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Aging and substitutive hormonal therapy influence in regional and subcellular distribution of ERα in female rat brain

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Abstract

Estrogens are not only critical for sexual differentiation it is well-known for the role of 17β-estradiol (E2) in the adult brain modulating memory, learning, mood and acts as a neuroprotector. E2 exerts its actions through two classical receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). The distribution of both receptors changes from one brain area to another, E2 being able to modulate their expression. Among the classical features of aging in humans, we find cognitive impairment, dementia, memory loss, etc. As estrogen levels change with age, especially in females, it is important to know the effects of low E2 levels on ERα distribution; results from previous studies are controversial regarding this issue. In the present work, we have studied the effects of long-term E2 depletion as well as the ones of E2 treatment on ERα brain distribution of ovariectomized rats along aging in the diencephalon and in the telencephalon. We have found that ovariectomy causes downregulation and affects subcellular localization of ERα expression during aging, meanwhile prolonged estrogen treatment produces upregulation and overexpression of the receptor levels. Our results support the idea of the region-specific neuroprotection mechanisms mediated by estradiol.

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Abbreviations

Au Cx:

Auditory cortex

CA:

Cornu Amonis region

CNS:

Central nervous system

DAB:

Diaminobenzidine

E2:

17β-estradiol

ERα:

Estrogen receptor alpha

ERβ:

Estrogen receptor beta

H2O2 :

hydrogen peroxide

M Cx:

Motor cortex

MDN:

Medial dorsal nucleus

M Hb:

Medial habenular nucleus

MPA:

Medial preoptic area

O Cx:

Olfactory cortex

PBS:

Phosphate-buffered saline

PVN:

Paraventricular nucleus

RIA:

Radioimmuno assay

S Cx:

Sensorial cortex

SON:

Supraoptic nucleus

V Cx:

Visual cortex

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Acknowledgments

This work was supported by MEC and FEDER SAF2007-64076 grants; FIS PI020324 grant and MEC grants AP20040854, AP20053815, and FICYT grant BP05-064 to CP, EM, and CO.

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Authors and Affiliations

  1. Department of Morphology, Cellular Biology Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain

    Ana Navarro, Eva del Valle, Cristina Pérez & Jorge Tolivia

  2. Department of Functional Biology–Physiology Area, University of Oviedo, Oviedo, Spain

    Ana Alonso & Celestino González

  3. Área de Neurociencias, CIMA, Avda. Pío XII, 55 31008, Pamplona, Spain

    Cristina Ordóñez & Eva Martínez

  4. Dpto. Morfología y Biología Celular, 8ª Planta Facultad de Medicina, Universidad de Oviedo, c/Julián Clavería s/n, Oviedo, 33006, Spain

    Jorge Tolivia

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  1. Ana Navarro
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  2. Eva del Valle
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  3. Cristina Ordóñez
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  4. Eva Martínez
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  8. Jorge Tolivia
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Correspondence to Jorge Tolivia.

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Navarro, A., del Valle, E., Ordóñez, C. et al. Aging and substitutive hormonal therapy influence in regional and subcellular distribution of ERα in female rat brain. AGE 35, 821–837 (2013). https://doi.org/10.1007/s11357-012-9415-9

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