Expression of estrogen receptor α and β in reactive astrocytes at the male rat hippocampus after status epilepticus

Abstract

Estrogen is neuroprotective against status epilepticus (SE)-induced hippocampal damage in female animals. In male animals, estrogen is converted from testosterone via aromatization the activity of which is upregulated by brain damage. However, it is controversial whether estrogen is neuroprotective or neuroinvasive against male hippocampal damage after SE. In order to understand the role of estrogen, it is important to elucidate the distribution manner of estrogen receptor (ER)alpha and beta as the targets of estrogen. In this study, we examined the time course changes of ERs in adult male rat hippocampus after SE using anti-ERalpha antibodies (MC-20 and PA1-309) and anti-ERbeta antibodies (PA1-310B and PA1-311). In control rats, both ERalpha and beta were expressed in the pyramidal cells predominantly at CA1 and CA3. ERalpha was expressed in the cytoplasm and the nucleus, whereas ERbeta was expressed in the cytoplasm of the pyramidal cells. After SE, according to the pyramidal cell loss at CA1, the number of ERalpha- and beta-immunoreactive pyramidal cells decreased up to day 21. On the other hand, reactive astrocytes, which newly appeared after SE and formed gliosis at CA1, were confirmed to express both ERs in the nucleus, cytoplasm, and process. There were no differences in immunoreactivity between antibodies. Our results indicate that endogenous estrogen affects the pyramidal cells through ERalpha and beta under normal circumstances in adult male rats, whereas the targets of estrogen shift to the reactive astrocytes through ERalpha and beta after SE.

Frontier of Epilepsy Research - mTOR signaling pathway

“…Their expression in CA1 and CA3 pyramidal neurons is decreased in kainate-induced acute seizure. In contrast, it appears in the gliotic reactive astrocytes in CA1 (Sakuma et al, 2009). In female animals, estrogen is neuroprotective against SE-induced neuronal damage in the hippocampus (Reibel et al, 2000).…”

“…The mTOR pathway is activated in reactive astrocytes in spinal cord injury (Codeluppi et al, 2009). The levels of ERα in CA1 astrocytes and PLD were increased in KA model Sakuma et al, 2009). ERK/MAPK is activated in mechanical trauma-induced astrogliosis and human reactive astrocytes (Mandell and VandenBerg, 1999;Mandell et al, 2001).…”

Neurodegenerative Diseases, Sex Differences and the 27 kDa Heat Shock Protein in the Nervous System

“…In the male rat hippocampus, ER-α immunoreactivity is predominantly in the nuclei of pyramidal cells of the CA1 and CA3 regions (Sakuma et al 2009 ).…”

“…Furthermore, ER-β immunoreactivity is localized in the cytoplasm, dendritic spines, dendrites, axons and axon terminals of pyramidal and granule cells (Azcoitia et al 1999 ;Milner et al 2005 ;Sakuma et al 2009 ).…”

“…In female rats, ER-α is also found in astrocytes throughout the hippocampus . In male rats, the ER-α is primarily located in pyramidal cells in the CA1 and CA2 regions of the hippocampus (Azcoitia et al 1999 ;Milner et al 2001Milner et al , 2005Sakuma et al 2009 ).…”