Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Osteocalcin Gene Relationship in Energy Regulation, Bone Homeostasis and Reproductive Organs Analyzed by mRNA Quantitative Evaluation and Linear Correlation Analysis

Abstract

Nerve Growth Factor (NGF)/Brain-derived Neurotrophic Factor (BDNF) and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF, and Osteocalcin we compared by RT-PCR the transcript levels of <i>Ngf, Bdnf</i> and <i>Osteocalcin</i> as well as of their receptors <i>p75NTR/NTRK1, NTRK2</i>, and <i>Gprc6a</i> in brain, bone, white/brown adipose tissue (WAT/BAT) and reproductive organs of 3 months old female and male mice. Brain and bone were used as positive controls for NGF/BDNF and Osteocalcin respectively. The role of oxitocin(<i>Oxt</i>) and its receptor(<i>Oxtr</i>) was also investigated. <i>Ngf</i> expression shows an opposite trend compared to <i>Bdnf</i>. <i>Ngf</i> /<i>p75NTR</i> expression is 50% higher in BAT than brain, in both genders, but lower in bone. In contrast, <i>Bdnf</i> expression in bone is higher than in brain, but low in BAT/WAT. We found <i>Osteocalcin</i> gene expressed in brain in both genders, but <i>Gprc6a</i> expression is low in brain and BAT/WAT. As expected, <i>Gprc6a</i> gene is expressed in bone. <i>Oxt</i> gene was markedly expressed in brain, <i>Oxtr</i> in the ovaries and in fat and bone in both genders. <i>Ngf</i> is highly expressed in reproductive tissues and <i>p75NTR</i> mRNA levels are respectively 300, 100, and 50% higher in testis/ovaries/uterus than in brain. In contrast, BDNF genes are not expressed in reproductive tissues. As expected, <i>Gprc6a</i> is expressed in testis but not in the ovaries/uterus. A significant correlation was found between the expression levels of the gene ligands and their receptors in brain, BAT and testis suggesting a common pathway of different genes in these tissues in either male and female. Changes in the expression levels of <i>osteocalcin, Ngf</i>, or <i>Bdnf</i> genes may mutually affect the expression levels of the others. Moreover, it may be possible that different ligands may operate through different receptor subtypes. <i>Oxt</i> and <i>Oxtr</i> failed to show significant correlation. The up-regulation of <i>Ngf</i> /<i>p75NTR</i> in BAT is consistent with NGF as an energy regulator and with BDNF regulating bone.