Brainstem neuroadaptations in rodent models of Parkinson's disease

A classical theory of a key pathophysiological change in Parkinson's disease (PD) is that GABAergic neurons in the substantia nigra pars reticulata (SNr), an output structure of the basal ganglia, become hyperactive following the dopaminergic loss. Increased GABA release from the SNr neurons is thus likely to induce neuroadaptations in structures receiving a direct projection from the SNr, including the parabrachial nucleus (PBN), superior colliculus (SC), and periaqueductal gray (PAG). We have shown that the PBN indeed exhibits cellular and molecular changes in PD rat models. We thus expected the SC and the PAG to likewise show neuroplasticity. The objective of the present work was to evaluate the cellular and molecular plasticity in both the SC (lateral and medial) and the PAG in PD rats with a partial or total dopaminergic lesion. We used Golgi–Cox to measure the spine density and spine morphology and Western blot to analyze GABAA receptor expression in both PD rat models compared to sham animals. We found an increase in spine density (thin and stubby types) following total dopaminergic lesions in the SC and the PAG. Additionally, increased GABAA receptor expression was observed in the lateral SC in the total lesion group only. These results suggest compensatory mechanisms in PD that may delay disease onset and contribute to both motor and nonmotor symptoms. Further investigation should be performed to fully understand the functional impact of the plasticity revealed in this work.