Emotional memory impairments induced by AAV-mediated overexpression of human α-synuclein in dopaminergic neurons of the ventral tegmental area

Behavioural Brain Research
A AlvarssonP Svenningsson

Abstract

Parkinson's disease (PD) is associated with extensive degeneration of dopaminergic neurons originating in the substantia nigra pars compacta, but neuronal loss is also found in the ventral tegmental area (VTA). The VTA projects to areas involved in cognitive and emotional processes, including hippocampus, amygdala, nucleus accumbens and prefrontal cortex, and has thus been proposed to play a role in emotional memory impairments in PD. Since the formation of α-synuclein inclusions throughout the central nervous system is a pathological hallmark of PD, we studied the progressive effects of α-synuclein overexpression in the VTA on motor functions, emotional behaviour and emotional memory. Adeno-associated viral (AAV) vectors encoding either human α-synuclein or green fluorescent protein (GFP) were injected stereotactically into the VTA, and behaviour was monitored 3 and 8 weeks following AAV injection. At week 8, there was a 22% reduction of TH+ neurons in the VTA. We demonstrate that α-synuclein overexpression in dopaminergic neurons of the VTA induced mild motor deficits that appeared 3 weeks following AAV-α-synuclein injection and were aggravated at week 8. No depressive- or anxiety-like behaviours were found. To address emotio...Continue Reading

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Citations

Apr 6, 2016·Neurobiology of Learning and Memory·Mayara AnselmiGeison Souza Izídio
Feb 9, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Rose B Creed, Matthew S Goldberg
Feb 26, 2019·Frontiers in Molecular Neuroscience·Christelle LasbleizJean-Michel Verdier
Jul 17, 2020·Behavioural Brain Research·Karenine M H CavalcanteJosé R Santos
Mar 30, 2021·Brain, Behavior, and Immunity·Tingfu DuKaili Ma

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