Hypocretin (orexin) loss in Parkinson's disease

• Published in: Brain (London, England : 1878) England : 1878), 2007-06, Vol.130 (6), p.1577-1585
• Main Authors: Fronczek, Rolf, Overeem, Sebastiaan, Lee, Sandy Y. Y., Hegeman, Ingrid. M., van Pelt, Johannes, van Duinen, Sjoerd. G., Lammers, Gert Jan, Swaab, Dick F.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Cell Count; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Hypothalamus - chemistry; Hypothalamus - pathology; Immunoenzyme Techniques; Intracellular Signaling Peptides and Proteins - analysis; Intracellular Signaling Peptides and Proteins - cerebrospinal fluid; Intracellular Signaling Peptides and Proteins - deficiency; Lewy Bodies - chemistry; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Neurons - chemistry; Neuropeptides - analysis; Neuropeptides - cerebrospinal fluid; Neuropeptides - deficiency; Orexins; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Prefrontal Cortex - chemistry
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awm090

The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradictory results. In PD patients and matched controls, we (i) estimated the number of hypocretin neurons in post-mortem hypothalami using immunocytochemistry and an image analysis system (ii) quantified hypocretin levels in post-mortem ventricular CSF and (iii) prefrontal cortex using a radioimmunoassay. Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th-75th percentile). We showed a significant decrease between PD patients and controls in (i) the number of hypocretin neurons (PD: 20 276 (13 821-31 229); controls: 36 842 (32 546-50 938); P = 0.016); (ii) the hypocretin-1 concentration in post-mortem ventricular CSF (PD: 365.5 pg/ml (328.0-448.3); controls: 483.5 (433.5-512.3); P = 0.012) and (iii) the hypocretin-1 concentrations in prefrontal cortex (PD: 389.6 pg/g (249.2-652.2); controls: 676.6 (467.5-883.9); P = 0.043). Hypocretin neurotransmission is affected in PD. The hypocretin-1 concentration in the prefrontal cortex was almost 40% lower in PD patients, while ventricular CSF levels were almost 25% reduced. The total number of hypocretin neurons was almost half compared to controls.