title: Increased number of orexin/hypocretin neurons with high and prolonged external stress-induced depression.
abstract: It has been found that dysregulation in the orexin/hypocretin (Ox/HCRT) neuropeptide system in the lateral hypothalamus (LHA) is known to affect sleep disorder, depression and motor activities. However, to date there is no common agreement regarding the resulting specific changes induced in the Ox system. In this study, we inject corticosterone to produce stress-induced depressed mice and investigate the Ox neuronal and corresponding behavioural changes. Different doses (10, 20, 50mg/kgbw) of corticosterone were injected in adult mice, and then were tested in the open field test, forced swim test, tail suspension test, elevated plus maze test and motor activity measurements to validate the depressed animal model. Significant dose-dependent behavioural changes were observed in correlation with the doses of corticosterone. The effect is most significant and robust in the high 50mg/kgbw dose group five weeks after injection. Interestingly, we found on average a reduction in motor activity during the 12-hour dark phase (awake) of the depressed mice and no significant change during the light phase (asleep). Finally, using confocal microscopy, immunofluorescence (IF) analysis shows a significant increase (∼20%) in the number of Ox neurons in the LHA of the depressed mice as compared to the age-matched controls. This study suggests that an increase in Ox neuronal signaling may be functionally linked to high and prolonged external stress-induced depression.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom. Electronic address: j.jalewa@lancaster.ac.uk.
authors.forename: Jaishree
authors.initials: J
authors.lastname: Jalewa
authors.affiliation: Intelligent Systems Research Centre, University of Ulster, Magee Campus, Derry BT48 7JL, Northern Ireland, United Kingdom. Electronic address: k.wong-lin@ulster.ac.uk.
authors.forename: KongFatt
authors.initials: K
authors.lastname: Wong-Lin
authors.affiliation: Intelligent Systems Research Centre, University of Ulster, Magee Campus, Derry BT48 7JL, Northern Ireland, United Kingdom. Electronic address: tm.mcginnity@ulster.ac.uk.
authors.forename: T Martin
authors.initials: TM
authors.lastname: McGinnity
authors.affiliation: Intelligent Systems Research Centre, University of Ulster, Magee Campus, Derry BT48 7JL, Northern Ireland, United Kingdom. Electronic address: g.prasad@ulster.ac.uk.
authors.forename: Girijesh
authors.initials: G
authors.lastname: Prasad
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom. Electronic address: c.holscher@lancaster.ac.uk.
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D000818:Animals; D001835:Body Weight; D002452:Cell Count; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone; D003866:Depressive Disorder / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D007026:Hypothalamic Area, Lateral / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D009483:Neuropsychological Tests; D000068797:Orexins; D011897:Random Allocation; D013312:Stress, Physiological
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D003345:Corticosterone
keywords: Corticosterone; Depression; Motor activity; Orexin