Sex-specific pleiotropic changes in emotional behavior and alcohol consumption in human α-synuclein A53T transgenic mice during early adulthood

Kalinichenko L, Kohl Z, Mühle C, Hassan Z, Hahn A, Schmitt EM, Macht K, Stoyanov L, Moghaddami-Fara S, Bilbao Canalejas R, Eulenburg V, Winkler J, Kornhuber J, Müller CP (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Journal of neurochemistry

DOI: 10.1111/jnc.16051

Abstract

Point mutations in the α-synuclein coding gene may lead to the development of Parkinson's disease (PD). PD is often accompanied by other psychiatric conditions, such as anxiety, depression, and drug use disorders, which typically emerge in adulthood. Some of these point mutations, such as SNCA and A30T, have been linked to behavioral effects that are not commonly associated with PD, especially regarding alcohol consumption patterns. In this study, we investigated whether the familial PD point mutation A53T is associated with changes in alcohol consumption behavior and emotional states at ages not yet characterized by α-synuclein accumulation. The affective and alcohol-drinking phenotypes remained unaltered in female PDGF-hA53T-synuclein-transgenic (A53T) mice during both early and late adulthood. Brain region-specific activation of ceramide-producing enzymes, acid sphingomyelinase (ASM), and neutral sphingomyelinase (NSM), known for their neuroprotective properties, was observed during early adulthood but not in late adulthood. In males, the A53T mutation was linked to a reduction in alcohol consumption in both early and late adulthood. However, male A53T mice displayed increased anxiety- and depression-like behaviors during both early and late adulthood. Enhanced ASM activity in the dorsal mesencephalon and ventral hippocampus may potentially contribute to these adverse behavioral effects of the mutation in males during late adulthood. In summary, the A53T gene mutation was associated with diverse changes in emotional states and alcohol consumption behavior long before the onset of PD, and these effects varied by sex. These alterations in behavior may be linked to changes in brain ceramide metabolism.

Authors with CRIS profile

Liubov Kalinichenko Department of Psychiatry and Psychotherapy Zacharias Kohl Department of Molecular Neurology Christiane Mühle Department of Psychiatry and Psychotherapy Agnes Hahn Professur für Suchtmedizin Kilian Macht Professur für Suchtmedizin Lyubomir Stoyanov Professur für Suchtmedizin Schayan Moghaddami-Fara Professur für Suchtmedizin Roberto Bilbao Canalejas Department of Psychiatry and Psychotherapy Jürgen Winkler Professur für Molekulare Neurologie Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie Peter Christian Müller Professur für Suchtmedizin

Involved external institutions

Universität Leipzig DE Germany (DE) University of Science Malaysia (USM) / Universiti Sains Malaysia MY Malaysia (MY)

How to cite

APA:

Kalinichenko, L., Kohl, Z., Mühle, C., Hassan, Z., Hahn, A., Schmitt, E.M.,... Müller, C.P. (2024). Sex-specific pleiotropic changes in emotional behavior and alcohol consumption in human α-synuclein A53T transgenic mice during early adulthood. Journal of neurochemistry. https://doi.org/10.1111/jnc.16051

MLA:

Kalinichenko, Liubov, et al. "Sex-specific pleiotropic changes in emotional behavior and alcohol consumption in human α-synuclein A53T transgenic mice during early adulthood." Journal of neurochemistry (2024).

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