Environmental enrichment ameliorates the impairments of a rodent model of prodromal Parkinson’s disease

: Parkinson's disease (PD) pathogenesis is multifactorial and involves both genetic and environmental factors, converging to induce mitochondrial and synaptic dysfunction, oxidative stress, and neuroinflammation. Although the disease is characterized by cardinal motor symptoms (bradykinesia, rigidity, and/or resting tremor), in a majority of PD patients non-motor symptoms, including disorders of mood and affect, sensory and autonomic dysfunction, pain, disturbances of the sleep-wake cycle and cognitive impairment, anticipate the onset of motor symptoms and aggravate the burden of symptomatology along disease progression. Recent clinical observations suggest that non-pharmacological interventions, such as cognitive and physical training, may exert a beneficial effect on motor and non-motor PD symptoms. Herein, we aimed at investigating the effects of either cognitive or multimodal stimulation on the neurobiological and behavioral alterations of a PD mouse model. Cognitive and multimodal stimulation were provided in the form of environmental enrichment to 2-month-old mice with deletion of PD-associated PTEN-induced putative kinase 1 gene (PINK1-/- mice). Overall, our data support young PINK1-/- mice as a valuable experimental model of preclinical PD, mimicking the behavioral disturbances and providing hints on the neurobiological mechanisms of the disease. Furthermore, the present study shows that multimodal environmental enrichment, a non-pharmacological treatment providing prolonged sensory, motor, and cognitive stimulation, is able to revert both the behavioral and neurobiological alterations of the PD mouse model. These data provide experimental support to growing clinical evidence of benefits deriving from cognitive and motor stimulation of PD patients, and identify the neurobiological targets of such non-pharmacological approaches.