CHAPTER J2 – Double-Lesion Animal Models of Multiple System Atrophy

Multiple system atrophy is a neurodegenerative disease of undetermined etiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar, and pyramidal signs. There is at present no effective therapy to reverse this condition. Levodopa-unresponsive parkinsonism dominates the clinical syndrome of multiple system atrophy of the striatonigral degeneration subtype, a condition that is characterized by a dual pathology affecting nigral dopaminergic neurons and their striatal output neurons. Experimental models reproducing salient pathological and clinical features are needed to better understand the underlying pathophysiology of parkinsonian motor signs and levodopa-unresponsiveness. This chapter illustrates the feasibility of such models in rodents and in non-human primates. In rodents, the combined striatal and nigral lesions that are different from those induced by a single striatal or nigral lesion induce complex motor symptoms. These models are helpful in understanding the degenerative process in multiple system atrophy and in exploring new therapeutic strategies prior to clinical applications in humans. These novel MSA models may shed light on the poorly understood interaction between glial and neuronal dysfunction.