Parkinson's disease (PD) is a neurodegenerative disorder characterized by resting tremor, rigidity, bradykinesia and a plethora of non-motor manifestations. In particular, the onset of motor symptoms is often preceded by mild cognitive impairment, which can progress to overt dementia. Neuroinflammation has recently emerged as one of the key processes involved in the pathogenesis of PD. Indeed, markers of inflammation were found in the brains of PD mouse models.In the present work, we evaluated the expression of inflammatory markers at 2 and 6 months of age in the striatum and hippocampus of two different models of PD: PTEN-induced kinase1 knock-out (PINK1-/-) mice, a model of monogenic PD, and mice overexpressing human wild-type alpha-synuclein (ASYN, line 61), a model of sporadic PD. The levels of pro-BDNF, BDNF, TrkB, IL-1, IL-6 and IL-18, and the microglia marker IBA-1, were evaluated with ELISA and WB. In the mutant mice, we found increased levels of IL-6, IL-1 and IBA-1 in the striatum, but not in the hippocampus, where the TrkB/BDNF pathway was altered. We then investigated the ability of two types of environmental enrichment, one specifically cognitive (CE) and the other multimodal (EE, including both cognitive and motor stimulation), to revert neuroinflammation. Interestingly, CE and EE showed a similar effectiveness to revert these molecular alterations, since both were able to blunt striatal neuroinflammation.Overall, these observations provide a molecular basis for the effects of cognitive and multimodal stimulation as non-pharmacological add-on interventions in PD.