Neuropeptide Y

Neuropeptide tyrosine (neuropeptide Y [NPY]) is widely expressed in the CNS and peripheral nervous systems and has been shown to have a role in numerous physiologic processes, including modulation of cortical excitability,¹ circadian rhythms,² stress response and emotion,^3,4 pain processing,^5–7 food intake,⁸ and cardiovascular function.⁹ NPY has been implicated in mechanisms of epilepsy,^1,10 anxiety and depression,^11,12 pain and analgesia,⁶ neuroprotection,¹³ and neurogenesis.¹⁴ This review focuses on selective aspects of NPY neurobiology and its relationship with CNS disorders.

DISTRIBUTION AND SYNAPTIC ACTIONS OF NPY IN THE CNS

NPY is a 36–amino acid member of the pancreatic polypeptide family that is widely distributed in the CNS, peripheral nervous system, and many other tissues. In the CNS, NPY is predominantly expressed in interneurons of the neocortex, hippocampus, striatum, and amygdala, particularly in those synthesizing γ-aminobutyric acid (GABA) and somatostatin.¹³ NPY is also present in long projections neurons, including brainstem catecholaminergic groups and neurons in the arcuate (infundibular) nucleus of the hypothalamus.^8,13 NPY, like other neuropeptides, is synthesized in the neuronal cell body, stored and transported in dense core vesicles by fast anterograde axonal transport, and released during high frequency neuronal activity, such as that observed during an epileptic seizure. NPY is a potent neuromodulator of neurotransmission^15,16 (figure).