Theme 3 | Rare diseases

Altered dopaminergic and serotonergic cell populations in the dorsal raphe nucleus of a narcoleptic subject. 

Faisal Alosaimi

Faisal Alosaimi1,2,3, Yasin Temel1,2, Sylvana Pol1,2, Sarah Hecham1,2 and Ali Jahanshahi1,2

1 Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands
2 School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
3 Department of Physiology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia

Narcolepsy is a sleep disorder with a relatively unknown underlying neuropathological mechanism. Early studies suggests that degeneration of orexin expressing neurons in lateral hypothalamus (LH) might play a role. Recent research has revealed that dopaminergic neuronal activity in dorsal raphe nucleus (DRN) changes during sleep-wake cycle. In addition, the serotoninergic neurons in the DRN exert a critical role in regulating the sleep-wake- cycle. Interestingly, these two neurotransmitter systems modulate the activity of the LH orexinergic neuros during sleep-wake cycle. Based on these evidences, we hypothesized that the DRN dopaminergic and serotoninergic cell populations can be affected in narcolepsy subjects. 

We performed immunohistochemistry to investigate the dopaminergic and serotoninergic cell populations in the DRN of an individual with narcolepsy and age/sex matched control subject; using antibody against tyrosine hydroxylase (TH) and phenylalanine hydroxylase-8 (PH8), respectively. Nissl staining was also performed to assess cell density

Semi-quantitative analysis revealed reduced dopaminergic and serotonergic cell populations in the DRN of the narcoleptic subject when it was compared to the control. In addition, the cell density of dopaminergic and serotonergic was also reduced. Furthermore, The Nissl staining shown that the cell density is similar in both subjects

This semi-quantitative dataset demonstrates a reduced dopaminergic and serotoninergic cell populations in a narcoleptic subject. The reasons behind this could be either cell death or loss of function in the DRN neurons. This is a N=1 study as narcolepsy brain specimens is very hard to obtain. Yet, it worth reporting as this observation could highlights the importance and significance of the DRN serotonergic and dopaminergic neurons in the pathophysiology of narcolepsy in future studies.

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