Glial Response to Oligodendrocytic Connexin Knockout Within the Murine Central Nervous System
thesisposted on 01.08.2020, 00:00 by Samantha Ann Keil
Connexin proteins are crucial for gap junction formation and cell-cell communication within the central nervous system (CNS). Mutations to oligodendrocytic connexin 32 (Cx32) and connexin 47 (Cx47) cause the inherited neuropathies X-Linked Charcot-Marie-Tooth Disease and Pelizaeus Merzbacher Like Disease 1, respectively. However, the contribution of Cx32 and Cx47 to CNS disease phenotypes, particularly regarding oligodendrocyte development and glial cell communication, remains understudied. In this study, we found that although the loss of either connexin results in both dysregulated oligodendrocyte development and surrounding glial activation, there are responses specific to each Cx knockout. The loss of Cx32 in the CNS causes a significant upregulation in Iba1+ microglia and transcriptional alterations suggestive of developmental, rather than overtly pro-inflammatory regulation. Comparatively, the loss of Cx47 results in a significant decrease in oligodendrocyte viability, with astrocytic and microglial activation and transcript alterations suggestive of an injury response regulated by factors within the MEK/ERK pathway. Together suggesting that these Cxs play a crucial role in the oligodendrocytic function and surrounding glial communication necessary to maintain homeostasis within the CNS.