title: Accelerated retinal aging in PACAP knock-out mice.
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 (3-4months) and aged adults (14-16months), 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.
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary; Department of János Szentágothai Research Center, University of Pécs, Pécs, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovács-Valasek
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szabadfi
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Dénes
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Szalontai
authors.affiliation: Department of Anatomy, University of Pécs, Pécs, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamás
authors.affiliation: Department of Anatomy, University of Pécs, Pécs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Kiss
authors.affiliation: Department of Biochemistry and Medicinal Chemistry, University of Pécs, Pécs, Hungary.
authors.forename: Aliz
authors.initials: A
authors.lastname: Szabó
authors.affiliation: Department of Medical Biology, University of Pécs, Pécs, Hungary; Department of János Szentágothai Research Center, University of Pécs, Pécs, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Setalo
authors.affiliation: Department of Anatomy, University of Pécs, Pécs, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Reglődi
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary; Department of János Szentágothai Research Center, University of Pécs, Pécs, Hungary. Electronic address: gabriel@ttk.pte.hu.
authors.forename: Robert
authors.initials: R
authors.lastname: Gábriel
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D064026:Calbindins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D014446:Tyrosine 3-Monooxygenase; D051571:Protein Kinase C-alpha
keywords: Müller glia; Western blot; immunocytochemistry; pituitary adenylate cyclase activating polypeptide; retina neurons