Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis
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Citações na Scopus
4
Tipo de produção
article
Data de publicação
2023
Título da Revista
ISSN da Revista
Título do Volume
Editora
OXFORD UNIV PRESS
Autores
FALKAI, Peter
ROSSNER, Moritz J.
RAABE, Florian J.
WAGNER, Elias
KEESER, Daniel
MAURUS, Isabel
ROELL, Lukas
CHANG, Emily
SEITZ-HOLLAND, Johanna
SCHULZE, Thomas G.
Citação
SCHIZOPHRENIA BULLETIN, v.49, n.6, p.1614-1624, 2023
Resumo
Background and Hypothesis Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia. Study Design Here, we hypothesize that in schizophrenia, deficient maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes substantially contributes to abnormal frontotemporal macro- and micro-connectivity and subsequent cognitive deficits. Study Results Our postmortem studies indicate a reduced oligodendrocyte number in the cornu ammonis 4 (CA4) subregion of the hippocampus, and others have reported the same histopathological finding in the dorsolateral prefrontal cortex. Our series of studies on aerobic exercise training showed a volume increase in the hippocampus, specifically in the CA4 region, and improved cognition in individuals with schizophrenia. The cognitive effects were subsequently confirmed by meta-analyses. Cell-specific schizophrenia polygenic risk scores showed that exercise-induced CA4 volume increase significantly correlates with OPCs. From animal models, it is evident that early life stress and oligodendrocyte-related gene variants lead to schizophrenia-related behavior, cognitive deficits, impaired oligodendrocyte maturation, and reduced myelin thickness. Conclusions Based on these findings, we propose that pro-myelinating drugs (e.g., the histamine blocker clemastine) combined with aerobic exercise training may foster the regeneration of myelin plasticity as a basis for restoring frontotemporal connectivity and cognition in schizophrenia.
Palavras-chave
oligodendrocytes, oligodendrocyte precursor cells, myelination, cognition, hippocampus, prefrontal cortex
Referências
- AKBARIAN S, 1995, CEREB CORTEX, V5, P550, DOI 10.1093/cercor/5.6.550
- Assaf Y, 2008, J MOL NEUROSCI, V34, P51, DOI 10.1007/s12031-007-0029-0
- Badowska DM, 2020, TRANSL PSYCHIAT, V10, DOI 10.1038/s41398-020-01026-7
- Bähner F, 2017, EUR NEUROPSYCHOPHARM, V27, P93, DOI 10.1016/j.euroneuro.2016.12.007
- Basser PJ, 2002, NMR BIOMED, V15, P456, DOI 10.1002/nbm.783
- Bonoldi I, 2013, PSYCHIAT RES, V210, P8, DOI 10.1016/j.psychres.2013.05.003
- Bredin SSD, 2022, FRONT CARDIOVASC MED, V8, DOI 10.3389/fcvm.2021.753117
- Brzózka MM, 2010, BIOL PSYCHIAT, V68, P33, DOI 10.1016/j.biopsych.2010.03.015
- Buchanan RW, 2010, SCHIZOPHRENIA BULL, V36, P71, DOI 10.1093/schbul/sbp116
- Cai SP, 2020, BEHAV BRAIN RES, V379, DOI 10.1016/j.bbr.2019.112392
- Cannon M, 2002, AM J PSYCHIAT, V159, P1080, DOI 10.1176/appi.ajp.159.7.1080
- Cella M, 2017, CLIN PSYCHOL REV, V52, P43, DOI 10.1016/j.cpr.2016.11.009
- Cetin-Karayumak S, 2020, MOL PSYCHIATR, V25, P3208, DOI 10.1038/s41380-019-0509-y
- Cunniffe N, 2021, J NEUROL NEUROSUR PS, V92, P295, DOI 10.1136/jnnp-2020-324286
- Deshmukh VA, 2013, NATURE, V502, P327, DOI 10.1038/nature12647
- Ehrlich M, 2017, P NATL ACAD SCI USA, V114, pE2243, DOI 10.1073/pnas.1614412114
- Ellison-Wright I, 2009, SCHIZOPHR RES, V108, P3, DOI 10.1016/j.schres.2008.11.021
- Falkai P, 2015, MOL PSYCHIATR, V20, P671, DOI 10.1038/mp.2015.35
- Falkai P, 2021, EUR ARCH PSY CLIN N, V271, P1201, DOI 10.1007/s00406-021-01282-8
- Falkai P, 2020, EUR ARCH PSY CLIN N, V270, P413, DOI 10.1007/s00406-019-01067-0
- Falkai P, 2016, SCHIZOPHRENIA BULL, V42, pS4, DOI 10.1093/schbul/sbv157
- Falkai P, 2016, FRONT CELL NEUROSCI, V10, DOI [10.3389/fncel.2016.00078, 10.3389/fncel.2010.00078]
- Fields RD, 2008, TRENDS NEUROSCI, V31, P361, DOI 10.1016/j.tins.2008.04.001
- Firth J, 2017, SCHIZOPHRENIA BULL, V43, P546, DOI 10.1093/schbul/sbw115
- Fünfschilling U, 2012, NATURE, V485, P517, DOI 10.1038/nature11007
- García-León JA, 2018, STEM CELL REP, V10, P655, DOI 10.1016/j.stemcr.2017.12.014
- Georgieva L, 2006, P NATL ACAD SCI USA, V103, P12469, DOI 10.1073/pnas.0603029103
- Goff DC, 2013, WORLD PSYCHIATRY, V12, P99, DOI 10.1002/wps.20026
- Goff DC, 2011, PHARMACOL BIOCHEM BE, V99, P245, DOI 10.1016/j.pbb.2010.11.009
- Goldman SA, 2015, DEVELOPMENT, V142, P3983, DOI 10.1242/dev.126409
- Green AJ, 2017, LANCET, V390, P2481, DOI 10.1016/S0140-6736(17)32346-2
- Gustavsson A, 2011, EUR NEUROPSYCHOPHARM, V21, P718, DOI 10.1016/j.euroneuro.2011.08.008
- Hafner H., 2003, Schizophrenia, V2nd, P101, DOI 10.1002/9780470987353.CH8
- Hakak Y, 2001, P NATL ACAD SCI USA, V98, P4746, DOI 10.1073/pnas.081071198
- Hall MH, 2014, AM J MED GENET B, V165, P9, DOI 10.1002/ajmg.b.32212
- Haroutunian V, 2007, INT J NEUROPSYCHOPH, V10, P565, DOI 10.1017/S1461145706007310
- Hasan A, 2012, WORLD J BIOL PSYCHIA, V13, P318, DOI 10.3109/15622975.2012.696143
- Hermoye L, 2006, NEUROIMAGE, V29, P493, DOI 10.1016/j.neuroimage.2005.08.017
- Hof PR, 2003, BIOL PSYCHIAT, V53, P1075, DOI 10.1016/S0006-3223(03)00237-3
- Hoff AL, 2005, SCHIZOPHR RES, V78, P27, DOI 10.1016/j.schres.2005.05.010
- Holleran L, 2020, AM J PSYCHIAT, V177, P537, DOI 10.1176/appi.ajp.2019.19030225
- Insel TR, 2012, NATURE, V483, P269, DOI 10.1038/483269a
- Jääskeläinen E, 2013, SCHIZOPHRENIA BULL, V39, P1296, DOI 10.1093/schbul/sbs130
- Jensen SK, 2018, CELL REP, V24, P3167, DOI 10.1016/j.celrep.2018.08.060
- Jirsaraie RJ, 2018, SCHIZOPHR RES, V201, P237, DOI 10.1016/j.schres.2018.06.017
- Kahn RS, 2013, JAMA PSYCHIAT, V70, P1107, DOI 10.1001/jamapsychiatry.2013.155
- Kalkstein S, 2010, CURR TOP BEHAV NEURO, V4, P373, DOI 10.1007/7854_2010_42
- Kelly SM, 2018, SCHIZOPHR RES, V195, P76, DOI 10.1016/j.schres.2017.09.037
- Khadimallah I, 2022, MOL PSYCHIATR, V27, P1192, DOI 10.1038/s41380-021-01313-9
- Letzen BS, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0010480
- Lewis DA, 2012, TRENDS NEUROSCI, V35, P57, DOI 10.1016/j.tins.2011.10.004
- Li ZF, 2015, NEUROSCI BULL, V31, P617, DOI 10.1007/s12264-015-1555-3
- Liu J, 2016, J NEUROSCI, V36, P957, DOI 10.1523/JNEUROSCI.3608-15.2016
- Makinodan M, 2012, SCIENCE, V337, P1357, DOI 10.1126/science.1220845
- Malchow B, 2016, SCHIZOPHR RES, V173, P182, DOI 10.1016/j.schres.2015.01.005
- Malchow B, 2015, J NEURAL TRANSM, V122, P1019, DOI 10.1007/s00702-014-1316-x
- Malchow B, 2015, SCHIZOPHRENIA BULL, V41, P847, DOI 10.1093/schbul/sbv020
- Martins-de-Souza D, 2021, WORLD J BIOL PSYCHIA, V22, P271, DOI 10.1080/15622975.2020.1789217
- Mauney SA, 2015, SCHIZOPHR RES, V169, P374, DOI 10.1016/j.schres.2015.10.042
- Maurus I, 2022, TRANSL PSYCHIAT, V12, DOI 10.1038/s41398-022-02155-x
- Maurus I, 2022, SCHIZOPHRENIA-UK, V8, DOI 10.1038/s41537-022-00269-1
- Maurus I, 2021, EUR ARCH PSY CLIN N, V271, P315, DOI 10.1007/s00406-020-01175-2
- McPhie DL, 2018, TRANSL PSYCHIAT, V8, DOI 10.1038/s41398-018-0284-6
- Mei F, 2014, NAT MED, V20, P954, DOI 10.1038/nm.3618
- Micheva KD, 2016, ELIFE, V5, DOI 10.7554/eLife.15784
- Miller DJ, 2012, P NATL ACAD SCI USA, V109, P16480, DOI 10.1073/pnas.1117943109
- Miron VE, 2011, BBA-MOL BASIS DIS, V1812, P184, DOI 10.1016/j.bbadis.2010.09.010
- Mitkus SN, 2008, SCHIZOPHR RES, V98, P129, DOI 10.1016/j.schres.2007.09.032
- Molina V, 2017, PROG NEURO-PSYCHOPH, V76, P107, DOI 10.1016/j.pnpbp.2017.03.001
- Motavaf M, 2021, FRONT CELL NEUROSCI, V15, DOI 10.3389/fncel.2021.764486
- Murray CJL, 2020, LANCET, V396, P1223, DOI [10.1016/S0140-6736(20)30752-2, 10.1016/S0140-6736(20)30925-9]
- Najm FJ, 2015, NATURE, V522, P216, DOI 10.1038/nature14335
- Nave KA, 2010, NATURE, V468, P244, DOI 10.1038/nature09614
- NICHOLSON AN, 1987, TRENDS PHARMACOL SCI, V8, P247, DOI 10.1016/0165-6147(87)90192-1
- OISHI R, 1994, N-S ARCH PHARMACOL, V349, P140
- Orduz D, 2015, ELIFE, V4, DOI 10.7554/eLife.06953
- Page NF, 2021, BIOL PSYCHIAT, V89, P896, DOI 10.1016/j.biopsych.2020.10.016
- Pajonk FG, 2010, ARCH GEN PSYCHIAT, V67, P133, DOI 10.1001/archgenpsychiatry.2009.193
- Papiol S, 2017, TRANSL PSYCHIAT, V7, DOI 10.1038/tp.2017.131
- Papiol S, 2019, TRANSL PSYCHIAT, V9, DOI 10.1038/s41398-019-0618-z
- Pardiñas AF, 2018, NAT GENET, V50, P381, DOI 10.1038/s41588-018-0059-2
- Popovic D, 2019, FRONT NEUROSCI-SWITZ, V13, DOI 10.3389/fnins.2019.00274
- Prata DP, 2013, HUM BRAIN MAPP, V34, P2025, DOI 10.1002/hbm.22045
- Quednow BB, 2014, CELL MOL LIFE SCI, V71, P2815, DOI 10.1007/s00018-013-1553-4
- Raabe FJ, 2022, CELLS-BASEL, V11, DOI 10.3390/cells11020241
- Raabe FJ, 2019, CELLS-BASEL, V8, DOI 10.3390/cells8121496
- Raabe FJ, 2018, NPJ SCHIZOPHR, V4, DOI 10.1038/s41537-018-0066-4
- Ripke S, 2014, NATURE, V511, P421, DOI 10.1038/nature13595
- Roell L, 2022, EUR ARCH PSY CLIN N, V272, P1253, DOI 10.1007/s00406-022-01411-x
- Rowe RG, 2019, NAT REV GENET, V20, P377, DOI 10.1038/s41576-019-0100-z
- Santarelli DM, 2019, GENOM PROTEOM BIOINF, V17, P623, DOI 10.1016/j.gpb.2019.10.003
- Schmitt A, 2023, J NEURAL TRANSM, V130, P195, DOI 10.1007/s00702-022-02567-5
- Schmitt A, 2022, CELLS-BASEL, V11, DOI 10.3390/cells11203242
- Schmitt A, 2019, EUR ARCH PSY CLIN N, V269, P371, DOI 10.1007/s00406-019-01019-8
- Schmitt A, 2014, FRONT NEUROSCI-SWITZ, V8, DOI 10.3389/fnins.2014.00019
- Schmitt A, 2011, EUR ARCH PSY CLIN N, V261, P150, DOI 10.1007/s00406-011-0242-2
- Schmitt A, 2009, ACTA NEUROPATHOL, V117, P395, DOI 10.1007/s00401-008-0430-y
- Sha ZQ, 2019, BIOL PSYCHIAT, V85, P379, DOI 10.1016/j.biopsych.2018.11.011
- Shannon C, 2011, SCHIZOPHRENIA BULL, V37, P531, DOI 10.1093/schbul/sbp096
- Shen SM, 2005, J CELL BIOL, V169, P577, DOI 10.1083/jcb.200412101
- Shimada T, 2022, PSYCHIAT RES, V314, DOI 10.1016/j.psychres.2022.114656
- Sigurdsson T, 2010, NATURE, V464, P763, DOI 10.1038/nature08855
- Singh B, 2021, J CHEM NEUROANAT, V118, DOI 10.1016/j.jchemneu.2021.102035
- Skene NG, 2018, NAT GENET, V50, P825, DOI 10.1038/s41588-018-0129-5
- Stedehouder J, 2017, CEREB CORTEX, V27, P5001, DOI 10.1093/cercor/bhx203
- Stedehouder J, 2017, MOL PSYCHIATR, V22, P4, DOI 10.1038/mp.2016.147
- Steullet P, 2017, MOL PSYCHIATR, V22, P936, DOI 10.1038/mp.2017.47
- Svatkova A, 2015, SCHIZOPHRENIA BULL, V41, P869, DOI 10.1093/schbul/sbv033
- Trubetskoy V, 2022, NATURE, V604, P502, DOI 10.1038/s41586-022-04434-5
- Uranova N, 2001, BRAIN RES BULL, V55, P597, DOI 10.1016/S0361-9230(01)00528-7
- Uranova NA, 2010, WORLD J BIOL PSYCHIA, V11, P567, DOI 10.3109/15622970903414188
- van Praag H, 2000, NAT REV NEUROSCI, V1, P191, DOI 10.1038/35044558
- Vargas T, 2018, SCHIZOPHRENIA BULL, V44, P1091, DOI 10.1093/schbul/sbx160
- Varty GB, 2006, BEHAV BRAIN RES, V169, P162, DOI 10.1016/j.bbr.2005.11.025
- Voineskos AN, 2013, JAMA PSYCHIAT, V70, P472, DOI 10.1001/jamapsychiatry.2013.786
- Volk DW, 2000, ARCH GEN PSYCHIAT, V57, P237, DOI 10.1001/archpsyc.57.3.237
- Volkmann P, 2021, FRONT BEHAV NEUROSCI, V14, DOI 10.3389/fnbeh.2020.618180
- Wang F, 2020, NAT NEUROSCI, V23, P481, DOI 10.1038/s41593-020-0588-8
- Wedel M, 2020, NUCLEIC ACIDS RES, V48, P4839, DOI 10.1093/nar/gkaa218
- Windrem MS, 2017, CELL STEM CELL, V21, P195, DOI 10.1016/j.stem.2017.06.012
- Wirgenes KV, 2012, TRANSL PSYCHIAT, V2, DOI 10.1038/tp.2012.39
- Wittchen HU, 2011, EUR NEUROPSYCHOPHARM, V21, P655, DOI 10.1016/j.euroneuro.2011.07.018
- Yamada S, 2022, EUR ARCH PSY CLIN N, V272, P957, DOI 10.1007/s00406-021-01363-8
- Yao L, 2013, PROG NEURO-PSYCHOPH, V45, P100, DOI 10.1016/j.pnpbp.2013.04.019
- Ye F, 2009, NAT NEUROSCI, V12, P829, DOI 10.1038/nn.2333
- Yue WH, 2011, NAT GENET, V43, P1228, DOI 10.1038/ng.979
- Zhang HC, 2023, NEUROSCI BIOBEHAV R, V146, DOI 10.1016/j.neubiorev.2023.105064