Estrogen receptors observed at extranuclear neuronal sites and in glia in the nucleus accumbens core and shell of the female rat: Evidence for localization to catecholaminergic and GABAergic neurons

Estrogens affect dopamine‐dependent diseases/behavior and have rapid effects on dopamine release and receptor availability in the nucleus accumbens (NAc). Low levels of nuclear estrogen receptor (ER) α and ERβ are seen in the NAc, which cannot account for the rapid effects of estrogens in this regio...

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Bibliographic Details
Published in:Journal of comparative neurology (1911) 2022-08, Vol.530 (11), p.2056-2072
Main Authors: Almey, Anne, Milner, Teresa A., Brake, Wayne G.
Format: Article
Language:English
Subjects:
Animals
Axons
Catecholamines
Caudate-putamen
Dendrites
Dopamine
Dopamine - metabolism
Electron microscopy
estrogen receptor alpha
Estrogen Receptor alpha - metabolism
estrogen receptor beta
Estrogen Receptor beta - metabolism
Estrogen receptors
Estrogens
Estrogens - metabolism
Female
GABAergic Neurons - metabolism
gamma-Aminobutyric Acid - metabolism
G‐protein coupled estrogen receptor 1
Localization
Neostriatum
Neuroglia - metabolism
Neuronal-glial interactions
Nucleus accumbens
Nucleus Accumbens - metabolism
Presynapse
Rats
Receptors, Estrogen - metabolism
ventral striatum
γ-Aminobutyric acid
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Summary:Estrogens affect dopamine‐dependent diseases/behavior and have rapid effects on dopamine release and receptor availability in the nucleus accumbens (NAc). Low levels of nuclear estrogen receptor (ER) α and ERβ are seen in the NAc, which cannot account for the rapid effects of estrogens in this region. G‐protein coupled ER 1 (GPER1) is observed at low levels in the NAc shell, which also likely does not account for the array of estrogens’ effects in this region. Prior studies demonstrated membrane‐associated ERs in the dorsal striatum; these experiments extend those findings to the NAc core and shell. Single‐ and dual‐immunolabeling electron microscopy determined whether ERα, ERβ, and GPER1 are at extranuclear sites in the NAc core and shell and whether ERα and GPER1 were localized to catecholaminergic or γ‐aminobutyric acid‐ergic (GABAergic) neurons. All three ERs are observed, almost exclusively, at extranuclear sites in the NAc, and similarly distributed in the core and shell. ERα, ERβ, and GPER1 are primarily in axons and axon terminals suggesting that estrogens affect transmission in the NAc via presynaptic mechanisms. About 10% of these receptors are found on glia. A small proportion of ERα and GPER1 are localized to catecholaminergic terminals, suggesting that binding at these ERs alters release of catecholamines, including dopamine. A larger proportion of ERα and GPER1 are localized to GABAergic dendrites and terminals, suggesting that estrogens alter GABAergic transmission to indirectly affect dopamine transmission in the NAc. Thus, the localization of ERs could account for the rapid effects of estrogen in the NAc. This study used electron microscopy to examine the distribution ERα, ERβ, and GPER1 in the nucleus accumbens (Nac) core and shell. These receptors are localized, almost exclusively, to extranuclear sites in the NAc. They are observed in all neuronal profiles and in glia, but are most prevalent in presynaptic profiles. A small proportion of ERα and GPER1 are localized to catecholaminergic neurons, and a larger proportion are localized to GABAergic neurons. These results provide a mechanism for the rapid effects of estrogens on dopaminergic transmission in the NAc.
ISSN:0021-9967
1096-9861
DOI:10.1002/cne.25320