Depletion of hypothalamic hypocretin/orexin neurons correlates with impaired memory in a Parkinson's disease animal model.

Parkinson's disease (PD) is a progressive and chronic neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and affects multiple neurotransmission systems such as hypocretin/orexin (HO) release and can lead to cognitive and memory deficits. The HO neurons located in lateral hypothalamus/perifornical area (LH/PeF) are involved with consolidation and memory processes. Here we verified the involvement of HO deficit in learning and memory process in an animal model of PD induced by bilateral intra-striatal injections of 6-hydroxydopamine (6-OHDA). The present study performed a working memory test by object recognition task and spatial memory test using the Morris water maze in control and PD-induced animals after depletion of HO neurons. In addition, our results indicate that HO system in degenerative disorders such as PD may modulate the declarative and spatial memory (assessed by object recognition and Morris water maze tests, respectively). A significant reduction of HO neurons in the LH/PeF and HO degeneration process in the hippocampus (CA1 and dentate gyrus areas) were noticed. Our data suggest that the HO system degeneration could be associated to memory dysfunction in PD. • PD animals present reduction of HO neurons. • HO inputs to CA1 and DG are degenerated in PD. • HO reduction correlates to impaired spatial and declarative memory in control and PD animals. [ABSTRACT FROM AUTHOR]