Physiology and gene regulation of the brain NPY Y 1 receptor

Abstract

Neuropeptide Y (NPY) is one of the most prominent and abundant neuropeptides in the mammalian brain where it interacts with a family of G-protein coupled receptors, including the Y 1 receptor subtype (Y 1R). NPY-Y 1R signalling plays a prominent role in the regulation of several behavioural and physiological functions including feeding behaviour and energy balance, sexual hormone secretion, stress response, emotional behaviour, neuronal excitability and ethanol drinking. Y 1R expression is regulated by neuronal activity and peripheral hormones. The Y 1R gene has been isolated from rodents and humans and it contains multiple regulatory elements that may participate in the regulation of its expression. Y 1R expression in the hypothalamus is modulated by changes in energetic balance induced by a wide variety of conditions (fasting, pregnancy, hyperglycaemic challenge, hypophagia, diet induced obesity). Estrogens up-regulate responsiveness to NPY to stimulate preovulatory GnRH and gonadotropin surges by increasing Y 1R gene expression both in the hypothalamus and the pituitary. Y 1R expression is modulated by different kinds of brain insults, such as stress and seizure activity, and alteration in its expression may contribute to antidepressant action. Chronic modulation of GABA A receptor function by benzodiazepines or neuroactive steroids also affects Y 1R expression in the amygdala, suggesting that a functional interaction between the GABA A receptor and Y 1R mediated signalling may contribute to the regulation of emotional behaviour. In this paper, we review the state of the art concerning Y 1R function and gene expression, including our personal contribution to many of the subjects mentioned above.