Differential expression of estrogen receptors alpha and beta in the spinal cord during postnatal development: localization in glial cells

Estrogens are recognized as neuroprotective and neurotrophic agents in the central nervous system. They are involved in neuronal differentiation and survival and promote neural development. Estrogen receptors alpha (ER-alpha) and beta (ER-beta) are predominantly expressed in neurons, whereas their presence in glial cells in vivo is more controversial. Changes in their expression during development have been described in different brain areas, but little is known about their presence in the spinal cord. We have carried out an immunohistochemical study in an attempt to analyze the expression of both ERs in astrocytes and oligodendrocytes of the rat spinal cord and their modifications during postnatal development. RT-PCR analysis of whole spinal cord extracts from 4-, 12-, and 25-day-old and adult rats indicated changes in the expression of both receptors during maturation. Immunohistochemistry of slices of the lumbar tract revealed that in an area of the ventral spinal cord that does not contain neuronal cell bodies, but mainly fibers and glial cells, both ER-alpha and ER-beta can be detected. Immunostaining is clearly nuclear, and, in the case of ER-alpha, both markedly positive and weakly labeled cells can be identified. ER-alpha is expressed during early development to progressively decline in the adult stage. In contrast, the ER-beta signal is low and peaks at postnatal day 25, whereas it is almost undetectable at other ages. Colocalization studies revealed that, at postnatal day 25, ER-alpha and ER-beta are expressed in astrocytes (identified by the specific marker glial fibrillar acidic protein) and oligodendrocytes (labeled by antimyelin 2',3'-cyclic nucleotide 3'-phosphodiesterase). The present results confirm the expression of ER-alpha and ER-beta in glial cells in vivo and suggest that, also in the spinal cord, glial cells may contribute to the effects of estrogen during development.