We study physiological regulation in relation to the different phases of the wake-sleep cycle in genetically modified mice models of human pathologies. We evaluate the association between gene mutation and variations in cardiovascular, respiratory and thermoregulatory control. The characterization of the phenotypic profile also allows to monitor the effect of specific drug therapies. The genetically modified animals currently under study are: 1) Hcrt-KO mice (KO for the pre-pro-hypocretin/orexin gene) and Hcrt-ATX3-Tg mice (transgenic, which express the neurotoxin ataxin-3 in hypocretinergic neurons); these animals are models of narcolepsy. An experimental drug therapy is being tested in this model; 2) Ts65Dn mice, with partial trisomy of chromosome 16, models of Down syndrome (DS). These animals constitute a mouse model for the study of obstructive sleep apnea (common in DS patients) and for the study of Alzheimer's disease. We are evaluating the effect of sleep disturbances on the progression of neurodegeneration. Moreover, we carry out studies aimed at evaluating the animal's reactivity to stress and evaluate its effects on sleep.
The activity carried out at the CRBA mainly concerns PCR for the genetic characterization of animals generated from murine colonies, and RT-qPCR on brain tissue samples to evaluate the stress-dependent expression of glucocorticoid receptors; we also culture neurons on which we evaluate, by measuring intracytoplasmic calcium, the effect of experimental drugs for the treatment of narcolepsy which will subsequently be tested in vivo in narcoleptic mice.
Physiological regulation during sleep in genetically modified mice models of human pathologies