Targeting microglia attenuates neuroinflammation ‐related neural damage in mice carrying human PLP1 mutations

Main PointsTreatment ofPLPmut mice with PLX3397 (150  ppm in chow)• depletes microglia of the CNS;• reduces neuroinflammation by T‐lymphocytes;• attenuates axon and myelin degeneration, neuron loss, and retinal thinning. AbstractGenetically caused neurological disorders of the central nervous system (CNS) usually result in poor or even fatal clinical outcome and few or no causative treatments are available. Often, these disorders are associated with disease ‐amplifying neuroinflammation, a feature shared by progressive forms of multiple sclerosis (PMS), another poorly treatable disorder of the CNS. We have previously generated two mouse lines carrying distinct mutations in the oligodendrocyticPLP1 gene that have initially been identified in patients fulfilling clinical criteria for multiple sclerosis (MS). These mutations cause a loss of function of the gene product resulting in a histopathological and clinical phenotype common to both PMS and genetic CNS disorders, like hereditary spastic paraplegias. Importantly, neuroinflammation comprising adaptive immune reactions promotes disease progression in thesePLP1 mutant models, opening the possibility to improve disease outcome of the respective disorders by targeting/modulating inflammation. We here show that PLX3397, a potent inhibitor of the CSF ‐1R and targeting innate immune cells, attenuates neuroinflammation in our models by reducing numbers of resident microglia and attenuating T‐lymphocyte recruitm...

Source: Glia - November 22, 2018 Category: Neurology Authors: Janos Groh, Dennis Klein, Kristina Berve, Brian L. West, Rudolf Martini Tags: RESEARCH ARTICLE Source Type: research