Chemogenetics orexin/hypocretin intervention ameliorates Hipp-dependant memory imparment in A53T mice model of Parkinson's disease

Naol Kebede, Milos Stanojlovic, Jean Pierre Pallais, Catherine Kotz; University of Minnesota- Department of Integrative Biology & Physiology.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. PD has various
non-classical symptoms in addition to hallmark motor impairments, including cognitive
impairments. In addition, inflammation and astrogliosis are recognized as an integral part of PD
pathology. The hippocampus (Hipp) is a brain region involved in cognition and memory, and
the neuropeptide orexin has been shown to enhance learning and memory. Previous studies
show impairments in Hipp-dependent memory in a transgenic mouse model of PD (A53T mice)
and we hypothesized that increasing orexin tone will reverse this. The data show that early
cognitive impairment is coupled with an increase in expression of inflammatory and astrogliosis
markers. Mice were given intra-hippocampal injections of orexin or chemogenetic viral
injections of an orexin neuron specific Designer Receptor Exclusively Activated by Designer
Drug (DREADDs). Mice were either intracranially treated with orexin A or given clozapine N-
oxide (CNO) if transfected with DREADDs. Both pharmacological orexin intervention and
chemogenetic activation of orexin neurons ameliorated Hipp-dependent early memory
impairment observed in A53T mice. This study implicates orexin in PD-associated cognitive
impairment and suggests that exogenous orexin treatment and/or manipulation of endogenous
orexin levels may be a potential strategy for addressing early cognitive loss in PD.

Additional Abstract Information

Presenter: Naol Kebede

Institution: Hamline University

Type: Poster

Subject: Biology

Status: Approved

Time and Location

Session: Poster 3
Date/Time: Mon 4:30pm-5:30pm
Session Number: 3077