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

Ross McFarland, Zi Teng Wang, Yan Jouroukhin, Ye Li, Olga Mychko, Isabelle Coppens, Jian-Chun Xiao, Lorraine V Brando, Robert H Yolken, L. David Sibley, Mikhail Pletnikov

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)193-200
Number of pages8
JournalBehavioural Brain Research
Volume347
DOIs
StatePublished - Jul 16 2018

Fingerprint

Toxoplasma
Dopamine
Toxoplasmosis
Infection
Genes
Synaptic Transmission
Vesicular Monoamine Transport Proteins
Protozoan Infections
Aromatic Amino Acids
Dopamine Plasma Membrane Transport Proteins
Gene Deletion
Brain
Amphetamine
Mixed Function Oxygenases
Cocaine
Psychiatry
Parasites
Genome
Enzymes
Proteins

Keywords

  • AAH2
  • Amphetamine
  • Cocaine
  • DAT
  • Dopamine
  • Toxoplasma

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

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title = "AAH2 gene is not required for dopamine-dependent neurochemical and behavioral abnormalities produced by Toxoplasma infection in mouse",
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.",
keywords = "AAH2, Amphetamine, Cocaine, DAT, Dopamine, Toxoplasma",
author = "Ross McFarland and Wang, {Zi Teng} and Yan Jouroukhin and Ye Li and Olga Mychko and Isabelle Coppens and Jian-Chun Xiao and Brando, {Lorraine V} and Yolken, {Robert H} and Sibley, {L. David} and Mikhail Pletnikov",
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T1 - AAH2 gene is not required for dopamine-dependent neurochemical and behavioral abnormalities produced by Toxoplasma infection in mouse

AU - McFarland, Ross

AU - Wang, Zi Teng

AU - Jouroukhin, Yan

AU - Li, Ye

AU - Mychko, Olga

AU - Coppens, Isabelle

AU - Xiao, Jian-Chun

AU - Brando, Lorraine V

AU - Yolken, Robert H

AU - Sibley, L. David

AU - Pletnikov, Mikhail

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