Characterization of the nigrostriatal pathway in Parkinson's Disease mice models of overexpression of human alpha-synuclein and LRRK2 mutants

Parkinson's disease (PD) is a long-term neurodegenerative disease with a complex array of symptoms and signs, involving general symptoms such as pain and fatigue, but mostly characterised by loss of motor coordination and late-stage psychological disorders such as psychosis and dementia. Other key signs of PD are loss of dopamine and neuronal death in the nigrostriatal pathway, most notably dopaminergic neurons of the substantia nigra pars compacta, found on the ventrolateral side of the midbrain, leading to loss of dopaminergic input in the caudate and putamen of the basal ganglia (also called striatum); and the appearance of Lewy bodies and Lewy neurites, the previous being alpha-synuclein in the soma of neurons and the latter in cell processes. To date, PD is the second most prevalent neurodegenerative disease after Alzheimer’s disease. It has been reported to have a prevalence of 1-2 people out of 1000 at all times in unselected populations, affecting 1% of people over the age of 60 worldwide. This number of affected people is growing, and certain authors, experts in the topic of PD, estimate that the number of people affected by PD will exceed 12 million worldwide by 2040. Several strategies have been studied to attempt to stop the neurodegenerative process and increase the quality of life of PD patients, yet unfortunately so far no cure or therapy has been found for this disease. It is important to then continue to research PD, and this requires models to assess novel therapeutical approaches. In this thesis, we study two different mice PD models: C57BL/6J-Tg(Th-SNCA*A30P*A53T)39Eric/J and C57BL/6J-Tg(LRRK2*G2019S)2AMjff/J, and we use different strategies to improve the models for future preclinical data for therapeutic studies. We were able to find that our C57BL/6J-Tg(Th-SNCA*A30P*A53T)39Eric/J mice presented higher content in striatal dopamine, reactive microgliosis in the nigrostriatal pathway and motor dysfunctions with hypoactivity. When challenged with