Details

Autor(en) / Beteiligte

• Goldfarb, Sean

Titel

The Common Vole (Microtus Arvalis): A Possible New Model Organism for Growth Hormone Neuroendocrinological and Neuroanatomical Studies

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2023

Link zum Volltext

• ProQuest

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Growth hormone (GH) is a neuropeptide produced by the anterior pituitary gland, just ventral to the hypothalamus, that has effects throughout the body, but most notably on growth of the organism. The hypothalamus produces growth hormone-releasing hormone (GHRH), specifically in the arcuate nucleus (ARC), and somatostatin (SOM) in the anterior periventricular nucleus, to stimulate and inhibit, respectively, GH secretion in the anterior pituitary gland. GH is released in a pulsatile manner, with peaks (high hormone levels) and troughs (low hormone levels) throughout the day in mice. To better understand the mechanisms governing this pulsatile release, previous studies in our lab focused on comparing the numbers of synaptic inputs onto GHRH-positive neurons in the ARC during varying levels of GH secretion. This required acquisition of mouse brain tissue that consistently corresponded to either a peak or a trough in GH secretion; since the hormonal status in such experiments is not known before obtaining the brain tissue, this proved to be difficult as the hormone status could not be accurately predicted due to its asynchronous release between animals. As such, to obtain meaningful data, large numbers of mice and a lot of labour were required. Here, I propose the Common Vole (Microtus arvalis) as a potentially better model organism for the study of GH release patterns, with the hope of reducing the required labour and the number of animals needed for a statistically sound study, in line with the “3 Rs” principle in animal experimentation: Replacement, Reduction, and Refinement. Common voles live in communities and interestingly, to avoid predators and to mate, they are well synchronised behaviourally and endocrinologically. However, voles have not been used for such a study thus far. Therefore, we focused on breaking new ground by verifying that they are indeed suitable for our research purposes. Firstly, because the primary antibodies we currently use are known to be reactive against mouse and rats without corresponding data for the vole, we tested various primary antibodies in vole tissue. Secondly, we chose to characterise the vole in relation to mouse in terms of its brain volume, ARC volume, and ARC GHRH and SOM receptor subtype 2 (sst2) cell number, using unbiased stereology. Finally, we and our collaborators aimed to confirm that the individuals in a colony of common voles are indeed more endocrinologically synchronised than mice using a tail-clip blood collection and sandwich ELISA hormone detection method (this data is not shown). Despite some differences, we found promise in the use of Microtus arvalis: our antibodies that work in mouse tissue were also efficacious in vole tissue; the volume of the ARC was not significantly different between vole and mouse (0.21 ± 0.03mm3 and 0.22 ± 0.01mm3, respectively); vole total brain weight was significantly less than that of mouse (0.25 ± 0.01g, and 0.29 ± 0.01g, respectively); voles had significantly lower average sst2-positive cell counts per counting frame than mouse (1.80 ± 0.23 cells and 2.60 ± 0.29 cells, respectively); and the voles showed indications of higher GH-plasma and rest-activity synchronicity than mice.