Infection with herpesviridae in pregnant dams alters midbrain dopaminergic signatures in adult offspring

The adult offspring of MHV68 infected dams had a significantly decreased expression of genes linked to dopamine neurons (Th, lmx1b, and foxa1). Deconvolution analysis revealed that the proportion of dopamine neurons in the midbrain was reduced. Pathway analyses indicated mitochondrial dysfunction, with reductions in genes associated with ATP synthesis, mitochondrial respiratory chain, and mitochondrial translation in the offspring of dams infected with MHV68. TIGAR (a negative regulator of mitophagy) and SDHA (mitochondrial complex II subunit) protein levels were increased, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum were increased in these offspring. No such changes were observed in the offspring of dams infected with MCMV. Pregnant dams were injected with murine cytomegalovirus (MCMV), murine gamma herpes virus (MHV68) or phosphate buffered saline (PBS) at embryonic day 8.5. The young adult offspring were sacrificed at eight weeks of age, and their midbrains processed for unbiased whole genome RNA sequencing as well as targeted protein expression and high-performance liquid chromatography of dopamine and its metabolites.