Investigation of the effects of vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide on amyotrophic lateral sclerosis pathogenesis

Aim: The aim of this thesis study was to investigate and compare the effects of VIP and PACAP-38 on lower and upper motor neurons in SOD1G93A ALS model mice. Method: Experimental groups were formed using transgenic SOD1G93A and wild-type mice, consisting of Control (n=10), ALS+SF (n=10), ALS+VIP (n=10), and ALS+PACAP (n=10). While intraperitoneal (i.p.) injections of physiological saline were administered to the ALS+SF group, the ALS+VIP group received i.p. injections of 5 nmol/kg VIP, and the ALS+PACAP group received i.p. injections of 25 ng/kg PACAP-38. At pre-symptomatic day 30, ultrastructural changes in lower motor neurons, and at symptomatic day 105, brain chemistry, quantification of lower motor neurons and dendritic spine densities, and microglial morphology were evaluated. After post-symptomatic day 120, weight, motor performance, and survival assessments were conducted, followed by the evaluation of gene expressions of inflammatory markers and growth factors in the lumbar spinal cord tissue. Results: The ultrastructural integrity in the lumbar spinal cord of the ALS+SF group, which were compromised, exhibited a morphology similar to the Control group in the treatment groups. The ALS+PACAP group showed a significant increase in both motor neuron count and dendritic spine density, while the ALS+VIP group showed a significant increase only in dendritic spine density compared to the ALS+SF group. Additionally, the number of reactive microglia was significantly reduced in the treatment groups compared to the ALS+SF group. Motor performance significantly improved in the ALS+PACAP group, and both treatment groups experienced a significantly longer survival time compared to the ALS+SF group. Conclusion: In conclusion, PACAP-38 appears to be more effective in SOD1G93A ALS model mice, but both VIP and PACAP-38 demonstrated therapeutic efficacy.