. We then used immunohistochemistry and in situ hybridization to determine whether 17β-estradiol treatment regulates expression of CA1 interneuronal phenotypic markers via nuclear estrogen receptor α activation. We found that 17β-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 17β-estradiol-induced increase of neuropeptide Y mRNA levels. 17β-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 α and shown that neuropeptide Y is responsive to 17β-estradiol in CA1 pyramidal cell layer. We suggest that 17β-estradiol may regulate neuropeptide Y expression mediated by nuclear estrogen receptor α-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.