Neonatal 6‐OHDA lesion of the SNc induces striatal compensatory sprouting from surviving SNc dopaminergic neurons without VTA contribution

William Tanguay, Charles Ducrot, Nicolas Giguère, Marie‐Josée Bourque, Louis‐Eric Trudeau
Eur J Neurosci. 2021-09-20; 54(7): 6618-6632
DOI: 10.1111/ejn.15437

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Tanguay W(1), Ducrot C(1), Giguère N(1), Bourque MJ(1), Trudeau LE(1).

Author information:
(1)Department of Pharmacology and Physiology and Department of Neurosciences, Faculty of Medicine, Central Nervous System Research Group (GRSNC), Université de Montréal, Montreal, Quebec, Canada.

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) are uniquely
vulnerable to neurodegeneration in Parkinson’s disease (PD). We hypothesize that
their large axonal arbor is a key factor underlying their vulnerability, due to
increased bioenergetic, proteostatic and oxidative stress. In keeping with this
model, other DAergic populations with smaller axonal arbors are mostly spared
during the course of PD and are more resistant to experimental lesions in animal
models. Aiming to improve mouse PD models, we examined if neonatal partial SNc
lesions could lead to adult mice with fewer SNc DA neurons that are endowed with
larger axonal arbors because of compensatory mechanisms. We injected
6-hydroxydopamine (6-OHDA) unilaterally in the SNc at an early postnatal stage at
a dose selected to induce loss of approximately 50% of SNc DA neurons. We find
that at 10 and 90 days after the lesion, the axons of SNc DA neurons show massive
compensatory sprouting, as revealed by the proportionally smaller decrease in
tyrosine hydroxylase (TH) in the striatum compared with the loss of SNc DA neuron
cell bodies. The extent and origin of this axonal sprouting was further
investigated by AAV-mediated expression of eYFP in SNc or ventral tegmental area
(VTA) DA neurons of adult mice. Our results reveal that SNc DA neurons have the
capacity to substantially increase their axonal arbor size and suggest that mice
designed to have reduced numbers of SNc DA neurons could potentially be used to
develop better mouse models of PD, with elevated neuronal vulnerability.

© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

 

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