TY - JOUR AU - Huzián, Orsolya AU - Baka, Judith AU - Csákvári, Eszter AU - Dobos, Nikoletta AU - Leranth, Csaba AU - Siklós, László AU - Duman, Ronald S AU - Farkas, Tamás AU - Hajszán, Tibor TI - Stress Resilience Is Associated with Hippocampal Synaptoprotection in the Female Rat Learned Helplessness Paradigm. JF - NEUROSCIENCE J2 - NEUROSCIENCE VL - 459 PY - 2021 SP - 85 EP - 103 PG - 19 SN - 0306-4522 DO - 10.1016/j.neuroscience.2021.01.029 UR - https://m2.mtmt.hu/api/publication/31850252 ID - 31850252 N1 - Cited By :3 Export Date: 14 September 2022 CODEN: NRSCD AB - The synaptogenic hypothesis of major depressive disorder implies that preventing the onset of depressive-like behavior also prevents the loss of hippocampal spine synapses. By applying the psychoactive drugs, diazepam and fluoxetine, we investigated whether blocking the development of helpless behavior by promoting stress resilience in the rat learned helplessness paradigm is associated with a synaptoprotective action in the hippocampus. Adult ovariectomized and intact female Sprague-Dawley rats (n=297) were treated with either diazepam, fluoxetine, or vehicle, exposed to inescapable footshocks or sham stress, and tested in an active escape task to assess helpless behavior. Escape-evoked corticosterone secretion, as well as remodeling of hippocampal spine synapses at a timepoint representing the onset of escape testing were also analyzed. In ovariectomized females, treatment with diazepam prior to stress exposure prevented helpless behavior, blocked the loss of hippocampal spine synapses, and muted the corticosterone surge evoked by escape testing. Although fluoxetine stimulated escape performance and hippocampal synaptogenesis under non-stressed conditions, almost all responses to fluoxetine were abolished following exposure to inescapable stress. Only a much higher dose of fluoxetine was capable of partly reproducing the strong protective actions of diazepam. Importantly, these protective actions were retained in the presence of ovarian hormones. Our findings indicate that stress resilience is associated with the preservation of spine synapses in the hippocampus, raising the possibility that, besides synaptogenesis, hippocampal synaptoprotection is also implicated in antidepressant therapy. LA - English DB - MTMT ER - TY - JOUR AU - Hajszán, Tibor TI - Stress and remodeling of hippocampal spine synapses JF - VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS J2 - VITAM HORM VL - 114 PY - 2020 SP - 257 EP - 279 PG - 23 SN - 0083-6729 DO - 10.1016/bs.vh.2020.04.007 UR - https://m2.mtmt.hu/api/publication/31408884 ID - 31408884 N1 - Export Date: 9 September 2020 CODEN: VIHOA Correspondence Address: Hajszan, T.; Institute of Biophysics, Biological Research CenterHungary; email: hajszan.tibor@brc.hu Export Date: 10 September 2020 CODEN: VIHOA Correspondence Address: Hajszan, T.; Institute of Biophysics, Biological Research CenterHungary; email: hajszan.tibor@brc.hu Cited By :1 Export Date: 16 April 2021 CODEN: VIHOA Correspondence Address: Hajszan, T.; Institute of Biophysics, Hungary; email: hajszan.tibor@brc.hu Funding details: National Research, Development and Innovation Office, GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00034 Funding text 1: This work was supported by the Hungarian National Research, Development, and Innovation Office [grant numbers GINOP-2.3.2-15-2016-00001 and GINOP-2.3.2-15-2016-00034]. The author wishes to thank his colleagues, Nora Lakatos and Roland Patai, for generating the electron microscopic preparation of Fig. 1 . AB - By nature's original design, stress is a protective mechanism, signaling danger to homeostasis and, as a result, stimulating the brain to initiate coping and adaptive responses, which ultimately increases the chances of survival. On the other hand, stress may become a danger to homeostasis itself, when it is so severe or so prolonged that it overpowers cellular reserves. One of the consequences of traumatic stress is loss of hippocampal spine synapses, which is the main topic of this chapter summarizing research findings from the last 10 + years. Loss of spine synapses is thought to be a neuronal defense mechanism against excitotoxic damage, so the subcellular mechanisms of synapse loss are reviewed in the context of glutamatergic insults. One of the main conceptual derivates of stress-induced synaptic alterations is the “synaptogenic” hypothesis of major depressive disorder. The synaptogenic hypothesis postulates an inverse correlation between the number of limbic, mainly prefrontal cortical and hippocampal, spine synapses and the severity of depressive behavior/symptoms. The synaptogenic hypothesis implies that synaptoprotective interventions, that are capable of countering the stress-induced loss of limbic spine synapses, are probably also capable of promoting stress resilience, which may provide the conceptual basis for a preventive approach in antidepressant therapy. Finally, we discuss why electron microscopic stereology is a reliable and highly accurate technique for the quantitative assessment of ultrastructural particulate objects, such as spines and synapses. © 2020 Elsevier Inc. LA - English DB - MTMT ER - TY - GEN AU - Lakatos, Nóra AU - Polgár, Tamás Ferenc AU - Patai, Roland AU - Siklos, L AU - Hajszán, Tibor TI - Effects of N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamine (SZR-72) in the rat learned helplessness paradigm PY - 2019 UR - https://m2.mtmt.hu/api/publication/30740997 ID - 30740997 N1 - 30723383 másolata. poster AB - Poster LA - English DB - MTMT ER - TY - GEN AU - Hajszán, Tibor AU - Baka, Judith AU - Huzián, Orsolya AU - Csákvári, Eszter AU - Dobos, Nikoletta AU - Siklos, L TI - Potential role of synaptoprotection in mood disorders PY - 2017 UR - https://m2.mtmt.hu/api/publication/30658997 ID - 30658997 AB - Lecture LA - English DB - MTMT ER - TY - JOUR AU - Baka, Judith AU - Csákvári, Eszter AU - Huzián, Orsolya AU - Dobos, Nikoletta AU - Siklós, László AU - Leranth, C AU - Maclusky, NJ AU - Duman, RS AU - Hajszán, Tibor TI - STRESS INDUCES EQUIVALENT REMODELING OF HIPPOCAMPAL SPINE SYNAPSES IN A SIMULATED POSTPARTUM ENVIRONMENT AND IN A FEMALE RAT MODEL OF MAJOR DEPRESSION JF - NEUROSCIENCE J2 - NEUROSCIENCE VL - 343 PY - 2017 SP - 384 EP - 397 PG - 14 SN - 0306-4522 DO - 10.1016/j.neuroscience.2016.12.021 UR - https://m2.mtmt.hu/api/publication/3202535 ID - 3202535 N1 - Megjegyzés-26385888 N1 Funding details: MB08C OTKA 81190, OTKA, Országos Tudományos Kutatási Alapprogramok N1 Funding details: MH074021, NIMH, National Institute of Mental Health N1 Funding text: This study was supported by a NARSAD Young Investigator Award, a National Institute of Mental Health (NIMH) grant [grant number MH074021], a Research, Technology and Innovation Fund (KTIA, Hungary) and Hungarian Scientific Research Fund (OTKA) joint reintegration grant [grant number Mobility MB08C OTKA 81190], and European Union and New Szechenyi Programme (ÚSZT, Hungary) joint grants [grant numbers TÁMOP-4.2.2.A-11/1/KONV-2012-0052, TÁMOP-4.2.4.A/2-11-1-2012-0001, and GINOP-2.3.2-15-2016-00001]. Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, Szeged, 6726, Hungary Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road E, Guelph, Ontario N1G 2W1, Canada Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, United States Cited By :3 Export Date: 11 February 2020 CODEN: NRSCD Correspondence Address: Hajszan, T.; Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, Hungary Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, Szeged, 6726, Hungary Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road E, Guelph, Ontario N1G 2W1, Canada Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, United States Cited By :9 Export Date: 16 April 2021 CODEN: NRSCD Correspondence Address: Hajszan, T.; Institute of Biophysics, Temesvari Krt 62, Hungary Chemicals/CAS: corticosterone, 50-22-6; estradiol, 50-28-2; progesterone, 57-83-0; Corticosterone; Estradiol; Progesterone Funding details: A/2-11-1-2012-0001, GINOP-2.3.2-15-2016-00001, T?MOP-4.2.2 Funding details: National Institute of Mental Health, NIMH, R01MH074021, R01MH105910, T32MH014276 Funding details: National Alliance for Research on Schizophrenia and Depression, NARSAD Funding details: Hungarian Scientific Research Fund, OTKA, MB08C OTKA 81190 Funding text 1: This study was supported by a NARSAD Young Investigator Award, a National Institute of Mental Health (NIMH) grant [grant number MH074021], a Research, Technology and Innovation Fund (KTIA, Hungary) and Hungarian Scientific Research Fund (OTKA) joint reintegration grant [grant number Mobility MB08C OTKA 81190], and European Union and New Szechenyi Programme (?SZT, Hungary) joint grants [grant numbers T?MOP-4.2.2.A-11/1/KONV-2012-0052, T?MOP-4.2.4.A/2-11-1-2012-0001, and GINOP-2.3.2-15-2016-00001]. AB - Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague Dawley rats (n = 76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn 'postpartum', simulated proestrus, and hormone-treated 'postpartum' animals. After 'postpartum' withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn 'postpartum' females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during 'postpartum' stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during 'postpartum' stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated 'postpartum' females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging 'synaptogenic hypothesis' of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness. (C) 2016 IBRO. Published by Elsevier Ltd. 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LA - English DB - MTMT ER - TY - GEN AU - Huzian, O AU - Baka, J AU - Dobos, N AU - Csakvari, E AU - Siklos, L AU - Hajszán, Tibor TI - Investigation of sex differences in major depression using the active escape paradigm in rats PY - 2014 UR - https://m2.mtmt.hu/api/publication/30659948 ID - 30659948 AB - Poster LA - English DB - MTMT ER - TY - GEN AU - Huzian, O AU - Baka, J AU - Dobos, N AU - Csakvari, E AU - Siklos, L AU - Hajszán, Tibor TI - Investigation of sex differences in major depression using the learned helplessness paradigm in rats PY - 2014 UR - https://m2.mtmt.hu/api/publication/30659945 ID - 30659945 AB - Poster LA - English DB - MTMT ER - TY - CONF AU - Baka, J AU - Huzian, O AU - Duman, RS AU - Hajszán, Tibor TI - Remodeling of hippocampal spine synapses in a rat pseudopregnancy model of postpartum depression T2 - Clinical Neuroscience / Ideggyógyászati Szemle PY - 2012 SP - 7 PG - 1 UR - https://m2.mtmt.hu/api/publication/30659909 ID - 30659909 AB - Poster LA - English DB - MTMT ER - TY - CONF AU - Hajszán, Tibor TI - Disappearing synapses in major depressive disorder T2 - Clinical Neuroscience / Ideggyógyászati Szemle PY - 2012 SP - 26 EP - 27 PG - 1 UR - https://m2.mtmt.hu/api/publication/30645159 ID - 30645159 AB - Invited Lecture LA - English DB - MTMT ER - TY - GEN AU - Baka, Judith AU - Huzián, Orsolya AU - Duman, RS AU - Hajszán, Tibor TI - Remodeling of hippocampal spine synapses in a rat pseudopregnancy model of postpartum depression PY - 2012 UR - https://m2.mtmt.hu/api/publication/30645062 ID - 30645062 AB - Poster LA - English DB - MTMT ER -