Alterazioni indotte da stress di bio-marcatori delle vie ascendenti uditive in topi BLEV

Corticosterone is a steroid hormone involved in stress response in rodents. It is secreted by the adrenal gland through a circadian rhythm, presenting the higher concentration at the beginning of the nighttime. In this thesis, corticosterone concentrations in BDNF-live-exon-viewing (BLEV) mice were increased by oral and intraperitoneal corticosterone treatments. The strain of BLEV mice, first generated by the group of Prof. Marlies Knipper in the ENT-clinic in Tuebingen, possesses BDNF exons IV and VI labelled respectively with a cyan and yellow fluorescent protein that allow to study BDNF plasticity-related transcription in vivo. Corticosterone levels, after oral and intraperitoneal treatments, were assessed in mice biological fluids using ELISA technique. Concerning the oral treatment, corticosterone concentrations were analysed in urine immediately, three and six hours after the treatment. Regarding the intraperitoneal treatment, mice were divided in different groups to receive one or three injections of corticosterone, in order to investigate the effects of acute (one injection) and sub-chronic (three injections) stress in biological fluids as well as in the cochlea and hippocampus. Corticosterone levels were quantified in both urine and plasma immediately, two and five hours after treatment. The cochlea and the hippocampus of BLEV mice injected with corticosterone were examined at a confocal microscope, revealing alterations in the form and number of ribbon synapses and afferent fibres of the inner hair cells (IHCs) of the cochlea and in the expression of BDNF exon VI in CA3 region of the hippocampus. Although not quantified, the number of ribbon synapses and afferent fibres of the IHCs in the cochlea are increased in animals injected once (acute treatment) by approximately 50%, while they decreased in animals injected three times (sub-chronic treatment). In the hippocampus, corticosterone increased the expression of BDNF exon VI in all mice injected by 30% to 80%. These findings underline for the first time how corticosterone can influence differently sensory and cognitive brain areas in BLEV mice, as well as biological fluids.