Life Sciences & Biotechnology
Title : | Investigating the significance of V2 and V3 variants of the gonadotropin releasing hormone (GnRH) in the hypothalamic and non-hypothalamic neurons: new insights in neuronal physiology |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Neuroscience |
Principal Investigator : | Dr. Arnab Banerjee, Birla Institute Of Technology & Science Pilani (BITS), Goa |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | arnabb@goa.bits-pilani.ac.in |
Details
Executive Summary : | The hypothalamic gonadotropin releasing hormone (GnRH) is one of the key hormones regulating the reproductive system and other important physiological processes among several animal taxa. Adequate knowledge about GnRH is not only important for understanding reproduction but also for the other non-reproductive roles of it in neurons among human and animals. GnRH gene undergoes alternative splicing to produce three variants; the functional variant, V1, which codes for the GnRH and the GnRH-associated peptide (GAP) peptide, and two other alternative splice variants, V2 and V3 respectively, and there exists very few studies about these variants. Recently, from Pi’s group it has been shown that there is an age dependent variation in these variants, V2 and V3, in the hypothalamus and in other regions of the brain. The study had also shown the presence of translation repressors site on the V3 RNA thus responsible for its reported low efficiency of translation. Knowledge about how the V2 and V3 variants varies within hypothalamic and non-hypothalamic neurons when such neurons are treated with known regulators of V1 (GnRH) regulators such as kisspeptin and polyamines or metabolic regulators is not yet known. Also, the scenario of the splicing factors after such treatment is unknown. Like GnRH, a lot of other genes undergo alternative splicing in the brain, and recently some of the alternatively spliced genes in the brain have been associated to be markers of certain disorders/ physiological processes. Knowing more about these variants and splicing mechanism in the hypothalamic and non-hypothalamic neurons will be a significant input into neuronal physiology. Finally, the physiological significance or role of the V2 and V3 variants of GnRH in hypothalamic and non-hypothalamic neurons are not yet known. The present proposal aims to investigate the variation of V2 and V3 variants in the hypothalamic and non-hypothalamic neurons after treatment with known GnRH regulators (such as kisspeptin and polyamine) and metabolic regulators (such as TNF-α and lactate). The work will further look into the scenario of splicing factors after such treatments in both hypothalamic and non-hypothalamic neurons. Furthermore, the proposal aims to unravel the role(s) of V2 and V3 variants in the hypothalamic and non-hypothalamic neurons if any. Owing to the fact that hypothalamus is the center controlling reproduction, stress, energy metabolism and wake sleep cycle, role of these variants in regulating any of these will be very novel and significant in the field of neuronal physiology. Also, illustrating the non-reproductive roles of these in a non-hypothalamic neuron will be of great importance. |
Co-PI: | Dr. Indrani Talukdar, Birla Institute Of Technology & Science Pilani (BITS), Sancoale,Goa-403726 |
Total Budget (INR): | 55,76,670 |
Organizations involved