(2017) Sleep/wake disorders and the hypocretin/orexin system in a zebrafish model of Parkinsons Disease.

ABSTRACT

Introduction: Sleep/wake alterations are non-motor symptoms present in various neurological disorders including Parkinson’s Disease (PD). Hypocretin/orexin, whose deficit is the main cause of narcolepsy, is involved in sleep/wake regulation. Since zebrafish is a suitable model for PD and sleep/wake behaviour, we evaluated the sleep/wake changes associated with alterations in the hypocretin (Hcrt) system in a PD zebrafish model. Material and methods: We challenged 2 dpf zebrafish larvae with 6-hidroxidopamine (6-OHDA) during 72 hours using WT and Tg(Hcrt:EGFP) lines. Dopaminergic and Hcrt neurones were examined and quantified by anti-tyrosine hydroxylase (TH), anti-GFP immunostaining and confocal imaging. TH neurons and Hcrt receptor were also observed by in situ hybridisation. Locomotor activity during day and night was measured with an automated tracking video system (TrackFish). Results: The number of expressing TH (protein and mRNA) and Hcrt neurons decreased after 6-OHDA. The diencephalic 5-6-11 groups of aminergic cells, which resemble the mammalian substantia nigra, were sensitive to 6-OHDA. We found defects in zebrafish locomotor activity, i.e. distance travelled and swimming speed and sleep/wake pattern. Locomotion, but not number of TH neurons, improved after two-day recovery following 6-OHDA. Discussion: Results suggest that 6-OHDA induces a behavioural disorder in zebrafish larvae. Alterations may arise from a reduced 5-6-11 dopaminergic population and/or be secondary to the reduced number and activity of Hcrt neurons. Funding: ICM P09-015-F, FONDECYT (3150540, 1161274, 1151029), CONICYT PIA ACT1402, FONDAP 15150012.

Izquierdo AL, Castañeda V, Härtel S, Concha M

Mechanisms Of Development (Mech Dev.)

julio 31, 2017

DOI: 10.1016/j.mod.2017.04.352

Investigador BNI: Steffen Härtel , Miguel Concha