MPTP-induced dopaminergic degeneration and deficits in object recognition in rats are accompanied by neuroinflammation in the hippocampus

Emotional changes, impairment of object recognition, and neuroinflammation are seen in Parkinson's disease with dementia (PDD). Here, we show that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the rat substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, microglial activation in the SNc and hippocampus, and cell loss in the hippocampal CA1 area. With regard to behavior, an increase in anxiety-like behavior and impairment of object recognition were observed during the fourth week after MPTP lesioning. The behavioral changes were not caused by motor impairment, since the rats had already recovered from MPTP-induced catalepsy before the tests were performed. These findings show that MPTP-induced neuroinflammation and its consequences, for example, microglial activation and cell loss in the hippocampus, may be involved in dopaminergic degeneration-related behavioral deficits and suggest that, in addition to the dopaminergic system, the limbic system may also participate in the pathophysiology of PDD. MPTP-lesioned rats are therefore proposed as a useful tool for assessing the ability of pharmacological agents to prevent recognition deficits in PDD.