Distribution and localization patterns of estrogen receptor-beta and insulin-like growth factor-1receptors in neurons and glial cells of the female rat substantia nigra: Localization of ERbeta and IGF-1R in substantia nigra.

QUESADA, A., ROMEO, H. E., AND MICEVYCH, P.E.

JOURNAL OF COMPARATIVE NEUROLOGY

Año: 2007 vol. 503 p. 198 - 208

0021-9967

Although several studies have focused on the neuroprotective effects of estrogen (E2) on stroke, there have been tantalizing reports on the potential neuroprotective role of E2 in degenerative neuronal diseases such as Alzheimer´s and Parkinson´s (PD). In animal models of PD, E2 protects the nigrostriatal dopaminergic (DA) system against neurotoxins. However, little is known about the cellular and molecular mechanism(s) involved by which E2 elicits its neuroprotective effects on the nigrostriatal DA system. A preferred mechanism for neuroprotection is the interaction of E2 with specific neuroprotective growth factors and receptors. One such neuroprotective factor/receptor system is insulin-like growth factor-1 (IGF-1). E2 neuroprotective effects in the substantia nigra (SN) DA system have been shown to be dependent on IGF-1. To determine whether E2 also interacts with the IGF-1 receptor (IGF-1R) and to determine the cellular localization of estrogen receptor (ER) and IGF-1R, we compared the distribution of ER and IGF-1R in the SN. Stereological measurements revealed that 40% of the subpopulation of tyrosine hydroxylase-immunoreactive (TH-ir) SN pars compacta (SNpc) DA neurons are immunoreactive for estrogen receptor-beta (ERbeta). No immunolabeling for ERalpha was observed. In situ hybridization and immunocytochemistry studies confirmed the expression of IGF-1R mRNA and revealed that almost all TH-ir SNpc DA neurons were immunoreactive for IGF-1R, respectively. Moreover, one-third of glial fibrillary acidic protein (GFAP-ir) cells in the SN were ERbeta-ir, and 67% of GFAP-ir cells expressed IGF-1R-ir. Therefore, the localization of ERbeta and IGF-1R on SNpc DA neurons and astrocytes suggests a modulatory role of E2 on IGF-1R, and this modulation may affect neuroprotection.