Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with a widespread occurrence and diverse effects. PACAP has well-documented neuro- and cytoprotective effects, proven in numerous studies. Among others, PACAP is protective in models of diabetes-associated diseases, such as dia...

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Published in:	International journal of molecular sciences Vol. 22; no. 19; p. 10691
Main Authors:	Kiss, Peter, Banki, Eszter, Gaszner, Balazs, Nagy, Daniel, Helyes, Zsuzsanna, Pal, Endre, Reman, Gyongyver, Toth, Gabor, Tamas, Andrea, Reglodi, Dora
Format:	Journal Article
Language:	English
Published:	Basel MDPI AG 01-10-2021 MDPI
Subjects:	Alzheimer's disease Atrophy Body weight Chemical compounds Diabetes Diabetes mellitus Diabetic nephropathy Diabetic neuropathy Diabetic retinopathy dorsal horn Electron microscopy Experiments FosB protein Glucose Hyperalgesia Hyperglycemia Immunohistochemistry Insulin Microscopy Mitochondria Morphology Myelin Nephropathy Nervous system Neuroprotection PACAP Pain Pain perception Peptides periaqueductal grey Pharmacology Physical characteristics Pituitary adenylate cyclase-activating polypeptide Retinopathy Rodents Spinal cord Streptozocin Substantia grisea Thickening
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Summary:	Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with a widespread occurrence and diverse effects. PACAP has well-documented neuro- and cytoprotective effects, proven in numerous studies. Among others, PACAP is protective in models of diabetes-associated diseases, such as diabetic nephropathy and retinopathy. As the neuropeptide has strong neurotrophic and neuroprotective actions, we aimed at investigating the effects of PACAP in a rat model of streptozotocin-induced diabetic neuropathy, another common complication of diabetes. Rats were treated with PACAP1-38 every second day for 8 weeks starting simultaneously with the streptozotocin injection. Nerve fiber morphology was examined with electron microscopy, chronic neuronal activation in pain processing centers was studied with FosB immunohistochemistry, and functionality was assessed by determining the mechanical nociceptive threshold. PACAP treatment did not alter body weight or blood glucose levels during the 8-week observation period. However, PACAP attenuated the mechanical hyperalgesia, compared to vehicle-treated diabetic animals, and it markedly reduced the morphological signs characteristic for neuropathy: axon–myelin separation, mitochondrial fission, unmyelinated fiber atrophy, and basement membrane thickening of endoneurial vessels. Furthermore, PACAP attenuated the increase in FosB immunoreactivity in the dorsal spinal horn and periaqueductal grey matter. Our results show that PACAP is a promising therapeutic agent in diabetes-associated complications, including diabetic neuropathy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms221910691