Kalinichenko, Liubov S. and Kohl, Zacharias and Muehle, Christiane and Hassan, Zurina and Hahn, Agnes and Schmitt, Eva-Maria and Macht, Kilian and Stoyanov, Lyubomir and Moghaddami, Schayan and Bilbao, Roberto and Eulenburg, Volker and Winkler, Juergen and Kornhuber, Johannes and Mueller, Christian 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, 168 (3). pp. 269-287. ISSN 0022-3042, 1471-4159
Full text not available from this repository. (Request a copy)Abstract
Point mutations in the alpha-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 alpha-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMPAIRED HIPPOCAMPAL NEUROGENESIS; PARKINSONS-DISEASE; ACID SPHINGOMYELINASE; SEROTONERGIC DYSFUNCTION; NONMOTOR SYMPTOMS; RISK; DISORDERS; SYSTEM; MODEL; MOTOR; A53T; alcohol; ceramide; depression; neutral sphingomyelinase; Parkinson's disorder |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Jan 2026 06:59 |
| Last Modified: | 16 Jan 2026 06:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65170 |
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