Melatonin treatment of repetitive behavioral deficits in the Cntnap2 mouse model of autism spectrum disorder.

Nighttime light pollution is linked to metabolic and cognitive dysfunction. Many patients with autism spectrum disorders (ASD) show disturbances in their sleep/wake cycle, and may be particularly vulnerable to the impact of circadian disruptors. In this study, we examined the impact of exposure to dim light at night (DLaN, 5 lx) in a model of ASD: the contactin associated protein-like 2 knock out (Cntnap2 KO) mice. DLaN was sufficient to disrupt locomotor activity rhythms, exacerbate the excessive grooming and diminish the social preference in Cntnap2 mutant mice. On a molecular level, DLaN altered the phase and amplitude of PER2:LUC rhythms in a tissue-specific manner in vitro. Daily treatment with melatonin reduced the excessive grooming of the mutant mice to wild-type levels and improved activity rhythms. Our findings suggest that common circadian disruptors such as light at night should be considered in the management of ASD.

Deletion of indoleamine 2,3 dioxygenase (Ido)1 but not Ido2 exacerbates disease symptoms of MOG35-55-induced experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with pathological features of inflammation, demyelination, and neurodegeneration. Several lines of evidence suggest that the enzymes indoleamine 2,3-dioxygenase (Ido)1 and/or Ido2 influences susceptibility to autoimmune diseases. Deletion of Ido1 exacerbates experimental autoimmune encephalomyelitis (EAE) an animal model of MS. However, no data exist on the role of Ido2 in the pathogenesis of EAE. We investigated whether deletion of Ido2 affected the pathogenesis of EAE. Temporal expression of interferon gamma (Ifng), Ido1 variants, Ido2 variants, as well as genes encoding enzymes of the kynurenine pathway in the spleen and spinal cord of C57BL/6 mice with or without EAE were determined by RT-qPCR. Moreover, EAE was induced in C57BL/6, two Ido1 knockout strains (Ido1KO and Ido1TK) and one Ido2 knockout mouse strain (Ido2-/-) and disease monitored by clinical scores and weight change. Performance on the rotarod was performed on days 0, 5, 10 and 15 post induction. The extent of demyelination in the spinal cord was determined after staining with Oil red O. The development of EAE altered gene expression in both the spleen and spinal cord. Deletion of Ido1 exacerbated the clinical symptoms of EAE. In stark contrast, EAE in Ido2-/- mice did not differ clinically or histologically from control mice. These results confirm a protective role for Ido1, on the pathogenesis of MOG35-55-induced EAE in C57BL/6J mice.