AAH2 gene is not required for dopamine-dependent neurochemical and behavioral abnormalities produced by Toxoplasma infection in mouse

R McFarland, ZT Wang, Y Jouroukhin, Y Li… - Behavioural brain …, 2018 - Elsevier
R McFarland, ZT Wang, Y Jouroukhin, Y Li, O Mychko, I Coppens, J Xiao, L Jones-Brando…
Behavioural brain research, 2018Elsevier
Infection with the protozoan parasite, Toxoplasma gondii (T. gondii), has been associated
with the increased risk for several psychiatric disorders. The exact mechanisms of a
hypothesized contribution of T. gondii infection are poorly understood. The T. gondii genome
contains two aromatic amino acid hydroxylase genes (AAH1 and AAH2) that encode
proteins that can produce L-DOPA. One popular hypothesis posits that these encoded
enzymes might influence dopamine (DA) production and hence DA synaptic transmission …
Abstract
Infection with the protozoan parasite, Toxoplasma gondii (T. gondii), has been associated with the increased risk for several psychiatric disorders. The exact mechanisms of a hypothesized contribution of T. gondii infection are poorly understood. The T. gondii genome contains two aromatic amino acid hydroxylase genes (AAH1 and AAH2) that encode proteins that can produce L-DOPA. One popular hypothesis posits that these encoded enzymes might influence dopamine (DA) production and hence DA synaptic transmission, leading to neurobehavioral abnormalities in the infected host. Prior studies have shown that deletion of these genes does not alter DA levels in the brain or exploratory activity in infected mice. However, possible effects of AAH gene deficiency on infection-induced brain and behavior alterations that are directly linked to DA synaptic transmission have not been evaluated. We found that chronic T. gondii infection of BALB/c mice leads to blunted response to amphetamine or cocaine and decreased expression of Dopamine Transporter (DAT) and Vesicular Monoamine Transporter 2 (VMAT2). Deletion of AAH2 had no effects on these changes in infected mice. Both wild type and Δaah2 strains produced comparable levels of neuroinflammation. Our findings demonstrate that AAH2 is not required for T. gondii infection-produced DA-dependent neurobehavioral abnormalities.
Elsevier