A role of NELL2 in homeostatic regulation of mammals

Abstract

We have previously found that NELL2, a mammalian neural tissue-specific epidermal growth factor-like repeat domain-containing protein, is a downstream protein of estrogen. Several studies have reported broad distribution of NELL2 mRNA and protein in embryonic and postembryonic , but its highest expression was observed-in neural tissues. Thus, NELL2 has been suggested to play a role in neuronal proliferation, differentiation, synaptic formation, and survival during development and postnatal life. We have been studying potential NELL2 function in rat brain using anatomical and histochemical approach in vivo. In the hypothalamus, content of NELL2 was high in the ventromedial hypothalamic nucleus, supraoptic nucleus and paraventricular nucleus in contrast with moderate-to-low expression in most other areas including arcuate nucleus (ARC) and sexually dimorphic nucleus of the preoptic area (SDN-POA). Furthermore, NELL2 was expressed in the proopiomelanocortin and neuropeptyde Y expressing cells in the ARC. By these results, we hypothesized that NELL2 might be involved in certain animal behaviors like food intake and sexual behavior. Using antisense NELL2 oligomer, we effectively down-regulated expression of NELL2 in the hypothalamus and manipulated feeding behavior as well as male sexual behavior. Blockade of NELL2 reduced food intake resulting in loss of body weight. Interestingly, it also influenced on certain male sexual behavior such as mounting and intromit by changing volume of the SDN-POA. Our data suggest that NELL2 is involved in various rodent brain physiology.