Objective: Characterization of extra-striatal manifestations in the 6-hydroxydopamine (6-OHDA) Parkinson’s disease (PD) animal model.

Background: PD is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. This results in the onset of motor and non-motor manifestations. Non-motor symptoms, such as cognitive decline, psychiatric disturbances and sleep difficulties, are not well-investigated in established PD animal models. It is currently discussed whether these manifestations are affected by pathological changes of extra-striatal structures.

Methods: Intra-striatal lesions were induced by unilateral stereotactic injections of 6-OHDA in adult male mice. 3 weeks post-surgery lesion induction was verified by behavioural testing. Loss of tyrosine hydroxylase (TH) fibres plus microglia and astrocyte activation were quantified by means of design-based stereological approaches in nigro-striatal and extra-striatal regions.

Results: Successfully induced lesions revealed reduced TH-positive fibre density in the dorsal and central part of the striatum accompanied by a massive retrograde loss of TH-positive neurons in the substantia nigra. In contrast, the ventral tegmental area was only marginally affected. A substantial loss of TH-positive fibres was observed in the cortical cingulate and motor area. Furthermore, signs of microgliosis were evident within the striatum and thalamus but not in the examined cortical regions.

Conclusions: These results demonstrate that intra-striatal injections of 6-OHDA lead to pathological changes in extra-striatal structures including cingulate-, motor cortex and thalamus possibly influencing non-motor symptoms. Further studies can help to investigate underlying mechanisms contributing to functional sequelae in this PD animal model.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-intra-striatal-6-ohda-lesion-on-extra-striatal-structures-in-the-mouse/