Top

Published in:

Open Access 01-12-2023 | Cytokines | Research

Neonatal inflammation increases hippocampal KCC2 expression through methylation-mediated TGF-β1 downregulation leading to impaired hippocampal cognitive function and synaptic plasticity in adult mice

Authors: Jing Rong, Yang Yang, Min Liang, Haiquan Zhong, Yingchun Li, Yichao Zhu, Sha Sha, Lei Chen, Rong Zhou

Published in: Journal of Neuroinflammation | Issue 1/2023

Abstract

The mechanisms by which neonatal inflammation leads to cognitive deficits in adulthood remain poorly understood. Inhibitory GABAergic synaptic transmission plays a vital role in controlling learning, memory and synaptic plasticity. Since early-life inflammation has been reported to adversely affect the GABAergic synaptic transmission, the aim of this study was to investigate whether and how neonatal inflammation affects GABAergic synaptic transmission resulting in cognitive impairment. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 μg/kg) or saline on postnatal days 3–5. It was found that blocking GABAergic synaptic transmission reversed the deficit in hippocampus-dependent memory or the induction failure of long-term potentiation in the dorsal CA1 in adult LPS mice. An increase of mIPSCs amplitude was further detected in adult LPS mice indicative of postsynaptic potentiation of GABAergic transmission. Additionally, neonatal LPS resulted in the increased expression and function of K⁺–Cl⁻-cotransporter 2 (KCC2) and the decreased expression of transforming growth factor-beta 1 (TGF-β1) in the dorsal CA1 during adulthood. The local TGF-β1 overexpression improved KCC2 expression and function, synaptic plasticity and memory of adult LPS mice. Adult LPS mice show hypermethylation of TGFb1 promoter and negatively correlate with reduced TGF-β1 transcripts. 5-Aza-deoxycytidine restored the changes in TGFb1 promoter methylation and TGF-β1 expression. Altogether, the results suggest that hypermethylation-induced reduction of TGF-β1 leads to enhanced GABAergic synaptic inhibition through increased KCC2 expression, which is a underlying mechanism of neonatal inflammation-induced hippocampus-dependent memory impairment in adult mice.

Available only for authorised users

Bilbo SD, Biedenkapp JC, Der-Avakian A, Watkins LR, Rudy JW, Maier SF. Neonatal infection-induced memory impairment after lipopolysaccharide in adulthood is prevented via caspase-1 inhibition. J Neurosci. 2005;25(35):8000–9. https://doi.org/10.1523/jneurosci.1748-05.2005.CrossRef

Oldenburg KS, O’Shea TM, Fry RC. Genetic and epigenetic factors and early life inflammation as predictors of neurodevelopmental outcomes. Semin Fetal Neonatal Med. 2020;25(3):101115. https://doi.org/10.1016/j.siny.2020.101115.CrossRef

Shanks N, Windle RJ, Perks PA, Harbuz MS, Jessop DS, Ingram CD, Lightman SL. Early-life exposure to endotoxin alters hypothalamic-pituitary-adrenal function and predisposition to inflammation. Proc Natl Acad Sci USA. 2000;97(10):5645–50. https://doi.org/10.1073/pnas.090571897.CrossRef

Doenni VM, Gray JM, Song CM, Patel S, Hill MN, Pittman QJ. Deficient adolescent social behavior following early-life inflammation is ameliorated by augmentation of anandamide signaling. Brain Behav Immun. 2016;58:237–47. https://doi.org/10.1016/j.bbi.2016.07.152.CrossRef

Canetta S, Sourander A, Surcel HM, Hinkka-Yli-Salomäki S, Leiviskä J, Kellendonk C, McKeague IW, Brown AS. Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort. Am J Psychiatry. 2014;171(9):960–8. https://doi.org/10.1176/appi.ajp.2014.13121579.CrossRef

Brown AS, Sourander A, Hinkka-Yli-Salomäki S, McKeague IW, Sundvall J, Surcel HM. Elevated maternal C-reactive protein and autism in a national birth cohort. Mol Psychiatry. 2014;19(2):259–64. https://doi.org/10.1038/mp.2012.197.CrossRef

Bilbo SD, Block CL, Bolton JL, Hanamsagar R, Tran PK. Beyond infection—maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders. Exp Neurol. 2018;299(Pt A):241–51. https://doi.org/10.1016/j.expneurol.2017.07.002.CrossRef

Parboosing R, Bao Y, Shen L, Schaefer CA, Brown AS. Gestational influenza and bipolar disorder in adult offspring. JAMA Psychiat. 2013;70(7):677–85. https://doi.org/10.1001/jamapsychiatry.2013.896.CrossRef

Baghel MS, Singh B, Patro N, Khanna VK, Patro IK, Thakur MK. Poly (I:C) Exposure in early life alters methylation of dna and acetylation of histone at synaptic plasticity gene promoter in developing rat brain leading to memory impairment. Ann Neurosci. 2019;26(3–4):35–41. https://doi.org/10.1177/0972753120919704.CrossRef

10.

Labrousse VF, Leyrolle Q, Amadieu C, Aubert A, Sere A, Coutureau E, Grégoire S, Bretillon L, Pallet V, Gressens P, Joffre C, Nadjar A, Layé S. Dietary omega-3 deficiency exacerbates inflammation and reveals spatial memory deficits in mice exposed to lipopolysaccharide during gestation. Brain Behav Immun. 2018;73:427–40. https://doi.org/10.1016/j.bbi.2018.06.004.CrossRef

11.

Liang M, Zhong H, Rong J, Li Y, Zhu C, Zhou L, Zhou R. Postnatal lipopolysaccharide exposure impairs adult neurogenesis and causes depression-like behaviors through astrocytes activation triggering GABAA receptor downregulation. Neuroscience. 2019;422:21–31. https://doi.org/10.1016/j.neuroscience.2019.10.025.CrossRef

12.

Nouel D, Burt M, Zhang Y, Harvey L, Boksa P. Prenatal exposure to bacterial endotoxin reduces the number of GAD67- and reelin-immunoreactive neurons in the hippocampus of rat offspring. Eur Neuropsychopharmacol. 2012;22(4):300–7. https://doi.org/10.1016/j.euroneuro.2011.08.001.CrossRef

13.

Harvey L, Boksa P. A stereological comparison of GAD67 and reelin expression in the hippocampal stratum oriens of offspring from two mouse models of maternal inflammation during pregnancy. Neuropharmacology. 2012;62(4):1767–76. https://doi.org/10.1016/j.neuropharm.2011.11.022.CrossRef

14.

Nyffeler M, Meyer U, Yee BK, Feldon J, Knuesel I. Maternal immune activation during pregnancy increases limbic GABAA receptor immunoreactivity in the adult offspring: implications for schizophrenia. Neuroscience. 2006;143(1):51–62. https://doi.org/10.1016/j.neuroscience.2006.07.029.CrossRef

15.

Collinson N, Kuenzi FM, Jarolimek W, Maubach KA, Cothliff R, Sur C, Smith A, Otu FM, Howell O, Atack JR, McKernan RM, Seabrook GR, Dawson GR, Whiting PJ, Rosahl TW. Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABAA receptor. J Neurosci. 2002;22(13):5572–80. https://doi.org/10.1523/jneurosci.22-13-05572.2002.CrossRef

16.

Kolasinski J, Hinson EL, Divanbeighi Zand AP, Rizov A, Emir UE, Stagg CJ. The dynamics of cortical GABA in human motor learning. J Physiol. 2019;597(1):271–82. https://doi.org/10.1113/jp276626.CrossRef

17.

Jie F, Yin G, Yang W, Yang M, Gao S, Lv J, Li B. Stress in regulation of GABA amygdala system and relevance to neuropsychiatric diseases. Front Neurosci. 2018;12:562. https://doi.org/10.3389/fnins.2018.00562.CrossRef

18.

Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, Neul JL, Gong S, Lu HC, Heintz N, Ekker M, Rubenstein JL, Noebels JL, Rosenmund C, Zoghbi HY. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature. 2010;468(7321):263–9. https://doi.org/10.1038/nature09582.CrossRef

19.

Kaila K, Ruusuvuori E, Seja P, Voipio J, Puskarjov M. GABA actions and ionic plasticity in epilepsy. Curr Opin Neurobiol. 2014;26:34–41. https://doi.org/10.1016/j.conb.2013.11.004.CrossRef

20.

Glausier JR, Lewis DA. GABA and schizophrenia: where we stand and where we need to go. Schizophr Res. 2017;181:2–3. https://doi.org/10.1016/j.schres.2017.01.050.CrossRef

21.

Di J, Li J, O’Hara B, Alberts I, Xiong L, Li J, Li X. The role of GABAergic neural circuits in the pathogenesis of autism spectrum disorder. Int J Dev Neurosci. 2020;80(2):73–85. https://doi.org/10.1002/jdn.10005.CrossRef

22.

Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16(4):383–406. https://doi.org/10.1038/mp.2010.120.CrossRef

23.

Kleschevnikov AM, Belichenko PV, Gall J, George L, Nosheny R, Maloney MT, Salehi A, Mobley WC. Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis. 2012;45(2):683–91. https://doi.org/10.1016/j.nbd.2011.10.009.CrossRef

24.

Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ. Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell. 2008;135(3):549–60. https://doi.org/10.1016/j.cell.2008.09.060.CrossRef

25.

Türkmen S, Löfgren M, Birzniece V, Bäckström T, Johansson IM. Tolerance development to Morris water maze test impairments induced by acute allopregnanolone. Neuroscience. 2006;139(2):651–9. https://doi.org/10.1016/j.neuroscience.2005.12.031.CrossRef

26.

Mtchedlishvili Z, Lepsveridze E, Xu H, Kharlamov EA, Lu B, Kelly KM. Increase of GABAA receptor-mediated tonic inhibition in dentate granule cells after traumatic brain injury. Neurobiol Dis. 2010;38(3):464–75. https://doi.org/10.1016/j.nbd.2010.03.012.CrossRef

27.

Silvers JM, Tokunaga S, Berry RB, White AM, Matthews DB. Impairments in spatial learning and memory: ethanol, allopregnanolone, and the hippocampus. Brain Res Brain Res Rev. 2003;43(3):275–84. https://doi.org/10.1016/j.brainresrev.2003.09.002.CrossRef

28.

Martínez-Cué C, Martínez P, Rueda N, Vidal R, García S, Vidal V, Corrales A, Montero JA, Pazos Á, Flórez J, Gasser R, Thomas AW, Honer M, Knoflach F, Trejo JL, Wettstein JG, Hernández MC. Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome. J Neurosci. 2013;33(9):3953–66. https://doi.org/10.1523/jneurosci.1203-12.2013.CrossRef

29.

Na ES, Morris MJ, Nelson ED, Monteggia LM. GABAA receptor antagonism ameliorates behavioral and synaptic impairments associated with MeCP2 overexpression. Neuropsychopharmacology. 2014;39(8):1946–54. https://doi.org/10.1038/npp.2014.43.CrossRef

30.

Estes ML, McAllister AK. Maternal immune activation: Implications for neuropsychiatric disorders. Science. 2016;353(6301):772–7. https://doi.org/10.1126/science.aag3194.CrossRef

31.

Jung YH, Shin NY, Jang JH, Lee WJ, Lee D, Choi Y, Choi SH, Kang DH. Relationships among stress, emotional intelligence, cognitive intelligence, and cytokines. Medicine. 2019;98(18):e15345. https://doi.org/10.1097/md.0000000000015345.CrossRef

32.

Comim CM, Bussmann RM, Simão SR, Ventura L, Freiberger V, Patrício JJ, Palmas D, Mendonça BP, Cassol OJ Jr, Quevedo J. Experimental neonatal sepsis causes long-term cognitive impairment. Mol Neurobiol. 2016;53(9):5928–34. https://doi.org/10.1007/s12035-015-9495-5.CrossRef

33.

Wei H, Chadman KK, McCloskey DP, Sheikh AM, Malik M, Brown WT, Li X. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta. 2012;1822(6):831–42. https://doi.org/10.1016/j.bbadis.2012.01.011.CrossRef

34.

Chen J, Song Y, Yang J, Zhang Y, Zhao P, Zhu XJ, Su HC. The contribution of TNF-α in the amygdala to anxiety in mice with persistent inflammatory pain. Neurosci Lett. 2013;541:275–80. https://doi.org/10.1016/j.neulet.2013.02.005.CrossRef

35.

Chiu GS, Darmody PT, Walsh JP, Moon ML, Kwakwa KA, Bray JK, McCusker RH, Freund GG. Adenosine through the A2A adenosine receptor increases IL-1β in the brain contributing to anxiety. Brain Behav Immun. 2014;41:218–31. https://doi.org/10.1016/j.bbi.2014.05.018.CrossRef

36.

Li LY, Li JL, Zhang HM, Yang WM, Wang K, Fang Y, Wang Y. TGFβ1 treatment reduces hippocampal damage, spontaneous recurrent seizures, and learning memory deficits in pilocarpine-treated rats. J Mol Neurosci. 2013;50(1):109–23. https://doi.org/10.1007/s12031-012-9879-1.CrossRef

37.

Bahramabadi R, Fathollahi MS, Hashemi SM, Arababadi AS, Arababadi MS, Yousefi-Daredor H, Bidaki R, Khaleghinia M, Bakhshi MH, Yousefpoor Y, Torbaghan YE, Arababadi MK. Serum levels of IL-6, IL-8, TNF-α, and TGF-β in chronic HBV-infected patients: effect of depression and anxiety. Lab Med. 2017;49(1):41–6. https://doi.org/10.1093/labmed/lmx064.CrossRef

38.

Depino AM, Lucchina L, Pitossi F. Early and adult hippocampal TGF-β1 overexpression have opposite effects on behavior. Brain Behav Immun. 2011;25(8):1582–91. https://doi.org/10.1016/j.bbi.2011.05.007.CrossRef

39.

Chen YH, Kuo TT, Chu MT, Ma HI, Chiang YH, Huang EY. Postnatal systemic inflammation exacerbates impairment of hippocampal synaptic plasticity in an animal seizure model. NeuroImmunoModulation. 2013;20(4):223–32. https://doi.org/10.1159/000348440.CrossRef

40.

Kjelstrup KG, Tuvnes FA, Steffenach HA, Murison R, Moser EI, Moser MB. Reduced fear expression after lesions of the ventral hippocampus. Proc Natl Acad Sci USA. 2002;99(16):10825–30. https://doi.org/10.1073/pnas.152112399.CrossRef

41.

Fanselow MS, Dong HW. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron. 2010;65(1):7–19. https://doi.org/10.1016/j.neuron.2009.11.031.CrossRef

42.

Chockanathan U, Padmanabhan K. Divergence in population coding for space between dorsal and ventral CA1. eNeuro. 2021;8(5):ENEURO.0211-21.2021. https://doi.org/10.1523/ENEURO.0211-21.2021.CrossRef

43.

Doosti MH, Bakhtiari A, Zare P, Amani M, Majidi-Zolbanin N, Babri S, Salari AA. Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2013;43:55–65. https://doi.org/10.1016/j.pnpbp.2012.12.003.CrossRef

44.

Majidi J, Kosari-Nasab M, Salari AA. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice. Brain Res Bull. 2016;120:1–13. https://doi.org/10.1016/j.brainresbull.2015.10.009.CrossRef

45.

Zhou R, Bai Y, Yang R, Zhu Y, Chi X, Li L, Chen L, Sokabe M. Abnormal synaptic plasticity in basolateral amygdala may account for hyperactivity and attention-deficit in male rat exposed perinatally to low-dose bisphenol-A. Neuropharmacology. 2011;60(5):789–98. https://doi.org/10.1016/j.neuropharm.2011.01.031.CrossRef

46.

Fanselow MS, Poulos AM. The neuroscience of mammalian associative learning. Annu Rev Psychol. 2005;56:207–34. https://doi.org/10.1146/annurev.psych.56.091103.070213.CrossRef

47.

Lynch MA. Long-term potentiation and memory. Physiol Rev. 2004;84(1):87–136. https://doi.org/10.1152/physrev.00014.2003.CrossRef

48.

Tang X, Kim J, Zhou L, Wengert E, Zhang L, Wu Z, Carromeu C, Muotri AR, Marchetto MC, Gage FH, Chen G. KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome. Proc Natl Acad Sci USA. 2016;113(3):751–6. https://doi.org/10.1073/pnas.1524013113.CrossRef

49.

Blaesse P, Airaksinen MS, Rivera C, Kaila K. Cation-chloride cotransporters and neuronal function. Neuron. 2009;61(6):820–38. https://doi.org/10.1016/j.neuron.2009.03.003.CrossRef

50.

Pierre WC, Legault LM, Londono I, McGraw S, Lodygensky GA. Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups. Faseb j. 2020;34(1):432–45. https://doi.org/10.1096/fj.201901461R.CrossRef

51.

Maccari S, Polese D, Reynaert ML, Amici T, Morley-Fletcher S, Fagioli F. Early-life experiences and the development of adult diseases with a focus on mental illness: the human birth theory. Neuroscience. 2017;342:232–51. https://doi.org/10.1016/j.neuroscience.2016.05.042.CrossRef

52.

Simanek AM, Meier HC. Association between prenatal exposure to maternal infection and offspring mood disorders: a review of the literature. Curr Probl Pediatr Adolesc Health Care. 2015;45(11):325–64. https://doi.org/10.1016/j.cppeds.2015.06.008.CrossRef

53.

Zheng ZH, Tu JL, Li XH, Hua Q, Liu WZ, Liu Y, Pan BX, Hu P, Zhang WH. Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala. Brain Behav Immun. 2021;91:505–18. https://doi.org/10.1016/j.bbi.2020.11.007.CrossRef

54.

Chamera K, Kotarska K, Szuster-Głuszczak M, Trojan E, Skórkowska A, Pomierny B, Krzyżanowska W, Bryniarska N, Basta-Kaim A. The prenatal challenge with lipopolysaccharide and polyinosinic:polycytidylic acid disrupts CX3CL1-CX3CR1 and CD200-CD200R signalling in the brains of male rat offspring: a link to schizophrenia-like behaviours. J Neuroinflammation. 2020;17(1):247. https://doi.org/10.1186/s12974-020-01923-0.CrossRef

55.

Claypoole LD, Zimmerberg B, Williamson LL. Neonatal lipopolysaccharide treatment alters hippocampal neuroinflammation, microglia morphology and anxiety-like behavior in rats selectively bred for an infantile trait. Brain Behav Immun. 2017;59:135–46. https://doi.org/10.1016/j.bbi.2016.08.017.CrossRef

56.

Rogers JT, Morganti JM, Bachstetter AD, Hudson CE, Peters MM, Grimmig BA, Weeber EJ, Bickford PC, Gemma C. CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. J Neurosci. 2011;31(45):16241–50. https://doi.org/10.1523/jneurosci.3667-11.2011.CrossRef

57.

Daumas S, Halley H, Francés B, Lassalle JM. Encoding, consolidation, and retrieval of contextual memory: differential involvement of dorsal CA3 and CA1 hippocampal subregions. Learn Mem. 2005;12(4):375–82. https://doi.org/10.1101/lm.81905.CrossRef

58.

Akbari E, Naghdi N, Motamedi F. The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze. Peptides. 2007;28(3):650–6. https://doi.org/10.1016/j.peptides.2006.11.002.CrossRef

59.

Banks MI, Hardie JB, Pearce RA. Development of GABA(A) receptor-mediated inhibitory postsynaptic currents in hippocampus. J Neurophysiol. 2002;88(6):3097–107. https://doi.org/10.1152/jn.00026.2002.CrossRef

60.

Wu X, Huang L, Wu Z, Zhang C, Jiang D, Bai Y, Wang Y, Chen G. Homeostatic competition between phasic and tonic inhibition. J Biol Chem. 2013;288(35):25053–65. https://doi.org/10.1074/jbc.M113.491464.CrossRef

61.

Caraiscos VB, Elliott EM, You-Ten KE, Cheng VY, Belelli D, Newell JG, Jackson MF, Lambert JJ, Rosahl TW, Wafford KA, MacDonald JF, Orser BA. Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors. Proc Natl Acad Sci USA. 2004;101(10):3662–7. https://doi.org/10.1073/pnas.0307231101.CrossRef

62.

Cheng VY, Martin LJ, Elliott EM, Kim JH, Mount HT, Taverna FA, Roder JC, Macdonald JF, Bhambri A, Collinson N, Wafford KA, Orser BA. Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J Neurosci. 2006;26(14):3713–20. https://doi.org/10.1523/jneurosci.5024-05.2006.CrossRef

63.

Martin LJ, Oh GH, Orser BA. Etomidate targets alpha5 gamma-aminobutyric acid subtype A receptors to regulate synaptic plasticity and memory blockade. Anesthesiology. 2009;111(5):1025–35. https://doi.org/10.1097/ALN.0b013e3181bbc961.CrossRef

64.

Kaila K, Price TJ, Payne JA, Puskarjov M, Voipio J. Cation-chloride cotransporters in neuronal development, plasticity and disease. Nat Rev Neurosci. 2014;15(10):637–54. https://doi.org/10.1038/nrn3819.CrossRef

65.

Blaesse P, Schmidt T. K-Cl cotransporter KCC2–a moonlighting protein in excitatory and inhibitory synapse development and function. Pflugers Arch. 2015;467(4):615–24. https://doi.org/10.1007/s00424-014-1547-6.CrossRef

66.

Dargaei Z, Bang JY, Mahadevan V, Khademullah CS, Bedard S, Parfitt GM, Kim JC, Woodin MA. Restoring GABAergic inhibition rescues memory deficits in a Huntington’s disease mouse model. Proc Natl Acad Sci USA. 2018;115(7):E1618–26. https://doi.org/10.1073/pnas.1716871115.CrossRef

67.

Liu R, Wang J, Liang S, Zhang G, Yang X. Role of NKCC1 and KCC2 in epilepsy: from expression to function. Front Neurol. 2019;10:1407. https://doi.org/10.3389/fneur.2019.01407.CrossRef

68.

Kahle KT, Khanna AR, Duan J, Staley KJ, Delpire E, Poduri A. The KCC2 cotransporter and human epilepsy: getting excited about inhibition. Neuroscientist. 2016;22(6):555–62. https://doi.org/10.1177/1073858416645087.CrossRef

69.

Kitayama T. The role of K(+)-Cl(-)-cotransporter-2 in neuropathic pain. Neurochem Res. 2018;43(1):110–5. https://doi.org/10.1007/s11064-017-2344-3.CrossRef

70.

Boulenguez P, Liabeuf S, Bos R, Bras H, Jean-Xavier C, Brocard C, Stil A, Darbon P, Cattaert D, Delpire E, Marsala M, Vinay L. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med. 2010;16(3):302–7. https://doi.org/10.1038/nm.2107.CrossRef

71.

de Ferron BS, Vilpoux C, Kervern M, Robert A, Antol J, Naassila M, Pierrefiche O. Increase of KCC2 in hippocampal synaptic plasticity disturbances after perinatal ethanol exposure. Addict Biol. 2017;22(6):1870–82. https://doi.org/10.1111/adb.12465.CrossRef

72.

Jiang J, Tang B, Wang L, Huo Q, Tan S, Misrani A, Han Y, Li H, Hu H, Wang J, Cheng T, Tabassum S, Chen M, Xie W, Long C, Yang L. Systemic LPS-induced microglial activation results in increased GABAergic tone: a mechanism of protection against neuroinflammation in the medial prefrontal cortex in mice. Brain Behav Immun. 2022;99:53–69. https://doi.org/10.1016/j.bbi.2021.09.017.CrossRef

73.

Järlestedt K, Naylor AS, Dean J, Hagberg H, Mallard C. Decreased survival of newborn neurons in the dorsal hippocampus after neonatal LPS exposure in mice. Neuroscience. 2013;253:21–8. https://doi.org/10.1016/j.neuroscience.2013.08.040.CrossRef

74.

Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447(7143):425–32. https://doi.org/10.1038/nature05918.CrossRef

75.

Kundakovic M, Jaric I. The epigenetic link between prenatal adverse environments and neurodevelopmental disorders. Genes. 2017;8(3):104. https://doi.org/10.3390/genes8030104.CrossRef

76.

Grayson DR, Guidotti A. The dynamics of DNA methylation in schizophrenia and related psychiatric disorders. Neuropsychopharmacology. 2013;38(1):138–66. https://doi.org/10.1038/npp.2012.125.CrossRef

77.

Rivera C, Voipio J, Thomas-Crusells J, Li H, Emri Z, Sipilä S, Payne JA, Minichiello L, Saarma M, Kaila K. Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. J Neurosci. 2004;24(19):4683–91. https://doi.org/10.1523/jneurosci.5265-03.2004.CrossRef

78.

Zhang Z, Wang X, Wang W, Lu YG, Pan ZZ. Brain-derived neurotrophic factor-mediated downregulation of brainstem K+-Cl- cotransporter and cell-type-specific GABA impairment for activation of descending pain facilitation. Mol Pharmacol. 2013;84(4):511–20. https://doi.org/10.1124/mol.113.086496.CrossRef

79.

Shulga A, Thomas-Crusells J, Sigl T, Blaesse A, Mestres P, Meyer M, Yan Q, Kaila K, Saarma M, Rivera C, Giehl KM. Posttraumatic GABA(A)-mediated [Ca2+]i increase is essential for the induction of brain-derived neurotrophic factor-dependent survival of mature central neurons. J Neurosci. 2008;28(27):6996–7005. https://doi.org/10.1523/jneurosci.5268-07.2008.CrossRef

80.

Taylor RA, Ai Y, Sansing LH. Abstract TMP55 TGF-β1 induces microglial BDNF production and improves functional outcome after intracerebral hemorrhage. Stroke. 2016;47(suppl_1):ATMP55. https://doi.org/10.1161/str.47.suppl_1.tmp55.CrossRef

81.

Hu Y, Chen W, Wu L, Jiang L, Liang N, Tan L, Liang M, Tang N. TGF-β1 restores hippocampal synaptic plasticity and memory in Alzheimer model via the PI3K/Akt/Wnt/β-Catenin signaling pathway. J Mol Neurosci. 2019;67(1):142–9. https://doi.org/10.1007/s12031-018-1219-7.CrossRef

82.

Chin J, Liu RY, Cleary LJ, Eskin A, Byrne JH. TGF-beta1-induced long-term changes in neuronal excitability in aplysia sensory neurons depend on MAPK. J Neurophysiol. 2006;95(5):3286–90. https://doi.org/10.1152/jn.00770.2005.CrossRef

83.

Caraci F, Gulisano W, Guida CA, Impellizzeri AA, Drago F, Puzzo D, Palmeri A. A key role for TGF-β1 in hippocampal synaptic plasticity and memory. Sci Rep. 2015;5:11252. https://doi.org/10.1038/srep11252.CrossRef

Title: Neonatal inflammation increases hippocampal KCC2 expression through methylation-mediated TGF-β1 downregulation leading to impaired hippocampal cognitive function and synaptic plasticity in adult mice
Authors: Jing Rong
Yang Yang
Min Liang
Haiquan Zhong
Yingchun Li
Yichao Zhu
Sha Sha
Lei Chen
Rong Zhou
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Cytokines
Published in: Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-023-02697-x

2024 ASCO Annual Meeting

Springer Medicine

Neonatal inflammation increases hippocampal KCC2 expression through methylation-mediated TGF-β1 downregulation leading to impaired hippocampal cognitive function and synaptic plasticity in adult mice

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2023

A short peptide exerts neuroprotective effects on cerebral ischemia–reperfusion injury by reducing inflammation via the miR-6328/IKKβ/NF-κB axis

Supporting the differential diagnosis of connective tissue diseases with neurological involvement by blood and cerebrospinal fluid flow cytometry

The short isoform of MS4A7 is a novel player in glioblastoma microenvironment, M2 macrophage polarization, and tumor progression

Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis

Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis

Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury