PMID- 26388293 OWN - NLM STAT- MEDLINE DCOM- 20160818 LR - 20151029 IS - 1365-2826 (Electronic) IS - 0953-8194 (Linking) VI - 27 IP - 11 DP - 2015 Nov TI - Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity. PG - 850-60 LID - 10.1111/jne.12324 [doi] AB - 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. CI - (c) 2015 British Society for Neuroendocrinology. FAU - Naert, G AU - Naert G AD - Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France. AD - University of Montpellier, Montpellier, France. AD - EPHE, Paris, France. FAU - Zussy, C AU - Zussy C AD - Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France. AD - University of Montpellier, Montpellier, France. AD - EPHE, Paris, France. FAU - Tran Van Ba, C AU - Tran Van Ba C AD - Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France. AD - University of Montpellier, Montpellier, France. AD - EPHE, Paris, France. FAU - Chevallier, N AU - Chevallier N AD - Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France. AD - University of Montpellier, Montpellier, France. AD - EPHE, Paris, France. FAU - Tang, Y-P AU - Tang YP AD - Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, LA, USA. FAU - Maurice, T AU - Maurice T AD - Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France. AD - University of Montpellier, Montpellier, France. AD - EPHE, Paris, France. FAU - Givalois, L AU - Givalois L AD - Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, U1198 Montpellier, France. AD - University of Montpellier, Montpellier, France. AD - EPHE, Paris, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neuroendocrinol JT - Journal of neuroendocrinology JID - 8913461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Small Interfering) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - W980KJ009P (Corticosterone) SB - IM MH - Adrenocorticotropic Hormone/blood MH - Amygdala/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Corticosterone/blood MH - Frontal Lobe/metabolism MH - Hippocampus/metabolism MH - Hypothalamo-Hypophyseal System/*metabolism MH - Hypothalamus/metabolism MH - Injections, Intraventricular MH - Male MH - Mice MH - Pituitary Gland/metabolism MH - Pituitary-Adrenal System/*metabolism MH - RNA, Small Interfering/administration & dosage/pharmacology MH - Rats MH - Restraint, Physical OTO - NOTNLM OT - ACTH OT - BDNF knockdown mice OT - corticosterone OT - neurotrophin OT - siRNA rat EDAT- 2015/09/22 06:00 MHDA- 2016/08/19 06:00 CRDT- 2015/09/22 06:00 PHST- 2015/01/09 00:00 [received] PHST- 2015/09/03 00:00 [revised] PHST- 2015/09/13 00:00 [accepted] PHST- 2015/09/22 06:00 [entrez] PHST- 2015/09/22 06:00 [pubmed] PHST- 2016/08/19 06:00 [medline] AID - 10.1111/jne.12324 [doi] PST - ppublish SO - J Neuroendocrinol. 2015 Nov;27(11):850-60. doi: 10.1111/jne.12324.