Regulation of neuropeptide Y mRNA and peptide concentrations by copper in rat olfactory bulb

Neuropeptide Y is highly abundant in both the peripheral and central nervou s systems and is known to have diverse functions including regulation of fe eding behavior, blood pressure, circadian rhythms, reproductive behavior an d the response to stress. Northern analysis showed that copper deficiency i ncreased brain NPY mRNA abundance particularly in the olfactory bulb (OB). These increases were not accompanied by alterations in food intake or blood pressure. After 4 weeks of a copper-restricted diet, OB copper concentrati ons decreased to 44% of control and NPY mRNA increased 1.5-fold. Addition o f a copper chelator to the restricted diet, resulted in a two-fold increase in OB NPY mRNA over copper adequate controls. These results were confirmed in primary cultures of OB neurons suggesting that the regulation of NPY mR NA is at the level of the bulb rather than by a hormonal or other copper-re gulated factor external to the OB. Immunoreactive NPY (IR-NPY) levels were not, however, increased following the 4 weeks of copper deficiency. Additio n or the chelator resulted in a 1.4-fold increase in IR-NPY that, while sta tistically significant, was not proportional to the two-fold increase in NP Y mRNA in the same study. This may suggest that copper deficiency inhibits the translational mechanisms responsible for the synthesis of NPY or that N PY is exported From the bulb in copper deficiency. (C) 1999 Elsevier Scienc e B.V. All rights reserved.