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Open Access 01-07-2020 | Schizophrenia | Original Article

Glutamic acid decarboxylase 67 haplodeficiency in mice: consequences of postweaning social isolation on behavior and changes in brain neurochemical systems

Authors: Sven Nullmeier, Christoph Elmers, Wolfgang D’Hanis, Kiran Veer Kaur Sandhu, Oliver Stork, Yuchio Yanagawa, Patricia Panther, Herbert Schwegler

Published in: Brain Structure and Function | Issue 6/2020

Abstract

Reductions of glutamate acid decarboxylase (GAD67) and subsequent GABA levels have been consistently observed in neuropsychiatric disorders like schizophrenia and depression, but it has remained unclear how GABAergic dysfunction contributes to different symptoms of the diseases. To address this issue, we investigated male mice haplodeficient for GAD67 (GAD67^+/GFP mice), which showed a reduced social interaction, social dominance and increased immobility in the forced swim test. No differences were found in rotarod performance and sensorimotor gating. We also addressed potential effects of social deprivation, which is known, during early life, to affect GABAergic function and induces behavioral abnormalities similar to the symptoms found in psychiatric disorders. Indeed, social isolation of GAD67^+/GFP mice provoked increased rearing activity in the social interaction test and hyperlocomotion on elevated plus maze. Since GABA closely interacts with the dopaminergic, serotonergic and cholinergic neurotransmitter systems, we investigated GAD67^+/GFP and GAD67^+/+ mice for morphological markers of the latter systems and found increased tyrosine hydroxylase (TH)-IR fiber densities in CA1 of dorsal hippocampus. By contrast, no differences in numbers and densities of TH-positive neurons of the midbrain dopamine regions, serotonin (5-HT) neurons of the raphe nuclei, or choline acetyltransferase (ChAT)-expressing neurons of basal forebrain and their respective terminal fields were observed. Our results indicate that GAD67 haplodeficiency impairs sociability and increases vulnerability to social stress, provokes depressive-like behavior and alters the catecholaminergic innervation in brain areas associated with schizophrenia. GAD67^+/GFP mice may provide a useful model for studying the impact of GABAergic dysfunction as related to neuropsychiatric disorders.

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Abdallah CG, Jackowski A, Sato JR, Mao X, Kang G, Cheema R, Coplan JD, Mathew SJ, Shungu DC (2015) Prefrontal cortical GABA abnormalities are associated with reduced hippocampal volume in major depressive disorder. Eur Neuropsychopharmacol 25(8):1082–1090. https://doi.org/10.1016/j.euroneuro.2015.04.025 CrossRefPubMedPubMedCentral

Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94:239–247. https://doi.org/10.1002/ar.1090940210 CrossRefPubMed

Abramov U, Raud S, Kõks S, Innos J, Kurrikoff K, Matsui T, Vasar E (2004) Targeted mutation of CCK2 receptor gene antagonises behavioural changes induced by social isolation in female, but not in male mice. Behav Brain Res 155(1):1–11. https://doi.org/10.1016/j.bbr.2004.03.027 CrossRefPubMed

Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE Jr, Jones EG (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 52(4):258–266. https://doi.org/10.1001/archpsyc.1995.03950160008002 CrossRefPubMed

Aley KO, Kulkarni SK (1989) GABA-mediated modification of despair behavior in mice. Naunyn Schmiedebergs Arch Pharmacol 339(3):306–311. https://doi.org/10.1007/bf00173583 CrossRefPubMed

Andreasen NC, Flaum M, Swayze VW, Tyrrell G, Arndt S (1990) Positive and negative symptoms in schizophrenia A critical reappraisal. Arch Gen Psychiatry 47(7):615–621. https://doi.org/10.1001/archpsyc.1990.01810190015002 CrossRefPubMed

Asada H, Kawamura Y, Maruyama K, Kume H, Ding RG, Kanbara N, Kuzume H, Sanbo M, Yagi T, Obata K (1997) Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci USA 94(12):6496–6499. https://doi.org/10.1073/pnas.94.12.6496 CrossRefPubMedPubMedCentral

Asan E (1993) Comparative single and double immunolabelling with antisera against catecholamine biosynthetic enzymes: criteria for the identification of dopaminergic, noradrenergic and adrenergic structures in selected rat brain areas. Histochemistry 99(6):427–442. https://doi.org/10.1007/BF00274095 CrossRefPubMed

Asan E (1997) Ultrastructural features of tyrosine-hydroxylase-immunoreactive afferents and their targets in the rat amygdala. Cell Tissue Res 288(3):449–469. https://doi.org/10.1007/s004410050832 CrossRefPubMed

Bayer TA, Falkai P, Maier W (1999) Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the "two hit hypothesis". JPsychiatrRes 33(6):543–548. https://doi.org/10.1016/S0022-3956(99)00039-4 CrossRef

Belforte JE, Zsiros V, Sklar ER, Jiang Z, Yu G, Li Y, Quinlan EM, Nakazawa K (2010) Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci 13(1):76–83. https://doi.org/10.1038/nn.2447 CrossRefPubMed

Benes FM, Berretta S (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25(1):1–27. https://doi.org/10.1016/S0893-133X(01)00225-1 CrossRefPubMed

Bicks LK, Koike H, Akbarian S, Morishita H (2015) Prefrontal cortex and social cognition in mouse and man. Front Psychol 6:1805. https://doi.org/10.3389/fpsyg.2015.01805 CrossRefPubMedPubMedCentral

Borsini F, Mancinelli A, D'Aranno V, Evangelista S, Meli A (1988) On the role of endogenous GABA in the forced swimming test in rats. Pharmacol Biochem Behav 29(2):275–279. https://doi.org/10.1016/0091-3057(88)90156-6 CrossRefPubMed

Borsini F, Meli A (1988) Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 94(2):147–160. https://doi.org/10.1007/BF00176837 CrossRefPubMed

Bothe GW, Bolivar VJ, Vedder MJ, Geistfeld JG (2005) Behavioral differences among fourteen inbred mouse strains commonly used as disease models. Comp Med 55(4):326–334. https://www.ncbi.nlm.nih.gov/pubmed/16158908

Braff DL, Geyer MA, Swerdlow NR (2001) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156(2–3):234–258. https://doi.org/10.1007/s002130100810 CrossRefPubMed

Brisch R, Saniotis A, Wolf R, Bielau H, Bernstein HG, Steiner J, Bogerts B, Braun K, Jankowski Z, Kumaratilake J, Henneberg M, Gos T (2014) The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front Psychiatry 5:47. https://doi.org/10.3389/fpsyt.2014.00047 CrossRefPubMedPubMedCentral

Brown RE, McKenna JT, Winston S, Basheer R, Yanagawa Y, Thakkar MM, McCarley RW (2008) Characterization of GABAergic neurons in rapid-eye-movement sleep controlling regions of the brainstem reticular formation in GAD67-green fluorescent protein knock-in mice. Eur J Neurosci 27(2):352–363. https://doi.org/10.1111/j.1460-9568.2008.06024.x CrossRefPubMedPubMedCentral

Czeh B, Vardya I, Varga Z, Febbraro F, Csabai D, Martis LS, Hojgaard K, Henningsen K, Bouzinova EV, Miseta A, Jensen K, Wiborg O (2018) Long-term stress disrupts the structural and functional integrity of GABAergic neuronal networks in the medial prefrontal cortex of rats. Front Cell Neurosci 12:148. https://doi.org/10.3389/fncel.2018.00148 CrossRefPubMedPubMedCentral

Czeh B, Varga ZK, Henningsen K, Kovacs GL, Miseta A, Wiborg O (2015) Chronic stress reduces the number of GABAergic interneurons in the adult rat hippocampus, dorsal-ventral and region-specific differences. Hippocampus 25(3):393–405. https://doi.org/10.1002/hipo.22382 CrossRefPubMed

de Jonge JC, Vinkers CH, Hulshoff Pol HE, Marsman A (2017) GABAergic mechanisms in schizophrenia: linking postmortem and in vivo studies. Front Psychiatry 8:118–118. https://doi.org/10.3389/fpsyt.2017.00118 CrossRefPubMedPubMedCentral

Ellenbroek BA, Cools AR (2000) Animal models for the negative symptoms of schizophrenia. Behav Pharmacol 11(3–4):223–233CrossRefPubMed

Fatemi SH, Stary JM, Earle JA, Araghi-Niknam M, Eagan E (2005) GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum. SchizophrRes 72(2–3):109–122. http://www.ncbi.nlm.nih.gov/pubmed/15560956

Ferguson BR, Gao W-J (2018) PV interneurons: critical regulators of E/I balance for prefrontal cortex-dependent behavior and psychiatric disorders. Front Neural Circuits 12:37–37. https://doi.org/10.3389/fncir.2018.00037 CrossRefPubMedPubMedCentral

File SE, Kenny PJ, Ouagazzal AM (1998) Bimodal modulation by nicotine of anxiety in the social interaction test: role of the dorsal hippocampus. Behav Neurosci 112(6):1423–1429. https://doi.org/10.1037/0735-7044.112.6.1423 CrossRefPubMed

File SE, Seth P (2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463(1–3):35–53. https://doi.org/10.1016/S0014-2999(03)01273-1 CrossRefPubMed

Fogaca MV, Duman RS (2019) Cortical GABAergic dysfunction in stress and depression: new insights for therapeutic interventions. Front Cell Neurosci 13:87. https://doi.org/10.3389/fncel.2019.00087 CrossRefPubMedPubMedCentral

Fone KC, Porkess MV (2008) Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev 32(6):1087–1102. https://doi.org/10.1016/j.neubiorev.2008.03.003 CrossRefPubMed

Fujihara K, Miwa H, Kakizaki T, Kaneko R, Mikuni M, Tanahira C, Tamamaki N, Yanagawa Y (2015) Glutamate decarboxylase 67 deficiency in a subset of GABAergic neurons induces schizophrenia-related phenotypes. Neuropsychopharmacology 40(10):2475–2486. https://doi.org/10.1038/npp.2015.117 CrossRefPubMedPubMedCentral

Gaskin PL, Toledo-Rodriguez M, Alexander SP, Fone KC (2016) Down-regulation of hippocampal genes regulating dopaminergic, GABAergic, and glutamatergic function following combined neonatal phencyclidine and post-weaning social isolation of rats as a neurodevelopmental model for schizophrenia. Int J Neuropsychopharmacol 19(11):62. https://doi.org/10.1093/ijnp/pyw062 CrossRef

Geyer MA, Vollenweider FX (2008) Serotonin research: contributions to understanding psychoses. Trends Pharmacol Sci 29(9):445–453. https://doi.org/10.1016/j.tips.2008.06.006 CrossRefPubMed

Glausier JR, Kimoto S, Fish KN, Lewis DA (2015) Lower glutamic acid decarboxylase 65-kDa isoform messenger RNA and protein levels in the prefrontal cortex in schizoaffective disorder but not schizophrenia. Biol Psychiatry 77(2):167–176. https://doi.org/10.1016/j.biopsych.2014.05.010 CrossRefPubMed

Grace AA (2012) Dopamine system dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. Neuropharmacology 62(3):1342–1348. https://doi.org/10.1016/j.neuropharm.2011.05.011 CrossRefPubMed

Guidotti A, Auta J, Davis JM, Di-Giorgi-Gerevini V, Dwivedi Y, Grayson DR, Impagnatiello F, Pandey G, Pesold C, Sharma R, Uzunov D, Costa E (2000) Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 57(11):1061–1069. https://doi.org/10.1001/archpsyc.57.11.1061 CrossRefPubMed

Guillin O, Abi-Dargham A, Laruelle M (2007) Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol 78:1–39. https://doi.org/10.1016/S0074-7742(06)78001-1 CrossRefPubMed

Haber SN (2003) The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 26(4):317–330. https://doi.org/10.1016/j.jchemneu.2003.10.003 CrossRefPubMed

Häfner H, Löffler W, Maurer K, Hambrecht M, Wad H (1999) Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia. Acta Psychiatr Scand 100(2):105–118. https://doi.org/10.1111/j.1600-0447.1999.tb10831.x CrossRefPubMed

Hall FS, Huang S, Fong GF, Pert A (1998) The effects of social isolation on the forced swim test in Fawn hooded and Wistar rats. J Neurosci Methods 79(1):47–51. https://doi.org/10.1016/S0165-0270(97)00155-6 CrossRefPubMed

Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z, Sampson AR, Lewis DA (2003) Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 23(15):6315–6326. https://doi.org/10.1523/JNEUROSCI.23-15-06315.2003 CrossRefPubMedPubMedCentral

Hickey AJ, Reynolds JN, Beninger RJ (2012) Post-weaning social isolation and subchronic NMDA glutamate receptor blockade: effects on locomotor activity and GABA signaling in the rat suggest independent mechanisms. Pharmacol Biochem Behav 101(2):231–238. https://doi.org/10.1016/j.pbb.2012.01.015 CrossRefPubMed

Howes OD, Kapur S (2009) The dopamine hypothesis of schizophrenia: version III–the final common pathway. Schizophr Bull 35(3):549–562. https://doi.org/10.1093/schbul/sbp006 CrossRefPubMedPubMedCentral

Janitzky K, Schwegler H, Krober A, Roskoden T, Yanagawa Y, Linke R (2011) Species-relevant inescapable stress differently influences memory consolidation and retrieval of mice in a spatial radial arm maze. Behav Brain Res 219(1):142–148. https://doi.org/10.1016/j.bbr.2010.12.032 CrossRefPubMed

Jones CA, Watson DJ, Fone KC (2011) Animal models of schizophrenia. Br J Pharmacol 164(4):1162–1194. https://doi.org/10.1111/j.1476-5381.2011.01386.x CrossRefPubMedPubMedCentral

Kalkman HO, Loetscher E (2003) GAD(67): the link between the GABA-deficit hypothesis and the dopaminergic- and glutamatergic theories of psychosis. J Neural Transm (Vienna) 110(7):803–812. https://doi.org/10.1007/s00702-003-0826-8 CrossRef

Kapur S, Remington G (1996) Serotonin-dopamine interaction and its relevance to schizophrenia. Am J Psychiatry 153(4):466–476. https://doi.org/10.1176/ajp.153.4.466 CrossRefPubMed

Kolata SM, Nakao K, Jeevakumar V, Farmer-Alroth EL, Fujita Y, Bartley AF, Jiang SZ, Rompala GR, Sorge RE, Jimenez DV, Martinowich K, Mateo Y, Hashimoto K, Dobrunz LE, Nakazawa K (2018) Neuropsychiatric phenotypes produced by GABA reduction in mouse cortex and hippocampus. Neuropsychopharmacology 43(6):1445–1456. https://doi.org/10.1038/npp.2017.296 CrossRefPubMedPubMedCentral

Kulesskaya N, Rauvala H, Voikar V (2011) Evaluation of social and physical enrichment in modulation of behavioural phenotype in C57BL/6J female mice. PLoS ONE 6(9):e24755. https://doi.org/10.1371/journal.pone.0024755 CrossRefPubMedPubMedCentral

Laviola G, Adriani W, Gaudino C, Marino R, Keller F (2006) Paradoxical effects of prenatal acetylcholinesterase blockade on neuro-behavioral development and drug-induced stereotypies in reeler mutant mice. Psychopharmacology 187(3):331–344. https://doi.org/10.1007/s00213-006-0426-z CrossRefPubMed

Laviolette SR (2007) Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia? Schizophr Bull 33(4):971–981. https://doi.org/10.1093/schbul/sbm048 CrossRefPubMedPubMedCentral

Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6(4):312–324. https://doi.org/10.1038/nrn1648 CrossRefPubMed

Lewis DA, Levitt P (2002) Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25:409–432. https://doi.org/10.1146/annurev.neuro.25.112701.142754 CrossRefPubMed

Lim AL, Taylor DA, Malone DT (2012) A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat. J Psychopharmacol 26(9):1252–1264. https://doi.org/10.1177/0269881111430751 CrossRefPubMed

Lindzey G, Winston H, Manosevitz M (1961) Social dominance in inbred mouse strains. Nature 191(4787):474–476. https://doi.org/10.1038/191474a0 CrossRefPubMed

Lino-de-Oliveira C, Lima TCMD, Carobrez AdP (2005) Structure of the rat behaviour in the forced swimming test. Behav Brain Res 158(2):243–250. https://doi.org/10.1016/j.bbr.2004.09.004 CrossRefPubMed

Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31(5):234–242. https://doi.org/10.1016/j.tins.2008.02.005 CrossRefPubMedPubMedCentral

Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92(2):180–185. https://doi.org/10.1007/BF00177912 CrossRefPubMed

Lodge DJ, Grace AA (2011a) Developmental pathology, dopamine, stress and schizophrenia. Int J Dev Neurosci 29(3):207–213. https://doi.org/10.1016/j.ijdevneu.2010.08.002 CrossRefPubMed

Lodge DJ, Grace AA (2011b) Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends Pharmacol Sci 32(9):507–513. https://doi.org/10.1016/j.tips.2011.05.001 CrossRefPubMedPubMedCentral

Luscher B, Fuchs T (2015) GABAergic control of depression-related brain states. Adv Pharmacol 73:97–144. https://doi.org/10.1016/bs.apha.2014.11.003 CrossRefPubMedPubMedCentral

MacQueen GM, Yucel K, Taylor VH, Macdonald K, Joffe R (2008) Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biol Psychiatry 64(10):880–883. https://doi.org/10.1016/j.biopsych.2008.06.027 CrossRefPubMed

Marowsky A, Yanagawa Y, Obata K, Vogt KE (2005) A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron 48(6):1025–1037. https://doi.org/10.1016/j.neuron.2005.10.029 CrossRefPubMed

Matrisciano F, Tueting P, Dalal I, Kadriu B, Grayson DR, Davis JM, Nicoletti F, Guidotti A (2013) Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology 68:184–194. https://doi.org/10.1016/j.neuropharm.2012.04.013 CrossRefPubMed

Matta R, Tiessen AN, Choleris E (2017) The role of dorsal hippocampal dopamine D1-type receptors in social learning, social interactions, and food intake in male and female mice. Neuropsychopharmacology 42(12):2344–2353. https://doi.org/10.1038/npp.2017.43 CrossRefPubMedPubMedCentral

Meltzer HY, Stahl SM (1976) The dopamine hypothesis of schizophrenia: a review. Schizophr Bull 2(1):19–76. https://doi.org/10.1093/schbul/2.1.19 CrossRefPubMed

Miczek KA, Weerts E, Haney M, Tidey J (1994) Neurobiological mechanisms controlling aggression: preclinical developments for pharmacotherapeutic interventions. Neurosci Biobehav Rev 18(1):97–110. https://doi.org/10.1016/0149-7634(94)90040-X CrossRefPubMed

Miczek KA, Fish EW, De Bold JF (2003) Neurosteroids, GABAA receptors, and escalated aggressive behavior. Horm Behav 44(3):242–257. https://www.ncbi.nlm.nih.gov/pubmed/14609546

Müller I, Caliskan G, Stork O (2015) The GAD65 knock out mouse - a model for GABAergic processes in fear- and stress-induced psychopathology. Genes Brain Behav 14(1):37–45. https://doi.org/10.1111/gbb.12188 CrossRefPubMed

Narvaes R, Martins de Almeida RM (2014) Aggressive behavior and three neurotransmitters: dopamine, GABA, and serotonin—a review of the last 10 years. Psychol Neurosci 7(4):601–607. https://doi.org/10.3922/j.psns.2014.4.20 CrossRef

Nelson RJ, Chiavegatto S (2000) Aggression in knockout mice. ILAR J 41(3):153–162. https://doi.org/10.1093/ilar.41.3.153 CrossRefPubMed

Nullmeier S, Panther P, Frotscher M, Zhao S, Schwegler H (2014) Alterations in the hippocampal and striatal catecholaminergic fiber densities of heterozygous reeler mice. Neuroscience 275:404–419. https://doi.org/10.1016/j.neuroscience.2014.06.027 CrossRefPubMed

Panther P, Nullmeier S, Dobrowolny H, Schwegler H, Wolf R (2012) CPB-K mice a mouse model of schizophrenia? Differences in dopaminergic, serotonergic and behavioral markers compared to BALB/cJ mice. Behav Brain Res 230(1):215–228. https://doi.org/10.1016/j.bbr.2012.02.018 CrossRefPubMed

Paxinos G, Franklin KBJ (2004) The mouse brain in stereotaxic coordinates: compact, 2nd edn. Elsevier Academic Press, San Diego

Pietropaolo S, Singer P, Feldon J, Yee BK (2008) The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex. Psychopharmacology 197(4):613–628. https://doi.org/10.1007/s00213-008-1081-3 CrossRefPubMed

Pokos V, Castle D (2006) Prevalence of comorbid anxiety disorders in schizophrenia spectrum disorders: a literature review. Curr Psychiatry Rev 2(3):285–307. https://doi.org/10.2174/157340006778018193 CrossRef

Poncelet M, Martin P, Danti S, Simon P, Soubrie P (1987) Noradrenergic rather than GABAergic processes as the common mediation of the antidepressant profile of GABA agonists and imipramine-like drugs in animals. Pharmacol Biochem Behav 28(3):321–326. https://doi.org/10.1016/0091-3057(87)90447-3 CrossRefPubMed

Raedler TJ, Bymaster FP, Tandon R, Copolov D, Dean B (2007) Towards a muscarinic hypothesis of schizophrenia. Mol Psychiatry 12(3):232–246. https://doi.org/10.1038/sj.mp.4001924 CrossRefPubMed

Ragland JD, Layher E, Hannula DE, Niendam TA, Lesh TA, Solomon M, Carter CS, Ranganath C (2017) Impact of schizophrenia on anterior and posterior hippocampus during memory for complex scenes. Neuroimage Clin 13:82–88. https://doi.org/10.1016/j.nicl.2016.11.017 CrossRefPubMed

Rajkowska G, O'Dwyer G, Teleki Z, Stockmeier CA, Miguel-Hidalgo JJ (2007) GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression. Neuropsychopharmacology 32(2):471–482. https://doi.org/10.1038/sj.npp.1301234 CrossRefPubMed

Rodgers RJ, Lee C, Shepherd JK (1992) Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend upon treatment regimen and prior maze experience. Psychopharmacology 106(1):102–110. https://doi.org/10.1007/BF02253596 CrossRefPubMed

Sams-Dodd F (1995) Automation of the social interaction test by a video-tracking system: behavioural effects of repeated phencyclidine treatment. J Neurosci Methods 59(2):157–167. https://doi.org/10.1016/0165-0270(94)00173-E CrossRefPubMed

Samsom JN, Wong AH (2015) Schizophrenia and depression co-morbidity: what we have learned from animal models. Front Psychiatry 6:13. https://doi.org/10.3389/fpsyt.2015.00013 CrossRefPubMedPubMedCentral

Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH (1999) Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 56(11):1043–1047. https://doi.org/10.1001/archpsyc.56.11.1043 CrossRefPubMed

Sandhu KV, Lang D, Muller B, Nullmeier S, Yanagawa Y, Schwegler H, Stork O (2014) Glutamic acid decarboxylase 67 haplodeficiency impairs social behavior in mice. Genes Brain Behav 13(4):439–450. https://doi.org/10.1111/gbb.12131 CrossRefPubMed

Savitz J, Drevets WC (2009) Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 33(5):699–771. https://doi.org/10.1016/j.neubiorev.2009.01.004 CrossRefPubMedPubMedCentral

Scarr E, Gibbons AS, Neo J, Udawela M, Dean B (2013) Cholinergic connectivity: it's implications for psychiatric disorders. Front Cell Neurosci 7:55. https://doi.org/10.3389/fncel.2013.00055 CrossRefPubMedPubMedCentral

Schultz EF, Tapp JT (1973) Olfactory control of behavior in rodents. Psychol Bull 79(1):21–44. https://doi.org/10.1037/h0033817 CrossRefPubMed

Shoji H, Mizoguchi K (2011) Aging-related changes in the effects of social isolation on social behavior in rats. Physiol Behav 102(1):58–62. https://doi.org/10.1016/j.physbeh.2010.10.001 CrossRefPubMed

Sibille E, Morris HM, Kota RS, Lewis DA (2011) GABA-related transcripts in the dorsolateral prefrontal cortex in mood disorders. Int J Neuropsychopharmacol 14(6):721–734. https://doi.org/10.1017/S1461145710001616 CrossRefPubMed

Simpson J, Bree D, Kelly JP (2012) Effect of early life housing manipulation on baseline and drug-induced behavioural responses on neurochemistry in the male rat. Prog Neuropsychopharmacol Biol Psychiatry 37(2):252–263. https://doi.org/10.1016/j.pnpbp.2012.02.008 CrossRefPubMed

Siris SG, Adan F, Cohen M, Mandeli J, Aronson A, Casey E (1988) Postpsychotic depression and negative symptoms: an investigation of syndromal overlap. Am J Psychiatry 145(12):1532–1537. https://doi.org/10.1176/ajp.145.12.1532 CrossRefPubMed

Smith KM (2018) Hyperactivity in mice lacking one allele of the glutamic acid decarboxylase 67 gene. Atten Defic Hyperact Disord 10(4):267–271. https://doi.org/10.1007/s12402-018-0254-0 CrossRefPubMed

Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467(1):60–79. https://doi.org/10.1002/cne.10905 CrossRefPubMed

Tayoshi S, Nakataki M, Sumitani S, Taniguchi K, Shibuya-Tayoshi S, Numata S, Iga J, Ueno S, Harada M, Ohmori T (2010) GABA concentration in schizophrenia patients and the effects of antipsychotic medication: a proton magnetic resonance spectroscopy study. Schizophr Res 117(1):83–91. https://doi.org/10.1016/j.schres.2009.11.011 CrossRefPubMed

Todorovic N, Micic B, Schwirtlich M, Stevanovic M, Filipovic D (2019) Subregion-specific protective effects of fluoxetine and clozapine on parvalbumin expression in medial prefrontal cortex of chronically isolated rats. Neuroscience 396:24–35. https://doi.org/10.1016/j.neuroscience.2018.11.008 CrossRefPubMed

Tueting P, Pinna G, Costa E (2008) Homozygous and heterozygous reeler mouse mutants. In: Fatemi SH (ed) Reelin glycoprotein. Springer, New York, pp 291–309. https://doi.org/10.1007/978-0-387-76761-1_20 CrossRef

Uchida T, Oki Y, Yanagawa Y, Fukuda A (2011) A heterozygous deletion in the glutamate decarboxylase 67 gene enhances maternal and fetal stress vulnerability. Neurosci Res 69(4):276–282. https://doi.org/10.1016/j.neures.2010.12.010 CrossRefPubMed

Uchida T, Furukawa T, Iwata S, Yanagawa Y, Fukuda A (2014) Selective loss of parvalbumin-positive GABAergic interneurons in the cerebral cortex of maternally stressed Gad1-heterozygous mouse offspring. Transl Psychiatry 4:e371. https://doi.org/10.1038/tp.2014.13 CrossRefPubMedPubMedCentral

Varty GB, Powell SB, Lehmann-Masten V, Buell MR, Geyer MA (2006) Isolation rearing of mice induces deficits in prepulse inhibition of the startle response. Behav Brain Res 169(1):162–167. https://doi.org/10.1016/j.bbr.2005.11.025 CrossRefPubMed

Vieira C, De Lima TCM, Carobrez AD, Lino-De-Oliveira C (2008) Frequency of climbing behavior as a predictor of altered motor activity in rat forced swimming test. Neurosci Lett 445(2):170–173. https://doi.org/10.1016/j.neulet.2008.09.001 CrossRefPubMed

Voikar V, Polus A, Vasar E, Rauvala H (2005) Long-term individual housing in C57BL/6J and DBA/2 mice: assessment of behavioral consequences. Genes Brain Behav 4(4):240–252. https://doi.org/10.1111/j.1601-183X.2004.00106.x CrossRefPubMed

Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2(2):322–328. https://doi.org/10.1038/nprot.2007.44 CrossRefPubMedPubMedCentral

Walling SG, Brown RA, Miyasaka N, Yoshihara Y, Harley CW (2012) Selective wheat germ agglutinin (WGA) uptake in the hippocampus from the locus coeruleus of dopamine-beta-hydroxylase-WGA transgenic mice. Front Behav Neurosci 6:23. https://doi.org/10.3389/fnbeh.2012.00023 CrossRefPubMedPubMedCentral

Walsh J, Desbonnet L, Clarke N, Waddington JL, O'Tuathaigh CM (2012) Disruption of exploratory and habituation behavior in mice with mutation of DISC1: an ethologically based analysis. J Neurosci Res 90(7):1445–1453. https://doi.org/10.1002/jnr.23024 CrossRefPubMed

Wang T, Sinha AS, Akita T, Yanagawa Y, Fukuda A (2018) Alterations of GABAergic neuron-associated extracellular matrix and synaptic responses in Gad1-heterozygous mice subjected to prenatal stress. Front Cell Neurosci 12:284. https://doi.org/10.3389/fncel.2018.00284 CrossRefPubMedPubMedCentral

Wang Y, Kakizaki T, Sakagami H, Saito K, Ebihara S, Kato M, Hirabayashi M, Saito Y, Furuya N, Yanagawa Y (2009) Fluorescent labeling of both GABAergic and glycinergic neurons in vesicular GABA transporter (VGAT)-venus transgenic mouse. Neuroscience 164(3):1031–1043. https://doi.org/10.1016/j.neuroscience.2009.09.010 CrossRefPubMed

Wolf R, Dobrowolny H, Nullmeier S, Bogerts B, Schwegler H (2018) Effects of neonatal excitotoxic lesions in ventral thalamus on social interaction in the rat. Eur Arch Psychiatry Clin Neurosci 268(5):461–470. https://doi.org/10.1007/s00406-017-0781-2 CrossRefPubMed

Yates G, Panksepp J, Ikemoto S, Nelson E, Conner R (1991) Social isolation effects on the “behavioral despair” forced swimming test: effect of age and duration of testing. Physiol Behav 49(2):347–353. https://doi.org/10.1016/0031-9384(91)90055-S CrossRefPubMed

Title: Glutamic acid decarboxylase 67 haplodeficiency in mice: consequences of postweaning social isolation on behavior and changes in brain neurochemical systems
Authors: Sven Nullmeier
Christoph Elmers
Wolfgang D’Hanis
Kiran Veer Kaur Sandhu
Oliver Stork
Yuchio Yanagawa
Patricia Panther
Herbert Schwegler
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keyword: Schizophrenia
Published in: Brain Structure and Function / Issue 6/2020
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-020-02087-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Glutamic acid decarboxylase 67 haplodeficiency in mice: consequences of postweaning social isolation on behavior and changes in brain neurochemical systems

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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