Morphological and functional effects of a pro-resolving mediator in an α-synuclein rat model of Parkinson’s disease
Authors:
Francesca Cossa (1,2), Mariangela Massaro Cenere (1,2), Beatrice Zarrilli (1,2), Cecilia Giacomet (1,2), Mauro Federici (1), Vladimiro Batocchi (3), Ada Ledonne (1,2), Ezia Guatteo (1,4), Nicola Berretta (1), Valerio Chiurchiù (3,5), Nicola Biagio Mercuri (1,2)
Organisations:
1: Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
2: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
3: Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome, Italy
4: Department of Motor Science and Wellness, Parthenope University, Naples, Italy
5: Institute of Translational Pharmacology, CNR, Rome, Italy
Presenting author:
Francesca Cossa
Exposition date:
Saturday, September 16, 2023
Exposition position:
116/2
Accumulation of α-synuclein (α-syn) in Lewy bodies and Lewy neurites is one of the main pathological signatures of Parkinson’s disease (PD).
We have previously characterized the progressive functional and morphological neuronal alterations in a transgenic PD rodent model overexpressing the full-length human α-synuclein (SNCA+/+) compared to wild-type (WT) rats, at 4 and 12-13 months of age. Altered physiological properties of substantia nigra pars compacta (SNpc) dopamine (DA) neurons and neuroinflammation were observed in this rodent model. In particular, in the aged animals, the number of SNpc DA neurons was reduced, and the cells displayed hyperexcitability in response to depolarizing stimuli.
To test whether these changes were associated with a neuroinflammatory condition, we investigated morphological and electrophysiological features in the same model chronically treated (twice a week for ten months) with Resolvin D1 (RvD1), a pro-resolving molecule for inflammation.
RvD1 prevented SNpc TH-positive neuronal loss and increased soma size in 12-13 month-old SNCA+/+ rats.
These findings prompted us to investigate the electrophysiological properties of DA neurons.
In all experimental groups, only a few spontaneously firing cells were detected by multielectrode array (MEA) recordings in the SNpc, possibly because of the old age of the animals. No evident difference in basal firing was observed among the experimental groups.
In patch-clamp recordings, although we did not observe any differences in Ih current and passive membrane properties, the neuronal hyperexcitability was reduced in the RvD1-treated SNCA+/+ rats compared to the vehicle-treated ones.
In conclusion, RvD1 chronic treatment attenuated functional and morphological alterations in 12-13 month-old SNCA+/+ rats.
