Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an α-synuclein based rat model for Parkinson’s disease
Posted on 2019-10-31 - 06:02
Abstract Aggregation of alpha-synuclein (α-SYN) is the pathological hallmark of several diseases named synucleinopathies, including Parkinson’s disease (PD), which is the most common neurodegenerative motor disorder. Alpha-SYN has been linked to synaptic function both in physiological and pathological conditions. However, the exact link between neuronal activity, α-SYN toxicity and disease progression in PD is not clear. In this study, we aimed to investigate the effect of chronic neuromodulation in an α-SYN-based rat model for PD using chemogenetics. To do this, we expressed excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) combined with mutant A53T α-SYN, using two different recombinant adeno-associated viral (rAAV) vectors (serotypes 2/7 and 2/8) in rat substantia nigra (SN) and investigated the effect on motor behavior, synapses and neuropathology. We found that chronic neuromodulation aggravates motor deficits induced by α-SYN, without altering dopaminergic neurodegeneration. In addition, neuronal activation led to changes in post-translational modification and subcellular localization of α-SYN, linking neuronal activity to the pathophysiological role of α-SYN in PD.
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Torre-Muruzabal, Teresa; Devoght, Jens; Van den Haute, Chris; Brône, Bert; Van der Perren, Anke; Baekelandt, Veerle (2019). Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an α-synuclein based rat model for Parkinson’s disease. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4708766.v2
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AUTHORS (6)
TT
Teresa Torre-Muruzabal
JD
Jens Devoght
CV
Chris Van den Haute
BB
Bert Brône
AV
Anke Van der Perren
VB
Veerle Baekelandt