Accelerated retinal aging in PACAP knock-out mice

Andrea Kovács-Valasek, K. Szabadfi, Viktória Dénes, Bálint Szalontai, A. Tamás, P. Kiss, A. Szabó, Gyorgy Setalo, D. Reglodi, R. Gábriel

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide. PACAP and its receptors are widely distributed in the retina. A number of reports provided evidence that PACAP is neuroprotective in retinal degenerations. The current study compared retina cell type-specific differences in young (3–4 months) and aged adults (14–16 months), of wild-type (WT) mice and knock-out (KO) mice lacking endogenous PACAP production during the course of aging. Histological, immunocytochemical and Western blot examinations were performed. The staining for standard neurochemical markers (tyrosine hydroxylase for dopaminergic cells, calbindin 28 kDa for horizontal cells, protein kinase Cα for rod bipolar cells) of young adult PACAP KO retinas showed no substantial alterations compared to young adult WT retinas, except for the specific PACAP receptor (PAC1-R) staining. We could not detect PAC1-R immunoreactivity in bipolar and horizontal cells in young adult PACAP KO animals. Some other age-related changes were observed only in the PACAP KO mice only. These alterations included horizontal and rod bipolar cell dendritic sprouting into the photoreceptor layer and decreased ganglion cell number. Also, Müller glial cells showed elevated GFAP expression compared to the aging WT retinas. Furthermore, Western blot analyses revealed significant differences between the phosphorylation state of ERK1/2 and JNK in KO mice, indicating alterations in the MAPK signaling pathway. These results support the conclusion that endogenous PACAP contributes to protection against aging of the nervous system.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalNeuroscience
Volume348
DOIs
Publication statusPublished - Apr 21 2017

Keywords

  • immunocytochemistry
  • Müller glia
  • pituitary adenylate cyclase activating polypeptide
  • retina neurons
  • Western blot

ASJC Scopus subject areas

  • Neuroscience(all)

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