Hypocretin (orexin) cell loss in Parkinson's disease

TLDR

Parkinson’s disease is accompanied by sleep attacks, insomnia, REM‑behavior disorder, hallucinations and depression—symptoms also seen in narcolepsy, which results from selective loss of hypocretin neurons. The study aimed to determine whether hypocretin neurons are damaged in Parkinson’s disease. Post‑mortem hypothalamic and substantia nigra tissues from 11 PD and 5 normal brains were immunostained for hypocretin‑1, MCH, alpha‑synuclein and GFAP, and stereological analyses quantified cell number, distribution and size while correlating the results with Hoehn‑Yahr stage and Braak neuropathology.

Abstract

It has recently been reported that Parkinson's disease (PD) is preceded and accompanied by daytime sleep attacks, nocturnal insomnia, REM sleep behaviour disorder, hallucinations and depression, symptoms which are frequently as troublesome as the motor symptoms of PD. All these symptoms are present in narcolepsy, which is linked to a selective loss of hypocretin (Hcrt) neurons. In this study, the Hcrt system was examined to determine if Hcrt cells are damaged in PD. The hypothalamus of 11 PD (mean age 79 ± 4) and 5 normal (mean age 77 ± 3) brains was examined. Sections were immunostained for Hcrt-1, melanin concentrating hormone (MCH) and alpha synuclein and glial fibrillary acidic protein (GFAP). The substantia nigra of 10 PD brains and 7 normal brains were used for a study of neuromelanin pigmented cell loss. The severity of PD was assessed using the Hoehn and Yahr scale and the level of neuropathology was assessed using the Braak staging criteria. Cell number, distribution and size were determined with stereologic techniques on a one in eight series.