title: The behavioral phenotype of pituitary adenylate-cyclase activating polypeptide-deficient mice in anxiety and depression tests is accompanied by blunted c-Fos expression in the bed nucleus of the stria terminalis, central projecting Edinger-Westphal nucleus, ventral lateral septum, and dorsal raphe nucleus.
abstract: Pituitary adenylate-cyclase activating polypeptide (PACAP) has been implicated in the (patho)physiology of stress-adaptation. PACAP deficient (PACAP(-/-)) mice show altered anxiety levels and depression-like behavior, but little is known about the underlying mechanisms in stress-related brain areas. Therefore, we aimed at investigating PACAP(-/-) mice in light-dark box, marble burying, open field, and forced swim paradigms. We also analyzed whether the forced swim test-induced c-Fos expression would be affected by PACAP deficiency in the following stress-related brain areas: magno- and parvocellular paraventricular nucleus of the hypothalamus (PVN); basolateral (BLA), medial (MeA), and central (CeA) amygdaloid nuclei; ventral (BSTv), dorsolateral (BSTdl), dorsomedial (BSTdm), and oval (BSTov) nuclei of the bed nucleus of stria terminalis; dorsal (dLS) and ventral parts (vLS) of lateral septal nucleus, central projecting Edinger-Westphal nucleus (EWcp), dorsal (dPAG) and lateral (lPAG) periaqueductal gray matter, dorsal raphe nucleus (DR). Our results revealed that PACAP(-/-) mice showed greatly reduced anxiety and increased locomotor activity compared with wildtypes. In forced swim test PACAP(-/-) mice showed increased depression-like behavior. Forced swim exposure increased c-Fos expression in all examined brain areas in wildtypes, whereas this was markedly blunted in the DR, EWcp, BSTov, BSTdl, BSTv, PVN, vLS, dPAG, and in the lPAG of PACAP(-/-) mice vs. wildtypes, strongly suggesting their involvement in the behavioral phenotype of PACAP(-/-) mice. PACAP deficiency did not influence the c-Fos response in the CeA, MeA, BSTdm, and dLS. Therefore, we propose that PACAP exerts a brain area-specific effect on stress-induced neuronal activation and it might contribute to stress-related mood disorders.
authors.affiliation: Department of Anatomy, PTE-MTA Lendület PACAP Research Team, University of Pécs, Faculty of Medicine, H-7624, Pécs, Szigeti u. 12., Hungary. balazs.b.gaszner@aok.pte.hu
authors.forename: B
authors.initials: B
authors.lastname: Gaszner
authors.forename: V
authors.initials: V
authors.lastname: Kormos
authors.forename: T
authors.initials: T
authors.lastname: Kozicz
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: D
authors.initials: D
authors.lastname: Reglodi
authors.forename: Z
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000502:physiology*; D003863:Depression / Q000523:psychology*; D005726:Ganglia, Parasympathetic / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D016762:Genes, fos / Q000235:genetics / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009802:Oculomotor Nerve / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency* / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000378:metabolism*; D012686:Septal Nuclei / Q000378:metabolism*; D020665:Septum of Brain / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos