Elsevier

Neuroscience

Volume 96, Issue 1, January 2000, Pages 41-49
Neuroscience

Estrogen binding and estrogen receptor characterization (ERα and ERβ) in the cholinergic neurons of the rat basal forebrain

https://doi.org/10.1016/S0306-4522(99)00520-5Get rights and content

Abstract

Estrogen is thought to enhance cognitive functions by modulating the production of acetylcholine in basal forebrain neurons; a system that projects to the cerebral cortex and hippocampus and plays a central role in learning and memory. To elucidate the mechanism of estrogen action in the cholinergic system, we utilized a combined in vivo autoradiography/immunocytochemistry technique to evaluate the distribution of estrogen binding sites in cholinergic neurons of the rat basal forebrain. The results of these studies revealed that a portion of the cholinergic neurons in the medial septum (41%), vertical (32%) and horizontal (29%) limbs of the diagonal band and in the substantia innominata/nucleus basalis (4%) contained estrogen receptors. Through the use of a double-label in situ hybridization/immunocytochemistry technique we have shown that estrogen receptor-α is the predominant estrogen receptor in the cholinergic neurons, with only a few cells containing estrogen receptor-β.

The results of these studies provide evidence that biologically active estrogen receptors are present in the basal forebrain cholinergic neurons of the adult rat brain, with estrogen receptor-α being the predominant receptor subtype. The demonstration that cholinergic neurons contain estrogen receptors is consistent with the possibility that estrogen directly modulates the activity of cholinergic neurons in rats and may provide insight as to how estrogen improves cognitive functions in women.

Section snippets

Materials

125I-estrogen (17α-iodovinyl-11β-methoxyestradiol) was obtained from the custom iodination (NEN; Boston, MA, U.S.A.) of E-17-tributylstannyvinyl-11-methoxy-estradiol (RAXL Enterprises; Newton, MA, U.S.A.) as described previously.17

Animals

In the 125I-estrogen binding studies described below, ovariectomized rats were used because endogenous estrogens would compete with the radiolabeled ligand and potentially mask estrogen binding sites. Rats used for the double-label in situ

In vivo binding/immunocytochemistry studies

The present study used 17α-iodovinyl-11β-methoxyestradiol (125I-estrogen), a new radiolabeled estrogen, for in vivo binding studies because this compound has recently been shown to: (i) have a similar binding affinity for both ERα and ERβ in vitro and in vivo; (ii) be selective for ERs; (iii) be slowly metabolized and; (iv) exhibit a good signal–noise profile in vivo.17., 33. Through the use of a double-label in vivo binding/immunocytochemistry technique, the co-localization of estrogen

Discussion

The results of the present co-localization studies have demonstrated that ChAT neurons in the rat basal forebrain nuclei contain a biologically active ER and shown that ERα is the predominant ER in these ChAT neurons. Through the use of a combined in vivo autoradiography/immunocytochemistry technique, we found that 22–41% of the ChAT neurons in the medial septum and diagonal band of Broca had a nuclear uptake and retention of radiolabeled estrogen (125I-estrogen), while only 4% of the ChAT

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