Date of Award
Master of Science
Dr. Valerie Hedges
The recently discovered novel neuropeptide transmembrane protein 35 (TMEM35), is believed to modulate chemical signaling within the nervous system. Notably, the TMEM35 protein is detectable in humans, non-human primates and rodents, suggesting a conserved and critical function. Despite this, the functions of TMEM35 are ill-defined in the nervous system and insufficiently studied (currently only three publications). Previous work has identified high expression of TMEM35 in both the ventromedial hypothalamus (VMH) and the limbic circuit of the mouse brain. Due to the known functions of these two regions, this pattern of expression indicates possible roles of this neuropeptide in social behavior and reward processing. Interestingly, TMEM35 mRNA expression exhibits possible sexual dimorphisms in rodents with the overall expression of TMEM35 mRNA being higher in females than in males. However, this qualitative evaluation of sex differences in mRNA expression has not been quantitatively described throughout the brains of male and female rodents. We aimed to anatomically map TMEM35 protein expression in both male and female Syrian hamsters to determine sex differences in expression. Moreover, we hypothesized that ovarian hormones were responsible for the observed sex differences in females. To determine this, we ovariectomized adult female Syrian hamsters to remove the major endogenous source of gonadal steroid hormones, and primed them with estradiol and progesterone to mimic the natural hormonal cycle, or with cottonseed oil vehicle. Tissue was immunohistochemically processed for TMEM35-positive cells. Sex differences in TMEM35 protein expression in which females expressed higher levels than males were found in several brain areas, including in the anterior hypothalamic nucleus (AH), anteroventral periventricular nucleus (AVPV), bed nucleus of the stria terminalis (BNST), dorsomedial hypothalamus (DMH), dorsal lateral septum (LSd), dorsal medial amygdala (MAd), medial caudate (MCU), medial preoptic nucleus (MPN), nucleus accumbens core (NAcc), nucleus accumbens shell (NAcsh), suprachiasmatic nucleus (SCN), and ventromedial hypothalamus (VMH). Of these brain areas, ovarian hormones induced TMEM35 expression in the AH, CA1 of the hippocampal formation, MAd, MCU, NAcsh, PVN, and VMHm. Characterizing how TMEM35 expression is altered as a result of engaging in normal life experiences will give insight into the biology of brain circuitry, and will provide better understanding into how these systems function and could potentially lead to the development of therapeutic treatments to alleviate dysfunctions within each network.
Vanderplow, Amanda M., "CHARACTERIZATION OF TRANSMEMBRANE PROTEIN 35 EXPRESSION: CONSIDERATIONS OF SEX AND OVARIAN HORMONES" (2017). All NMU Master's Theses. 155.