Neuropeptide Y (NPY) is a potent neurotransmitter that counteracts the behavioral and neuroendocrine effects of anxiety through the activation of Y1 receptor in the CNS. Experimental acute stress models, such as restraint stress, modulates NPY levels in the amygdala decreasing its mRNA, while repeated exposure to the same stress increases it. Moreover NPY is coupled with GABA in some brain area and together can act as an endogenous anxiolitic system to inhibit the excitatory effect of Corticotropin Releasing Factor (CRF) in the amygdala. By using a transgenic mouse model bearing the reporter gene beta-galactosidase (LacZ) coupled to the Y1 receptor promoter, we previously demonstrated that an increase in the brain concentration of neurosteroids induces a parallel increase in the Y1 expression in the amygdala. We now studied the effects of restraint, social isolation and footshock stress on the expression of the Y1R/LacZ transgene in the amygdala and in the Paraventricular nucleus (PVN) of Y1R/LacZ mice. Transgene expression significantly increases following single restraint exposure 6 hours post-stress in the central and medial amygdala and in the PVN. The cerebrocortical concentration of allopregnanolone and allotetrahydrodeoxycorticosterone also increases immediately after the stress and return to basal levels 30 minutes later. The administration of finasteride, a 5-alpha-reductase inhibitor, blocked this increase, but did not alter the Y1R/LacZ expression. Following ten day exposure to the restraint we still observed an augmentation in the brain neurosteroids levels but the transgene expression remains unchanged. Preliminary data from footshock experiment showed no variation in the Y1 gene expression suggesting that the NPY/Y1 neurotransmission depends on the duration and kind of stress input, while the social isolation, a long term anxiety/depression experimental model, showed a decrease in the cortical neurosteroids concentration and a parallel trend for the transgene expression in the amygdala. In conclusion we demonstrated that the Y1 receptor is up-regulated following acute restraint and that this modulation is independent on neuroactives steroids. Moreover a prolonged stress period resulted in a behavioral and neuroendocrine adaptation and the NPY system is differently regulated depending on the duration and the type of stress stimulus.
Restraint stress increases NPY Y1 receptor gene expression in the amigdala of Y1R-LacZ transgenic mice
MELE, PAOLO;EVA, Carola Eugenia;
2004-01-01
Abstract
Neuropeptide Y (NPY) is a potent neurotransmitter that counteracts the behavioral and neuroendocrine effects of anxiety through the activation of Y1 receptor in the CNS. Experimental acute stress models, such as restraint stress, modulates NPY levels in the amygdala decreasing its mRNA, while repeated exposure to the same stress increases it. Moreover NPY is coupled with GABA in some brain area and together can act as an endogenous anxiolitic system to inhibit the excitatory effect of Corticotropin Releasing Factor (CRF) in the amygdala. By using a transgenic mouse model bearing the reporter gene beta-galactosidase (LacZ) coupled to the Y1 receptor promoter, we previously demonstrated that an increase in the brain concentration of neurosteroids induces a parallel increase in the Y1 expression in the amygdala. We now studied the effects of restraint, social isolation and footshock stress on the expression of the Y1R/LacZ transgene in the amygdala and in the Paraventricular nucleus (PVN) of Y1R/LacZ mice. Transgene expression significantly increases following single restraint exposure 6 hours post-stress in the central and medial amygdala and in the PVN. The cerebrocortical concentration of allopregnanolone and allotetrahydrodeoxycorticosterone also increases immediately after the stress and return to basal levels 30 minutes later. The administration of finasteride, a 5-alpha-reductase inhibitor, blocked this increase, but did not alter the Y1R/LacZ expression. Following ten day exposure to the restraint we still observed an augmentation in the brain neurosteroids levels but the transgene expression remains unchanged. Preliminary data from footshock experiment showed no variation in the Y1 gene expression suggesting that the NPY/Y1 neurotransmission depends on the duration and kind of stress input, while the social isolation, a long term anxiety/depression experimental model, showed a decrease in the cortical neurosteroids concentration and a parallel trend for the transgene expression in the amygdala. In conclusion we demonstrated that the Y1 receptor is up-regulated following acute restraint and that this modulation is independent on neuroactives steroids. Moreover a prolonged stress period resulted in a behavioral and neuroendocrine adaptation and the NPY system is differently regulated depending on the duration and the type of stress stimulus.
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