| Summary: | Parkinson’s disease can be caused by A53T or A30P mutations in the α-synuclein (SNCA) gene, or by multiplication of the gene locus. Patients often experience depression and anxiety. We investigated affect, serotonin content and bioenergetic homeostasis of mice expressing human wild-type (WT), A53T, A30P or A53T+A30P (DM) SNCA transgenes. A30P-Tg mice displayed altered affect, increased serotonin turnover and reduced ATP and complex I+III activity. To determine whether murine α-synuclein (Snca) might mask effects SNCA transgenes we re-examined effects of SNCA transgenes in Snca-/- mice. SNCA transgenes rescued anxiety, serotonin levels and ATP content in Snca-/- mice. Only A53T SNCA abrogated behavioural despair associated with decreased norepinephrine in Snca-/- brains. The A53T residue is the natural sequence of murine Snca, and appears to be important for synuclein function in mice. The Snca-/- mouse provides a means to study the effects of SNCA mutants, and the physiologic roles of Snca in vivo.
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