Microglia promote remyelination independent of their role in clearing myelin debris.

Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss. While therapies exist to slow MS progression, no treatment currently exists for remyelination. Remyelination, linked to reduced disability in MS, relies on microglia and monocyte-derived macrophages (MDMs). This study aims to understand the role of microglia during remyelination by lineage tracing and depleting them. Microglial lineage tracing reveals that both microglia and MDMs initially accumulate, but microglia later dominate the lesion. Microglia and MDMs engulf equal amounts of inhibitory myelin debris, but after microglial depletion, MDMs compensate by engulfing more myelin debris. Microglial depletion does, however, reduce the recruitment and proliferation of oligodendrocyte progenitor cells (OPCs) and impairs their subsequent differentiation and remyelination. These findings underscore the essential role of microglia during remyelination and offer insights for enhancing this process by understanding microglial regulation of remyelination.

Evidence of altered metabolism of cellular membranes in bipolar disorder comorbid with post-traumatic stress disorder.

In proton magnetic resonance spectroscopy (¹H MRS) studies, aberrant levels of choline-containing compounds that include glycerophosphocholine plus phosphocholine (GPC+PC), can signify alterations in the metabolism of cellular membrane phospholipids (MPLs) from a healthy baseline. In a recent ¹H MRS study, we reported increased GPC+PC in cortical and subcortical areas of adult patients with bipolar disorder I (BP-I). Post-traumatic stress disorder (PTSD) can worsen the severity of BP-I, but it is unclear whether the effect of a PTSD comorbidity in BP-I is associated with altered MPL metabolism. The purpose of this study was to re-investigate the ¹H MRS data to determine whether the regional extent of elevated GPC+PC was greater in BP-I patients with PTSD (BP-I/wPTSD) compared to BP-I without comorbid PTSD (BP-I/woPTSD) patients and healthy controls. GPC+PC levels from four brain areas [the anterior cingulate cortex (ACC), anterior-dorsal ACC, caudate, and putamen] were measured in 14 BP-I/wPTSD, 36 BP-I/woPTSD, and 44 healthy controls using a multi-voxel 1H MRS approach on a 3 Tesla system with high spatial resolution and absolute quantification. Results show a significant increase in GPC+PC levels from the caudate and putamen of BP-I/wPTSD patients compared to healthy controls (P<0.05) and in the putamen compared to BP-I/woPTSD patients (P<0.05). These findings are consistent with evidence of elevated degradation of MPLs in the neuropil that is more pronounced in BP-I patients with comorbid PTSD.