title: Pathological brain plasticity and cognition in the offspring of males subjected to postnatal traumatic stress.
abstract: Traumatic stress in early-life increases the risk for cognitive and neuropsychiatric disorders later in life. Such early stress can also impact the progeny even if not directly exposed, likely through epigenetic mechanisms. Here, we report in mice that the offspring of males subjected to postnatal traumatic stress have decreased gene expression in molecular pathways necessary for neuronal signaling, and altered synaptic plasticity when adult. Long-term potentiation is abolished and long-term depression is enhanced in the hippocampus, and these defects are associated with impaired long-term memory in both the exposed fathers and their offspring. The brain-specific gamma isoform of protein kinase C (Prkcc) is one of the affected signaling components in the hippocampus. Its expression is reduced in the offspring, and DNA methylation at its promoter is altered both in the hippocampus of the offspring and the sperm of fathers. These results suggest that postnatal traumatic stress in males can affect brain plasticity and cognitive functions in the adult progeny, possibly through epigenetic alterations in the male germline.
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Bohacek
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Farinelli
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Mirante
authors.affiliation: Pharma Division, Hoffmann-La Roche, Basel, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Steiner
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Gapp
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Coiret
authors.affiliation: Pharma Division, Hoffmann-La Roche, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Ebeling
authors.affiliation: Pharma Division, Hoffmann-La Roche, Basel, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Durán-Pacheco
authors.affiliation: Roche NimbleGen, Inc., Madison, WI, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Iniguez
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Manuella
authors.affiliation: Pharma Division, Hoffmann-La Roche, Basel, Switzerland.
authors.forename: J-L
authors.initials: JL
authors.lastname: Moreau
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: I M
authors.initials: IM
authors.lastname: Mansuy
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D003213:Conditioning, Psychological; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005239:Fear / Q000523:psychology; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology; D040921:Stress Disorders, Traumatic / Q000150:complications* / Q000473:pathology*; D013550:Swimming / Q000523:psychology
chemical_list: C087857:protein kinase C gamma; D011493:Protein Kinase C
references.citation: Behav Brain Res. 2014 May 15;265:32-7
references.pmid: 24556204
references.citation: J Neurosci. 1982 Jan;2(1):32-48
references.pmid: 7054394
references.citation: Brief Bioinform. 2008 May;9(3):189-97
references.pmid: 18202032
references.citation: Nat Neurosci. 2014 May;17(5):667-9
references.pmid: 24728267
references.citation: Psychol Med. 2008 Jun;38(6):771-85
references.pmid: 17922938
references.citation: Ann N Y Acad Sci. 2010 Feb;1186:190-222
references.pmid: 20201874
references.citation: Nature. 1997 May 29;387(6632):497-500
references.pmid: 9168111
references.citation: PLoS Med. 2012;9(11):e1001349
references.pmid: 23209385
references.citation: Nat Neurosci. 2013 Jan;16(1):42-7
references.pmid: 23242310
references.citation: Proc Natl Acad Sci U S A. 1996 May 14;93(10):4750-3
references.pmid: 8643474
references.citation: J Biol Chem. 1990 Nov 15;265(32):19961-5
references.pmid: 2246272
references.citation: J Am Assoc Lab Anim Sci. 2011 Sep;50(5):641-6
references.pmid: 22330709
references.citation: J Neurosci. 2005 Apr 27;25(17):4288-93
references.pmid: 15858055
references.citation: Brain Res. 2006 Jul 12;1099(1):101-8
references.pmid: 16784730
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W71-4
references.pmid: 17485472
references.citation: Nat Rev Neurosci. 2011 Sep 07;12(10):585-601
references.pmid: 21897434
references.citation: Nature. 2002 Aug 29;418(6901):970-5
references.pmid: 12198546
references.citation: Nat Rev Neurosci. 2002 Jun;3(6):453-62
references.pmid: 12042880
references.citation: Biol Psychiatry. 2013 Feb 15;73(4):313-20
references.pmid: 23062885
references.citation: J Neurophysiol. 2007 Dec;98(6):3688-95
references.pmid: 17913995
references.citation: Nat Neurosci. 2009 Dec;12(12):1559-66
references.pmid: 19898468
references.citation: Hum Genet. 2009 Jul;126(1):215-32
references.pmid: 19294424
references.citation: Biol Psychiatry. 2013 Jan 1;73(1):44-53
references.pmid: 22906514
references.citation: Psychoneuroendocrinology. 2007 Apr;32(3):256-66
references.pmid: 17307298
references.citation: Swiss Med Wkly. 2011 Jan 20;140:w13123
references.pmid: 21253921
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15023-7
references.pmid: 17848509
references.citation: Psychopharmacology (Berl). 2011 Mar;214(1):55-70
references.pmid: 20865251
references.citation: PLoS One. 2010 Sep 30;5(9):
references.pmid: 20927350
references.citation: Cell. 1993 Dec 31;75(7):1253-62
references.pmid: 8269509
references.citation: Mol Psychiatry. 2011 Oct;16(10):996-1005
references.pmid: 21826061
references.citation: Neuropsychopharmacology. 2013 Jan;38(1):220-36
references.pmid: 22781843
references.citation: J Neurosci. 2007 Jul 18;27(29):7648-53
references.pmid: 17634359
references.citation: Ann Anat. 2010 Sep 20;192(5):275-83
references.pmid: 20810260
references.citation: Cell. 2010 Dec 23;143(7):1084-96
references.pmid: 21183072
references.citation: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4363-7
references.pmid: 1350090
references.citation: Cell. 1993 Dec 31;75(7):1263-71
references.pmid: 8269510
references.citation: Horm Behav. 2011 Mar;59(3):290-5
references.pmid: 20483359
references.citation: PLoS One. 2011;6(7):e21842
references.pmid: 21799751
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D685-90
references.pmid: 21071392
references.citation: Int J Neuropsychopharmacol. 2009 May;12(4):553-9
references.pmid: 18976544
references.citation: Nat Rev Genet. 2007 Apr;8(4):253-62
references.pmid: 17363974
references.citation: Nat Rev Neurosci. 2009 Jun;10(6):434-45
references.pmid: 19401723
references.citation: Am Psychol. 2012 Feb-Mar;67(2):130-59
references.pmid: 22233090
references.citation: Biol Psychiatry. 2010 Sep 1;68(5):408-15
references.pmid: 20673872
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: Neuropsychology. 2010 Jan;24(1):9-34
references.pmid: 20063944
references.citation: FEBS Lett. 1995 Jul 17;368(2):276-8
references.pmid: 7628620
references.citation: Endocrinology. 2012 Aug;153(8):3828-38
references.pmid: 22707478
references.citation: Dialogues Clin Neurosci. 2011;13(3):360-5
references.pmid: 22033827
references.citation: J Neurosci. 1994 Sep;14(9):5325-37
references.pmid: 7916043
references.citation: J Neurosci. 2009 Feb 4;29(5):1496-502
references.pmid: 19193896
references.citation: Front Behav Neurosci. 2011 Feb 04;5:3
references.pmid: 21331159
references.citation: Dev Psychobiol. 2010 May;52(4):312-30
references.pmid: 20373326
references.citation: Nat Rev Neurosci. 2012 Feb 15;13(3):169-82
references.pmid: 22334212
references.citation: Endocrinology. 2011 Jun;152(6):2228-36
references.pmid: 21447631
references.citation: Science. 2001 Nov 2;294(5544):1030-8
references.pmid: 11691980
references.citation: Psychopharmacology (Berl). 2011 Mar;214(1):121-30
references.pmid: 21107538
references.citation: Mol Psychiatry. 2002;7(6):609-16
references.pmid: 12140784
references.citation: J Psychiatr Res. 2012 Apr;46(4):500-6
references.pmid: 22336639
references.citation: Z Psychosom Med Psychother. 2002;48(4):370-80
references.pmid: 12407495
references.citation: Biol Psychiatry. 2011 Sep 1;70(5):408-14
references.pmid: 21679926
references.citation: J Neurosci. 2010 Sep 29;30(39):13005-15
references.pmid: 20881118
references.citation: J Neurosci. 2006 Feb 8;26(6):1721-9
references.pmid: 16467520
references.citation: Biochim Biophys Acta. 2010 Oct;1800(10):1068-76
references.pmid: 20100548
references.citation: Lancet. 2009 Jan 3;373(9657):68-81
references.pmid: 19056114
references.citation: Bioessays. 2014 May;36(5):491-502
references.pmid: 24585414
references.citation: BMC Bioinformatics. 2008 Nov 01;9:465
references.pmid: 18976492
references.citation: Nature. 2009 Oct 8;461(7265):747-53
references.pmid: 19812666
references.citation: Eur J Neurosci. 2006 Jan;23(1):261-72
references.pmid: 16420435
references.citation: Mol Psychiatry. 2014 Nov;19(11):1171-8
references.pmid: 24342991
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: J Neurosci. 2011 Sep 21;31(38):13625-34
references.pmid: 21940453
references.citation: J Neurosci. 2011 Aug 17;31(33):11748-55
references.pmid: 21849535
references.citation: Mol Psychiatry. 2013 Mar;18(3):320-31
references.pmid: 22371048
references.citation: Learn Mem. 1994 May-Jun;1(1):74-82
references.pmid: 10467587
references.citation: Nature. 2003 Dec 18;426(6968):841-5
references.pmid: 14685239
references.citation: J Neurosci. 2013 May 22;33(21):9003-12
references.pmid: 23699511