Traumatic brain injury-associated microglia adopt longitudinal transcriptional changes consistent with long-term depression of synaptic strength

Makinde, H. M.; Just, T. B.; Winter, D. R.; Schwulst, S. J.

doi:10.1101/422071

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bioRxiv · 10.1101/422071

Traumatic brain injury-associated microglia adopt longitudinal transcriptional changes consistent with long-term depression of synaptic strength

Makinde, H. M.·Just, T. B.·Winter, D. R.·Schwulst, S. J.

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Abstract

Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injury, or concussions, may lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this subsequent neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. In the current study we hypothesized that TBI-associated microglia would adopt longitudinal changes in their transcriptional profile associated with pathways linked to the development of motor, cognitive, and behavioral disorders. C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to RNA-sequencing at 7, 30, and 90 days post-injury. We identified 4 major patterns of gene expression corresponding to the host defense response, synaptic potentiation, lipid remodeling, and membrane polarization. In particular, significant upregulation of genes involved in long-term synaptic potentiation including Ptpn5, Shank3, and Sqstm1 were observed offering new insight into a previously unknown role of microglia in the weakening of synaptic efficacy between neurons after brain injury.

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Makinde, H. M., Just, T. B., Winter, D. R., Schwulst, S. J.. 2018-09-19. Traumatic brain injury-associated microglia adopt longitudinal transcriptional changes consistent with long-term depression of synaptic strength. https://doi.org/10.1101/422071

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