[en] Currently, the role of the neurotrophic factors BDNF and GDNF in maintaining the brain's resistance to the damaging effects of hypoxia and functional recovery of neural networks after exposure to damaging factors are actively studied. The assessment of the effect of an increase in the level of these neurotrophic factors in brain tissues using genetic engineering methods on the resistance of laboratory animals to hypoxia may pave the way for the future clinical use of neurotrophic factors BDNF and GDNF in the treatment of hypoxic damage. This study aimed to evaluate the antihypoxic and neuroprotective properties of BDNF and GDNF expression level increase using adeno-associated viral vectors in modeling hypoxia in vivo. To achieve overexpression of neurotrophic factors in the central nervous system's cells, viral constructs were injected into the brain ventricles of newborn male C57Bl6 (P0) mice. Acute hypobaric hypoxia was modeled on the 30th day after the injection of viral vectors. Survival, cognitive, and mnestic functions in the late post-hypoxic period were tested. Evaluation of growth and weight characteristics and the neurological status of animals showed that the overexpression of neurotrophic factors does not affect the development of mice. It was found that the use of adeno-associated viral vectors increased the survival rate of male mice under hypoxic conditions. The present study indicates that the neurotrophic factors' overexpression, induced by the specially developed viral constructs carrying the BDNF and GDNF genes, is a prospective neuroprotection method, increasing the survival rate of animals after hypoxic injury.
Gavrish, Maria S; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny
Urazov, Mark D; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny
Mishchenko, Tatiana A ; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny
Turubanova, Victoria D; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny
Epifanova, Ekaterina ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin,
Krut', Victoria G ; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny ; Scientific Center for Genetics and Life Sciences, Sirius University of Science
Babaev, Alexey A; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny
Vedunova, Maria V ; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny
Mitroshina, Elena V; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny
Language :
English
Title :
Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia.
Publication date :
27 August 2022
Journal title :
International Journal of Molecular Sciences
ISSN :
1661-6596
eISSN :
1422-0067
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Ch
Volume :
23
Issue :
17
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
project No. 0729-2020-0061/the Ministry of Science and Higher Education of the Russian Federation/
Arancibia S. Silhol M. Moulière F. Meffre J. Höllinger I. Maurice T. Tapia-Arancibia L. Protective Effect of BDNF against Beta-Amyloid Induced Neurotoxicity in Vitro and in Vivo in Rats Neurobiol. Dis. 2008 31 316 326 10.1016/j.nbd.2008.05.012
Liu Y. Wang S. Luo S. Li Z. Liang F. Zhu Y. Pei Z. Huang R. Intravenous PEP-1-GDNF Is Protective after Focal Cerebral Ischemia in Rats Neurosci. Lett. 2016 617 150 155 10.1016/j.neulet.2016.02.017
Mitroshina E. Mishchenko T. Usenko A. Epifanova E. Yarkov R. Gavrish M. Babaev A. Vedunova M. AAV-Syn-BDNF-EGFP Virus Construct Exerts Neuroprotective Action on the Hippocampal Neural Network during Hypoxia In Vitro Int. J. Mol. Sci. 2018 19 2295 10.3390/ijms19082295
Zhang X. Zhou Y. Li H. Wang R. Yang D. Li B. Fu J. Intravenous Administration of DPSCs and BDNF Improves Neurological Performance in Rats with Focal Cerebral Ischemia Int. J. Mol. Med. 2018 41 3185 3194 10.3892/ijmm.2018.3517
Kim J.-Y. Ash R.T. Ceballos-Diaz C. Levites Y. Golde T.E. Smirnakis S.M. Jankowsky J.L. Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualising and manipulating neuronal circuits in vivo Eur. J. Neurosci. 2013 37 1203 1220 10.1111/ejn.12126
Kim J.-Y. Grunke S.D. Levites Y. Golde T.E. Jankowsky J.L. Intracerebroventricular Viral Injection of the Neonatal Mouse Brain for Persistent and Widespread Neuronal Transduction J. Vis. Exp. 2014 91 e51863 10.3791/51863
Snyder R.O. Flotte T.R. Production of Clinical-Grade Recombinant Adeno-Associated Virus Vectors Curr. Opin. Biotechnol. 2002 13 418 423 10.1016/S0958-1669(02)00369-5
Turovskaya M.V. Gaidin S.G. Vedunova M.V. Babaev A.A. Turovsky E.A. BDNF Overexpression Enhances the Preconditioning Effect of Brief Episodes of Hypoxia, Promoting Survival of GABAergic Neurons Neurosci. Bull. 2020 36 733 760 10.1007/s12264-020-00480-z 32219700
Andsberg G. Kokaia Z. Klein R.L. Muzyczka N. Lindvall O. Mandel R.J. Neuropathological and Behavioral Consequences of Adeno-Associated Viral Vector-Mediated Continuous Intrastriatal Neurotrophin Delivery in a Focal Ischemia Model in Rats Neurobiol. Dis. 2002 9 187 204 10.1006/nbdi.2001.0456 11895371
Yu S.-J. Tseng K.-Y. Shen H. Harvey B.K. Airavaara M. Wang Y. Local Administration of AAV-BDNF to Subventricular Zone Induces Functional Recovery in Stroke Rats PLoS ONE 2013 8 e81750 10.1371/journal.pone.0081750
Sakurai M. Abe K. Hayashi T. Setoguchi Y. Yaginuma G. Meguro T. Tabayashi K. Adenovirus-Mediated Glial Cell Line–Derived Neurotrophic Factor Gene Delivery Reduces Motor Neuron Injury after Transient Spinal Cord Ischemia in Rabbits J. Thorac. Cardiovasc. Surg. 2000 120 1148 1157 10.1067/mtc.2000.111178 11088040
Fu X. Chen H. Zhang N. Li W. Fang M. Zhang H. Fang Y. Ding M. Overexpression of Brain-Derived Neurotrophic Factor in the Hippocampus Protects against Post-Stroke Depression Neural Regen. Res. 2015 10 1427 10.4103/1673-5374.165510
Arvidsson A. Kirik D. Lundberg C. Mandel R.J. Andsberg G. Kokaia Z. Lindvall O. Elevated GDNF Levels Following Viral Vector-Mediated Gene Transfer Can Increase Neuronal Death after Stroke in Rats Neurobiol. Dis. 2003 14 542 556 10.1016/j.nbd.2003.08.002
Gustafsson E. Andsberg G. Darsalia V. Mohapel P. Mandel R.J. Kirik D. Lindvall O. Kokaia Z. Anterograde Delivery of Brain-Derived Neurotrophic Factor to Striatum via Nigral Transduction of Recombinant Adeno-Associated Virus Increases Neuronal Death but Promotes Neurogenic Response Following Stroke Eur. J. Neurosci. 2003 17 2667 2678 10.1046/j.1460-9568.2003.02713.x
Vedunova M.V. Sakharnova T.A. Mitroshina E.V. Shishkina T.V. Astrakhanova T.A. Mukhina I.V. Antihypoxic and Neuroprotective Properties of BDNF and GDNF in vitro and in vivo Under Hypoxic Conditions Sovrem. Tehnol. V Med. 2014 6 38 47
Mishchenko T.A. Mitroshina E.V. Shishkina T.V. Astrakhanova T.A. Prokhorova M.V. Vedunova M.V. Applicability of Live Cell Imaging of mRNA Expression in Combination with Calcium Imaging for In Vitro Studies of Neural Network Activity Biol. Membr. 2018 35 104 113 10.1134/S1990747818020095
de Pins B. Cifuentes-Díaz C. Thamila Farah A. López-Molina L. Montalban E. Sancho-Balsells A. López A. Ginés S. Delgado-García J.M. Alberch J. et al. Conditional BDNF Delivery from Astrocytes Rescues Memory Deficits, Spine Density and Synaptic Properties in the 5xFAD Mouse Model of Alzheimer Disease J. Neurosci. 2019 39 2441 2458 10.1523/jneurosci.2121-18.2019 30700530
Berretta A. Tzeng Y.-C. Clarkson A.N. Post-Stroke Recovery: The Role of Activity-Dependent Release of Brain-Derived Neurotrophic Factor Expert Rev. Neurother. 2014 14 1335 1344 10.1586/14737175.2014.969242 25319267
Zhao H. Alam A. San C.-Y. Eguchi S. Chen Q. Lian Q. Ma D. Molecular Mechanisms of Brain-Derived Neurotrophic Factor in Neuro-Protection: Recent Developments Brain Res. 2017 1665 1 21 10.1016/j.brainres.2017.03.029 28396009
Duarte E.P. Curcio M. Canzoniero L.M. Duarte C.B. Neuroprotection by GDNF in the Ischemic Brain Growth Factors 2012 30 242 257 10.3109/08977194.2012.691478
Nasrolahi A. Mahmoudi J. Akbarzadeh A. Karimipour M. Sadigh-Eteghad S. Salehi R. Farhoudi M. Neurotrophic Factors Hold Promise for the Future of Parkinson’s Disease Treatment: Is There a Light at the End of the Tunnel? Rev. Neurosci. 2018 29 475 489 10.1515/revneuro-2017-0040
Huang W. Meng F. Cao J. Liu X. Zhang J. Li M. Neuroprotective Role of Exogenous Brain-Derived Neurotrophic Factor in Hypoxia–Hypoglycemia-Induced Hippocampal Neuron Injury via Regulating Trkb/MiR134 Signaling J. Mol. Neurosci. 2017 62 35 42 10.1007/s12031-017-0907-z
Aly A.E.-E. Harmon B.T. Padegimas L. Sesenoglu-Laird O. Cooper M.J. Waszczak B.L. Intranasal Delivery of PGDNF DNA Nanoparticles Provides Neuroprotection in the Rat 6-Hydroxydopamine Model of Parkinson’s Disease Mol. Neurobiol. 2018 56 688 701 10.1007/s12035-018-1109-6
Behl T. Kaur I. Kumar A. Mehta V. Zengin G. Arora S. Gene Therapy in the Management of Parkinson’s Disease: Potential of GDNF as a Promising Therapeutic Strategy Curr. Gene Ther. 2020 20 207 222 10.2174/1566523220999200817164051
Liao J. Chen C. Ahn E.H. Liu X. Li H. Edgington-Mitchell L.E. Lu Z. Ming S. Ye K. Targeting both BDNF/TrkB pathway and delta-secretase for treating Alzheimer’s disease Neuropharmacology 2021 197 108737 10.1016/j.neuropharm.2021.108737
Budni J. Bellettini-Santos T. Mina F. Garcez M.L. Zugno A.L. The Involvement of BDNF, NGF and GDNF in Aging and Alzheimer’s Disease Aging Dis. 2015 6 331 10.14336/ad.2015.0825
Ibáñez C.F. Andressoo J.-O. Biology of GDNF and Its Receptors—Relevance for Disorders of the Central Nervous System Neurobiol. Dis. 2017 97 80 89 10.1016/j.nbd.2016.01.021 26829643
Wei Z.Z. Zhang J.Y. Taylor T.M. Gu X. Zhao Y. Wei L. Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice J. Cereb. Blood Flow Metab. 2017 38 404 421 10.1177/0271678x17702669 28430000
Cheng J. Shen W. Jin L. Pan J. Zhou Y. Pan G. Xie Q. Hu Q. Wu S. Zhang H. et al. Treadmill exercise promotes neurogenesis and myelin repair via upregulating Wnt/β-catenin signaling pathways in the juvenile brain following focal cerebral ischemia/reperfusion Int. J. Mol. Med. 2020 45 1447 1463 10.3892/ijmm.2020.4515 32323740
Gaidin S.G. Turovskaya M.V. Gavrish M.S. Babaev A.A. Mal’tseva V.N. Blinova E.V. Turovsky E.A. The Selective BDNF Overexpression in Neurons Protects Neuroglial Networks against OGD and Glutamate-Induced Excitotoxicity Int. J. Neurosci. 2019 130 363 383 10.1080/00207454.2019.1691205 31694441
Mitroshina E.V. Yarkov R.S. Mishchenko T.A. Krut’ V.G. Gavrish M.S. Epifanova E.A. Babaev A.A. Vedunova M.V. Brain-Derived Neurotrophic Factor (BDNF) Preserves the Functional Integrity of Neural Networks in the β-Amyloidopathy Model In Vitro Front. Cell Dev. Biol. 2020 8 582 10.3389/fcell.2020.00582 32733889
Bratek-Gerej E. Ziembowicz A. Salinska E. Group II Metabotropic Glutamate Receptors Reduce Apoptosis and Regulate BDNF and GDNF Levels in Hypoxic-Ischemic Injury in Neonatal Rats Int. J. Mol. Sci. 2022 23 7000 10.3390/ijms23137000
Albert K. Voutilainen M. Domanskyi A. Airavaara M. AAV Vector-Mediated Gene Delivery to Substantia Nigra Dopamine Neurons: Implications for Gene Therapy and Disease Models Genes 2017 8 63 10.3390/genes8020063
Chen J. Zhang T. Jiao S. Zhou X. Zhong J. Wang Y. Liu J. Deng J. Wang S. Xu Z. ProBDNF Accelerates Brain Amyloid-β Deposition and Learning and Memory Impairment in APPswePS1dE9 Transgenic Mice J. Alzheimer’s Dis. 2017 59 941 949 10.3233/jad-161191
Stefani A. Pierantozzi M. Cardarelli S. Stefani L. Cerroni R. Conti M. Garasto E. Mercuri N.B. Marini C. Sucapane P. Neurotrophins as Therapeutic Agents for Parkinson’s Disease; New Chances from Focused Ultrasound? Front. Neurosci. 2022 16 846681 10.3389/fnins.2022.846681
Ozlu C. Bailey R.M. Sinnett S. Goodspeed K.D. Gene Transfer Therapy for Neurodevelopmental Disorders Dev. Neurosci. 2021 43 230 240 10.1159/000515434
Ahn S.Y. Sung D.K. Chang Y.S. Sung S.I. Kim Y.E. Kim H.-J. Lee S.M. Park W.S. BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury Int. J. Mol. Sci. 2021 22 11395 10.3390/ijms222111395 34768827
Xue L.-L. Du R.-L. Hu Y. Xiong L.-L. Su Z.-Y. Ma Z. Tan Y.-X. Liu J. Hu Q. Zhu Z.-Q. et al. BDNF Promotes Neuronal Survival after Neonatal Hypoxic-Ischemic Encephalopathy by up-Regulating Stx1b and Suppressing VDAC1 Brain Res. Bull. 2021 174 131 140 10.1016/j.brainresbull.2021.05.013 34058286
Markosyan V. Safiullov Z. Izmailov A. Fadeev F. Sokolov M. Kuznetsov M. Trofimov D. Kim E. Kundakchyan G. Gibadullin A. et al. Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat Int. J. Mol. Sci. 2020 21 6858 10.3390/ijms21186858
Beker M.Ç. Beker M. Çağlayan A.B. Bolat B. Kiliç Ü. Köse G. Kiliç E. Striatal Dopaminergic Neurons as a Potential Target for GDNF Based Ischemic Stroke Therapy Turk. J. Med. Sci. 2021 52 248 257 10.3906/sag-2108-268
Mishchenko T.A. Mitroshina E.V. Usenko A.V. Voronova N.V. Astrakhanova T.A. Shirokova O.M. Kastalskiy I.A. Vedunova M.V. Features of Neural Network Formation and Their Functions in Primary Hippocampal Cultures in the Context of Chronic TrkB Receptor System Influence Front. Physiol. 2019 9 1925 10.3389/fphys.2018.01925 30687128
Burtscher J. Mallet R.T. Burtscher M. Millet G.P. Hypoxia and Brain Aging: Neurodegeneration or Neuroprotection? Ageing Res. Rev. 2021 68 101343 10.1016/j.arr.2021.101343
Tarkowska A. Hypoxic-Ischemic Brain Injury after Perinatal Asphyxia as a Possible Factor in the Pathology of Alzheimer’s Disease Cerebral Ischemia Exon Publications Brisbane City, Australia 2021 45 60 10.36255/exonpublications.cerebralischemia.2021.perinatalasphyxia
Nieuwenhuis B. Haenzi B. Hilton S. Carnicer-Lombarte A. Hobo B. Verhaagen J. Fawcett J.W. Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: Comparison of four promoters Gene Ther. 2021 28 56 74 10.1038/s41434-020-0169-1
Mao Y. Wang X. Yan R. Hu W. Li A. Wang S. Li H. Single point mutation in adeno-associated viral vectors -DJ capsid leads to improvement for gene delivery in vivo BMC Biotechnol. 2016 6 1 10.1186/s12896-015-0230-0
Zhang Z. Stickney Z. Duong N. Curley K. Lu B. AAV-Based Dual-Reporter Circuit for Monitoring Cell Signaling in Living Human Cells J. Biol. Eng. 2017 11 18 10.1186/s13036-017-0060-9
Lu Y. Recombinant Adeno-Associated Virus As Delivery Vector for Gene Therapy—A Review Stem Cells Dev. 2004 13 133 145 10.1089/154732804773099335
Passini M.A. Watson D.J. Vite C.H. Landsburg D.J. Feigenbaum A.L. Wolfe J.H. Intraventricular Brain Injection of Adeno-Associated Virus Type 1 (AAV1) in Neonatal Mice Results in Complementary Patterns of Neuronal Transduction to AAV2 and Total Long-Term Correction of Storage Lesions in the Brains of β-Glucuronidase-Deficient Mice J. Virol. 2003 77 7034 7040 10.1128/jvi.77.12.7034-7040.2003 12768022
Passini M.A. Wolfe J.H. Widespread Gene Delivery and Structure-Specific Patterns of Expression in the Brain after Intraventricular Injections of Neonatal Mice with an Adeno-Associated Virus Vector J. Virol. 2001 75 12382 12392 10.1128/jvi.75.24.12382-12392.2001 11711628
de Jonge H.J.M. Fehrmann R.S.N. de Bont E.S.J.M. Hofstra R.M.W. Gerbens F. Kamps W.A. de Vries E.G.E. van der Zee A.G.J. te Meerman G.J. ter Elst A. Evidence Based Selection of Housekeeping Genes PLoS ONE 2007 2 e898 10.1371/journal.pone.0000898
Kuster G.W. Baruzzi A.C. de Paula Pacheco E. Domingues R.B. Pieruccetti M. Giacon L.M.T. Garcia J.C.T. Furlan V. Massaro A.R. Early reperfusion therapy in acute ischemic stroke after recent myocardial infarction Arq. Neuro-Psiquiatr. 2016 74 690 691 10.1590/0004-282X20160099
Luk’yanova L.D. Guidelines on Experimental Study of Drugs Offered for Clinical Study as Antihypoxic Agents Publishing house of the USSR Ministry of Health Moscow, Russia 1990
Prevot V. Puberty in Mice and Rats Knobil and Neill’s Physiology of Reproduction 4th ed. Chapter 30 Academic Press Cambridge, MA, USA 2015
Roa J. Ruiz-Cruz M. Ruiz-Pino F. Onieva R. Vazquez M.J. Sanchez-Tapia M.J. Ruiz-Rodriguez J.M. Sobrino V. Barroso A. Heras V. et al. Dicer Ablation in Kiss1 Neurons Impairs Puberty and Fertility Preferentially in Female Mice Nat. Commun. 2022 13 4663 10.1038/s41467-022-32347-4
Guo X. Tian Y. Yang Y. Li S. Guo L. Shi J. Pituitary Adenylate Cyclase-Activating Polypeptide Protects Against Cognitive Impairment Caused by Chronic Cerebral Hypoperfusion Mol. Neurobiol. 2021 58 4309 4322 10.1007/s12035-021-02381-2
Wang J. Zhang S. Ma H. Yang S. Liu Z. Wu X. Wang S. Zhang Y. Liu Y. Chronic Intermittent Hypobaric Hypoxia Pretreatment Ameliorates Ischemia-Induced Cognitive Dysfunction Through Activation of ERK1/2-CREB-BDNF Pathway in Anesthetized Mice Neurochem. Res. 2016 42 501 512 10.1007/s11064-016-2097-4
Shang Y. Yan Y. Chen B. Zhang J. Zhang T. Over-expressed MST1 Impaired Spatial Memory via Disturbing Neural Oscillation Patterns in Mice Genes Brain Behav. 2020 19 e12678 10.1111/gbb.12678
D’Hooge R. De Deyn P.P. Applications of the Morris Water Maze in the Study of Learning and Memory Brain Res. Rev. 2001 36 60 90 10.1016/s0165-0173(01)00067-4
