| First Author | Spence RD | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 26 | Pages | 10924-33 |
| PubMed ID | 23804112 | Mgi Jnum | J:199634 |
| Mgi Id | MGI:5504296 | Doi | 10.1523/JNEUROSCI.0886-13.2013 |
| Citation | Spence RD, et al. (2013) Estrogen mediates neuroprotection and anti-inflammatory effects during EAE through ERalpha signaling on astrocytes but not through ERbeta signaling on astrocytes or neurons. J Neurosci 33(26):10924-33 |
| abstractText | Estrogens can signal through either estrogen receptor alpha (ERalpha) or beta (ERbeta) to ameliorate experimental autoimmune encephalomyelitis (EAE), the most widely used mouse model of multiple sclerosis (MS). Cellular targets of estrogen-mediated neuroprotection are still being elucidated. Previously, we demonstrated that ERalpha on astrocytes, but not neurons, was critical for ERalpha ligand-mediated neuroprotection in EAE, including decreased T-cell and macrophage inflammation and decreased axonal loss. Here, we determined whether ERbeta on astrocytes or neurons could mediate neuroprotection in EAE, by selectively removing ERbeta from either of these cell types using Cre-loxP gene deletion. Our results demonstrated that, even though ERbeta ligand treatment was neuroprotective in EAE, this neuroprotection was not mediated through ERbeta on either astrocytes or neurons and did not involve a reduction in levels of CNS inflammation. Given the differential neuroprotective and anti-inflammatory effects mediated via ERalpha versus ERbeta on astrocytes, we looked for molecules within astrocytes that were affected by signaling through ERalpha, but not ERbeta. We found that ERalpha ligand treatment, but not ERbeta ligand treatment, decreased expression of the chemokines CCL2 and CCL7 by astrocytes in EAE. Together, our data show that neuroprotection in EAE mediated via ERbeta signaling does not require ERbeta on either astrocytes or neurons, whereas neuroprotection in EAE mediated via ERalpha signaling requires ERalpha on astrocytes and reduces astrocyte expression of proinflammatory chemokines. These findings reveal important cellular differences in the neuroprotective mechanisms of estrogen signaling through ERalpha and ERbeta in EAE. |
