Cognitive and anxiety-like impairments accompanied by serotonergic ultrastructural and immunohistochemical alterations in early stages of parkinsonism.

Parkinson's disease (PD) is mostly known as a dopamine deficiency syndrome due the structural and functional changes in striatal projection neurons. However, studies have considered this pathology as a multi-systemic disease in which the neurodegenerative process extends beyond the dopaminergic system. Therefore, the purpose of the present study was to investigate the morphological and immunohistochemical changes associated with behavioral and cognitive alterations in a model of parkinsonism induced by low dose of reserpine. Animals showed anxiety-like behavior and deficits in short-term recognition memory. Besides, Tyrosine Hydroxylase (TH) immunoreactive cells decreased in reserpine (RES) group in CA1 and serotonin (5-HT) immunoreactive cells decreased in RES group in CA1, CA3 and medial prefrontal cortex (mPFC). Moreover, an increase in the area (μm2) of 5 H T labeled ultrastructure (axon terminal) was observed in RES group only in CA1 and mPFC. The evidence of alterations in 5-HT immunoreactive in the premotor phase of model of parkinsonism highlights the importance of looking beyond the nigrostriatal system to elucidate the underling mechanisms and deficits in other neurotransmitters systems. This provides vital information regarding novel interventions for the management of non-motor symptoms. Additionally, the low-dose reserpine treatment has an early effect on axonal ultrastructure. As the axonopathy in PD has been increasingly recognized, the focus on axonal neurobiology is noteworthy for both neuroprotective and restorative therapeutics, and the progressive reserpine rat model can be a useful tool in this search.