{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:13:17Z","timestamp":1772784797551,"version":"3.50.1"},"reference-count":129,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["FK129190, K135457, K119759"],"award-info":[{"award-number":["FK129190, K135457, K119759"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Brain Research Program","award":["NAP2017-1.2.1-NKP-2017-00002"],"award-info":[{"award-number":["NAP2017-1.2.1-NKP-2017-00002"]}]},{"DOI":"10.13039\/501100004633","name":"MTA","doi-asserted-by":"publisher","award":["14016"],"award-info":[{"award-number":["14016"]}],"id":[{"id":"10.13039\/501100004633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"GINOP","award":["GINOP-2.3.2-15-2016-00050 \u201cPEPSYS\u201d"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00050 \u201cPEPSYS\u201d"]}]},{"name":"EFOP","award":["EFOP-3.6.2-16-2017-00008; EFOP-3.6.3-00009; EFOP-3.6.1-16-2016-00004"],"award-info":[{"award-number":["EFOP-3.6.2-16-2017-00008; EFOP-3.6.3-00009; EFOP-3.6.1-16-2016-00004"]}]},{"name":"Kivalosagi Program","award":["20765\/3\/2018\/FEKUTSTRAT, 2020-4.1.1-TKP2020\u2014FIKP III"],"award-info":[{"award-number":["20765\/3\/2018\/FEKUTSTRAT, 2020-4.1.1-TKP2020\u2014FIKP III"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013myelin 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.<\/jats:p>","DOI":"10.3390\/ijms221910691","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T09:24:15Z","timestamp":1633339455000},"page":"10691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy"],"prefix":"10.3390","volume":"22","author":[{"given":"Peter","family":"Kiss","sequence":"first","affiliation":[{"name":"Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eszter","family":"Banki","sequence":"additional","affiliation":[{"name":"Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2830-2732","authenticated-orcid":false,"given":"Balazs","family":"Gaszner","sequence":"additional","affiliation":[{"name":"Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6525-0754","authenticated-orcid":false,"given":"Endre","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pecs Clinical Centre, Ret utca 2, H-7623 Pecs, Hungary"},{"name":"Neuropathology Unit, Department of Pathology, University of Pecs Clinical Centre, Rakoczi ut 2, H-7623 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyongyver","family":"Reman","sequence":"additional","affiliation":[{"name":"Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor","family":"Toth","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Dom ter 8, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Tamas","sequence":"additional","affiliation":[{"name":"Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora","family":"Reglodi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Szentagothai Research Centre, University of Pecs Medical School, Szigeti ut 12, H-7624 Pecs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1124\/pr.109.001370","article-title":"Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 Years after the discovery","volume":"61","author":"Vaudry","year":"2009","journal-title":"Pharmacol. 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