title: Disturbed sleep/wake rhythms and neuronal cell loss in lateral hypothalamus and retina of mice with a spontaneous deletion in the ubiquitin carboxyl-terminal hydrolase L1 gene.
abstract: Many neurodegenerative disorders including Parkinson's disease (PD) and Alzheimer's disease (AD) are associated with sleep disturbances with presumably multifactorial etiology. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is involved in the pathophysiology of PD and AD. In the present study, we analyzed locomotor rhythms, orexin A-immunoreaction (Ir) in the lateral hypothalamus (LH) and melanopsin-Ir in the retina of gracile axonal dystrophy (gad) mice with a spontaneous deletion in the Uch-l1 gene. In constant darkness, gad mice showed circadian rhythms in locomotor activity, indicating the integrity of the endogenous circadian rhythm generator. However, gad mice showed an increased activity during subjective day and a decreased number of orexin A-immunoreactive neurons in the LH compared with the wild type (WT). In addition, gad mice showed increased locomotor activity in the light period when kept in a standard photoperiod and entrainment to phase shifts was significantly slower than in WT. Moreover, melanopsin-Ir was significantly reduced in the retina of gad mice, suggesting an impairment of circadian light perception in gad mice.
authors.affiliation: Dr. Senckenbergische Anatomie, Institute of Anatomy II, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Pfeffer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Plenzig
authors.forename: Suzana
authors.initials: S
authors.lastname: Gispert
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Horst-Werner
authors.initials: HW
authors.lastname: Korf
authors.forename: Charlotte
authors.initials: C
authors.lastname: Von Gall
mesh_terms: D000818:Animals; D001683:Biological Clocks; D021081:Chronobiology Disorders / Q000150:complications / Q000503:physiopathology*; D002940:Circadian Rhythm; D017353:Gene Deletion; D007031:Hypothalamus / Q000473:pathology / Q000503:physiopathology*; D055537:Light Signal Transduction; D008124:Locomotion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons; D012160:Retina / Q000473:pathology / Q000503:physiopathology*; D012893:Sleep Wake Disorders / Q000150:complications / Q000503:physiopathology*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse