title: Companions reverse stressor-induced decreases in neurogenesis and cocaine conditioning possibly by restoring BDNF and NGF levels in dentate gyrus.
abstract: The presence of companions can reverse the stressor-induced decrease in neurogenesis in mouse dentate gyrus (DG). In this study, we decided to study the underlying mechanisms of the companions' protective effect and to assess whether two DG neurogenesis-related memories, cocaine-induced conditioned place preference (CPP) and spatial memory, can be affected by our stressor and companions. Neurotrophin levels in DG were measured, in this regard, to reveal their roles in mediating the stressors' and companions' effect. We found that the stressor did not affect NT-3 but acutely decreased NGF and BDNF levels in DG. The presence of companions abolished these stressor-decreased NGF and BDNF levels. Neither the stressor nor the presence of companions affected TrkA, TrkB or TrkC expression in DG. Pre-exposure to the stressor rendered deficits in cocaine-induced CPP and spatial memory, while companions reversed the stressor-decreased cocaine-induced CPP. Intra-ventricular infusion with K252a, a mixed TrkA and TrkB antagonist, did not affect the protective effects of companions on local NGF, BDNF levels in DG, but abolished the companions' protective effects against the stressor-decreased DG neurogenesis and cocaine-induced CPP. Systemic pretreatment with 7,8-dihydroxyflavone (DHF), a selective TrkB agonist, did not affect baseline, the stressor-stimulated corticosterone (CORT) secretion or local NGF, BDNF levels in DG, but in part mimicked companions' protective effects. These results, taken together, indicate that stressor-decreased NGF and BDNF levels in DG could be involved in the stressor-decreased DG neurogenesis and cocaine conditioning. The presence of companions reverses the stressor-decreased DG neurogenesis and cocaine conditioning possibly by restoring BDNF and NGF levels in DG.
authors: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC.
authors: Wen-Yu
authors: WY
authors: Tzeng
authors: Jia-Ying
authors: JY
authors: Chuang
authors: Li-Ching
authors: LC
authors: Lin
authors: Chianfang G
authors: CG
authors: Cherng
authors: Kuei-Ying
authors: KY
authors: Lin
authors: Li-Hsien
authors: LH
authors: Chen
authors: Chien-Chou
authors: CC
authors: Su
authors: Lung
authors: L
authors: Yu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000502:physiology*; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology; D033062:Friends; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D057967:Infusions, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D020813:Receptor, trkB / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*
chemical_list: C485383:6,7-dihydroxyflavone; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D047309:Flavones; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D047428:Protein Kinase Inhibitors; C518911:neurotropin 3, mouse; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; D003345:Corticosterone