Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers

Viktória Kormos, László Gáspár, László Kovács, József Farkas, Tamás Gaszner, V. Csernus, András Balogh, Hitoshi Hashimoto, D. Reglodi, Z. Helyes, B. Gaszner

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in stress adaptation with potential relevance in mood disorder management. PACAP deficient (KO) mice on CD1 background were shown to have depression-like phenotype. Here we aimed at investigating effects of chronic variable mild stress (CVMS) in non-injected, vehicle and imipramine-treated KO mice vs. wildtype (WT) counterparts. We hypothesized reduced FosB neuronal activity in stress-related centers, altered activity and peptide/neurotransmitter content of corticotropin-releasing factor (CRF) cells of the oval (ovBST) bed nucleus of stria terminalis (BST), urocortin 1 (Ucn1) neurons of centrally projecting Edinger-Westphal nucleus (cpEW) and serotonin (5HT) cells of dorsal raphe (DR) in PACAP deficiency. CVMS caused decreased body weight and increased adrenal size, corticosterone (CORT) titers and depression-like behavior in WT mice, in contrast to KO animals. CVMS increased FosB in the central (CeA) and medial amygdala, dorsomedial (dmBST), ventral (vBST), ovBST, CA1 area, dentate gyrus (DG), ventral lateral septum, parvo- (pPVN) and magnocellular paraventricular nucleus, lateral periaqueductal gray, cpEW and DR. Lack of PACAP blunted the CVMS-induced FosB rise in the CeA, ovBST, dmBST, vBST, CA1 area, pPVN and DR. The CVMS-induced FosB expression in ovBST-CRF and cpEW-Ucn1 neurons was abolished in KO mice. Although CVMS did not induce FosB in 5HT-DR neurons, PACAP KO mice had increased 5HT cell counts and 5HT content. We conclude that PACAP deficiency affects neuronal reactivity in a brain area-specific manner in stress centers, as well as in ovBST-CRF, cpEW-Ucn1 and 5HT-DR neurons leading to reduced CVMS response and altered depression level.

Original languageEnglish
Pages (from-to)335-358
Number of pages24
JournalNeuroscience
Volume330
DOIs
Publication statusPublished - Aug 25 2016

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Pituitary Adenylate Cyclase-Activating Polypeptide
Prosencephalon
Brain Stem
Urocortins
Corticotropin-Releasing Hormone
Neurons
Depression
Septal Nuclei
Periaqueductal Gray
Paraventricular Hypothalamic Nucleus
Imipramine
Dentate Gyrus
Corticosterone
Mood Disorders
Neurotransmitter Agents
Serotonin
Cell Count
Body Weight
Dorsal Raphe Nucleus
Phenotype

Keywords

  • Corticotropin-releasing factor
  • Dorsal raphe nucleus
  • FosB
  • Serotonin
  • Stress
  • Urocortin 1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers. / Kormos, Viktória; Gáspár, László; Kovács, László; Farkas, József; Gaszner, Tamás; Csernus, V.; Balogh, András; Hashimoto, Hitoshi; Reglodi, D.; Helyes, Z.; Gaszner, B.

In: Neuroscience, Vol. 330, 25.08.2016, p. 335-358.

Research output: Contribution to journalArticle

Kormos, Viktória ; Gáspár, László ; Kovács, László ; Farkas, József ; Gaszner, Tamás ; Csernus, V. ; Balogh, András ; Hashimoto, Hitoshi ; Reglodi, D. ; Helyes, Z. ; Gaszner, B. / Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers. In: Neuroscience. 2016 ; Vol. 330. pp. 335-358.
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AU - Farkas, József

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AU - Csernus, V.

AU - Balogh, András

AU - Hashimoto, Hitoshi

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AU - Helyes, Z.

AU - Gaszner, B.

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N2 - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in stress adaptation with potential relevance in mood disorder management. PACAP deficient (KO) mice on CD1 background were shown to have depression-like phenotype. Here we aimed at investigating effects of chronic variable mild stress (CVMS) in non-injected, vehicle and imipramine-treated KO mice vs. wildtype (WT) counterparts. We hypothesized reduced FosB neuronal activity in stress-related centers, altered activity and peptide/neurotransmitter content of corticotropin-releasing factor (CRF) cells of the oval (ovBST) bed nucleus of stria terminalis (BST), urocortin 1 (Ucn1) neurons of centrally projecting Edinger-Westphal nucleus (cpEW) and serotonin (5HT) cells of dorsal raphe (DR) in PACAP deficiency. CVMS caused decreased body weight and increased adrenal size, corticosterone (CORT) titers and depression-like behavior in WT mice, in contrast to KO animals. CVMS increased FosB in the central (CeA) and medial amygdala, dorsomedial (dmBST), ventral (vBST), ovBST, CA1 area, dentate gyrus (DG), ventral lateral septum, parvo- (pPVN) and magnocellular paraventricular nucleus, lateral periaqueductal gray, cpEW and DR. Lack of PACAP blunted the CVMS-induced FosB rise in the CeA, ovBST, dmBST, vBST, CA1 area, pPVN and DR. The CVMS-induced FosB expression in ovBST-CRF and cpEW-Ucn1 neurons was abolished in KO mice. Although CVMS did not induce FosB in 5HT-DR neurons, PACAP KO mice had increased 5HT cell counts and 5HT content. We conclude that PACAP deficiency affects neuronal reactivity in a brain area-specific manner in stress centers, as well as in ovBST-CRF, cpEW-Ucn1 and 5HT-DR neurons leading to reduced CVMS response and altered depression level.

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