Increased Cx32 expression in spinal cord TrkB oligodendrocytes following peripheral axon injury

Abstract

Following injury to motor axons in the periphery, retrograde influences from the injury site lead to glial cell plasticity in the vicinity of the injured neurons. Following the transection of peripherally located preganglionic axons of the cervical sympathetic trunk (CST), a population of oligodendrocyte (OL) lineage cells expressing full length TrkB, the cognate receptor for brain derived neurotrophic factor (BDNF), is significantly increased in number in the spinal cord. Such robust plasticity in OL lineage cells in the spinal cord following peripheral axon transection led to the hypothesis that the gap junction communication protein connexin 32 (Cx32), which is specific to OL lineage cells, was influenced by the injury. Following CST transection, Cx32 expression in the spinal cord intermediolateral cell column (IML), the location of the parent cell bodies, was significantly increased. The increased Cx32 expression was localized specifically to TrkB OLs in the IML, rather than other cell types in the OL cell lineage, with the population of Cx32/TrkB cells increased by 59%. Cx32 expression in association with OPCs was significantly decreased at one week following the injury. The results of this study provide evidence that peripheral axon injury can differentially affect the gap junction protein expression in OL lineage cells in the adult rat spinal cord. We conclude that the retrograde influences originating from the peripheral injury site elicit dramatic changes in the CNS expression of Cx32, which in turn may mediate the plasticity of OL lineage cells observed in the spinal cord following peripheral axon injury.

Glial Gap Junction Pathology in the Spinal Cord of the 5xFAD Mouse Model of Early-Onset Alzheimer’s Disease

“…These divergent results may be explained by the fact that the CC1 + oligodendrocytes that were upregulated in the 5xFAD spinal cord likely do not share the same cell lineage identity as the CC1 + population that was found depleted in the brain of the 5xFAD model and could originate from heterogeneous polydendrocytes with differentiation capacity [ 63 , 64 ]. Interestingly, another study reported rapid proliferation of oligodendrocytes from a distinct type of TrkB oligodendrocyte lineage (OL), suggesting that glial cells in the spinal cord encounter different communication dynamics than those in the brain, and in response to peripheral traumatic injuries, they could be triggered to multiply [ 65 ]. These compelling findings indicate that in the same AD model, the oligodendroglial Gx47 GJs reflect a different and complex region-specific behavior that might imply the involvement of different regulatory pathways and signaling molecules driven by AD pathology.…”