title: Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity.
abstract: Brain-derived neurotrophic factor (BDNF) appears to be highly involved in hypothalamic-pituitary-adrenal (HPA) axis regulation during adulthood, playing an important role in homeostasis maintenance. The present study aimed to determine the involvement of BDNF in HPA axis activity under basal and stress conditions via partial inhibition of this endogenous neurotrophin. Experiments were conducted in rats and mice with two complementary approaches: (i) BDNF knockdown with stereotaxic delivery of BDNF-specific small interfering RNA (siRNA) into the lateral ventricle of adult male rats and (ii) genetically induced knockdown (KD) of BDNF expression specifically in the central nervous system during the first ontogenesis in mice (KD mice). Delivery of siRNA in the rat brain decreased BDNF levels in the hippocampus (-31%) and hypothalamus (-35%) but not in the amygdala, frontal cortex and pituitary. In addition, siRNA induced no change of the basal HPA axis activity. BDNF siRNA rats exhibited decreased BDNF levels and concomitant altered adrenocortoctrophic hormone (ACTH) and corticosterone responses to restraint stress, suggesting the involvement of BDNF in the HPA axis adaptive response to stress. In KD mice, BDNF levels in the hippocampus and hypothalamus were decreased by 20% in heterozygous and by 60% in homozygous animals compared to wild-type littermates. Although, in heterozygous KD mice, no significant change was observed in the basal levels of plasma ACTH and corticosterone, both hormones were significantly increased in homozygous KD mice, demonstrating that robust cerebral BDNF inhibition (60%) is necessary to affect basal HPA axis activity. All of these results in both rats and mice demonstrate the involvement and importance of a robust endogenous pool of BDNF in basal HPA axis regulation and the pivotal function of de novo BDNF synthesis in the establishment of an adapted response to stress.
authors.affiliation: Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France.|University of Montpellier, Montpellier, France.|EPHE, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Naert
authors.affiliation: Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France.|University of Montpellier, Montpellier, France.|EPHE, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Zussy
authors.affiliation: Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France.|University of Montpellier, Montpellier, France.|EPHE, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Tran Van Ba
authors.affiliation: Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France.|University of Montpellier, Montpellier, France.|EPHE, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Chevallier
authors.affiliation: Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, LA, USA.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Tang
authors.affiliation: Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France.|University of Montpellier, Montpellier, France.|EPHE, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Maurice
authors.affiliation: Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France.|University of Montpellier, Montpellier, France.|EPHE, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Givalois
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D012149:Restraint, Physical
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D034741:RNA, Small Interfering; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: ACTH; BDNF knockdown mice; corticosterone; neurotrophin; siRNA rat