Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats
2019
Tip dokumenta:
Konferencijski prilog (Objavljena verzija)
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© 2019 by the Faculty of Pharmacy, University of Belgrade
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, two to three times more common in women than in men. Because the effects of neuroinflammation on the reproductive status have not been fully explored, our aim was to investigate the impact of experimental autoimmune encephalomyelitis (EAE), the rat model of MS, on hypothalamo-pituitary-gonadal axis. EAE was actively induced in Dark-Agouti rats of both sexes. The animals were examined daily for disease symptoms, weight changes, and estrous cycle phase. The animals were sacrificed at the onset, peak, and end of the disease. Hypothalamic and pituitary tissues were dissected for qRT-PCR analyses. Blood was collected for LH measurements. In separate experiments, groups of male and female animals at the peak of EAE and naïve controls received a subcutaneous injection of buserelin acetate, a potent synthetic GnRH analogue. The obtained data implied that hypothalamic neuroinflammation occurs during onset and/or peak of the disease in both sexes (upregulation of Gfap, Il1b, Il6, Ccl2 and Spp1 mRNA expression). However, hypothalamic Kiss1 and Gnrh mRNA expression was affected differently in males and females, as well as mRNA expression of pituitary signature genes - Lhb, Fshb and Gnrhr. LH levels drop transiently following the course of the disease; in females, this drop coincided with the arrest in diestrus. Nevertheless, the pituitary remained responsive to buserelin treatment. Our results indicate that EAE affects the regulation of hypothalamo-pituitary-gonadal axis in both sexes. Further analyses are needed to elucidate the causes and details of differences in hypothalamic response to neuroinflammation.
Finansiranje / projekti:
- Ćelijska i molekulska osnova neuroinflamacije: potencijala ciljna mesta za translacionu medicinu i terapiju (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41014)
U:
- Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia. Belgrade: Faculty of Pharmacy; 2019. p, 11-2.