Maternal immune activation modifies the course of Niemann-pick disease, type C1 in a gender specific manner

Publication date: Available online 17 October 2019Source: Molecular Genetics and MetabolismAuthor(s): Antony Cougnoux, Mason Fellmeth, Tansy Gu, Cristin D. Davidson, Alana L. Gibson, William J. Pavan, Forbes D. PorterAbstractNiemann-Pick disease, type C1 (NPC1) is a rare neurodegenerative lysosomal storage disease with a wide spectrum of clinical manifestation. Multiple genetic factors influence the NPC1 mouse phenotype, but very little attention has been given to prenatal environmental factors that might have long-term effects on the neuroinflammatory component of NPC1 pathology. Studies in other mouse models of cerebellar ataxia have shown that developmental exposures lead to Purkinje neuron degeneration later in life, suggesting that environmental exposures during development can impact cerebellar biology. Thus, we evaluated the potential effect of maternal immune activation (MIA) on disease progression in an Npc1 mouse model. The MIA paradigm used mimics viral infection using the toll like receptor 3 agonist polyinosinic-polycytidilic acid during gestation. Through phenotypic and pathologic tests, we measured motor and behavioral changes as well as cerebellar neuroinflammation and neurodegeneration. We observed a gender and genotype dependent effect of MIA on the cerebellum. While the effects of MIA have been previously shown to primarily affect male progeny, we observed increased sensitivity of female mutant progeny to prenatal exposure to treatment with polyinosinic-pol...
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research