CoChat
Sign Up
Cited by 78Stress Responses and CortisolAnimal Behavior and Welfare StudiesNeuroscience and Neuropharmacology Research

Social isolation in rats: effects on animal welfare and molecular markers for neuroplasticity

Open access
Begni, Veronica, Sanson, Alice, Pfeiffer, Natascha, Brandwein, Christiane, Inta, Dragos, Talbot, Steven R., Riva, Marco Andrea, Gass, Peter +1 more·2020·PLOS ONE
DOI 10.1371/journal.pone.0240439PMC PMC7591026
Open this paper in CoChat — free accountOpen PDF

Abstract

Early life stress compromises brain development and can contribute to the development of mental illnesses. A common animal model used to study different facets of psychiatric disorders is social isolation from early life on. In rats, this isolation can induce long-lasting alterations in molecular expression and in behavior. Since social isolation models severe psychiatric symptoms, it is to be expected that it affects the overall wellbeing of the animals. As also promoted by the 3Rs principle, though, it is pivotal to decrease the burden of laboratory animals by limiting the number of subjects (reduce, replace) and by improving the animals' wellbeing (refine). The aim of this study was therefore to test possible refinement strategies such as resocialization and mere adult social isolation. We examined whether the alternatives still triggered the necessary phenotype while minimizing the stress load on the animals. Interestingly, we did not find reduced wellbeing-associated burrowing performance in isolated rats. The hyperactive phenotype seen in socially isolated animals was observed for rats undergoing the adult-only isolation, but resocializing ameliorated the locomotor abnormality. Isolation strongly affected markers of neuroplasticity in the prefrontal cortex independent of timing: mRNA levels of Arc, Bdnf and the pool of Bdnf transcripts with the 3' long UTR were reduced in all groups. Bdnf splice variant IV expression was reduced in lifelong-isolated animals. Some of these deficits normalized after resocialization; likewise, exon VI Bdnf mRNA levels were reduced only in animals persistently isolated. Conversely, social deprivation did not affect the expression of Gad67 and Pvb, two GABAergic markers, whereas changes occurred in the expression of dopamine d1 and d2 receptors. As adult isolation was sufficient to trigger the hyperactive phenotype and impaired neuroplasticity in the prefrontal cortex, it could be a candidate for a refinement strategy for certain research questions. To fully grade the severity of post-weaning social isolation and the alternatives, adult isolation and resocialization, a more profound and multimodal assessment approach is necessary.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0240439

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Isolation prevents all social interaction-both play and non-play-so it is unclear whether identified impairments are due to lack of play vs. lack of general social interaction, as well as additional stress that total isolation induces.

    “First, isolation prevents all social interaction—both play and non-play—so it is unclear in most of these studies whether and to what extent any identified impairments are due to the lack of play vs. the lack of general social interaction, as well as the additional stress that total isolation induces (Begni et al., 2020).”

    From Social play experience in juvenile rats is indispensable for appropriate socio-sexual behavior in adulthood in males but not females (2023) · cites this paper as Begni et al., 2020

    The Discussion reports that deprivation of social contacts impairs neuroplasticity in rats, supporting the claim that isolation removes social contact and can produce impairments. The paper does not distinguish lack of play from lack of other social interaction as causes of those impairments. It also does not establish that total isolation adds stress in these animals; the Discussion reports no altered wellbeing from isolation housing itself and describes resocialization as a temporary stressor. The indexed passages have section labels but no page numbers. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 81

  1. [1]Fone KC, Porkess MV. Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev. 2008; 32(6): 1087– 102. 10.1016/j.neubiorev.2008.03.003 18423591 · DOI · Paper page
  2. [3]Meyer-Lindenberg A, Tost H. Neural mechanisms of social risk for psychiatric disorders. Nat Neurosci. 2012; 15(5): 663– 8. 10.1038/nn.3083 22504349 · DOI
  3. [4]Meyer-Lindenberg A. Social neuroscience and mechanisms of risk for mental disorders. World Psychiatry. 2014; 13(2): 143– 4. 10.1002/wps.20121 24890061 PMC4102281 · DOI
  4. [5]Selten JP, Booij J, Buwalda B, Meyer-Lindenberg A. Biological Mechanisms Whereby Social Exclusion May Contribute to the Etiology of Psychosis: A Narrative Review. Schizophr Bull. 2017; 43(2): 287– 92. 10.1093/schbul/sbw180 28053019 PMC5782499 · DOI
  5. [6]Howes OD, McCutcheon R, Owen MJ, Murray RM. The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia. Biol Psychiatry. 2017; 81(1): 9– 20. 10.1016/j.biopsych.2016.07.014 27720198 PMC5675052 · DOI
  6. [8]Egerton A, Valmaggia LR, Howes OD, Day F, Chaddock CA, Allen P, et al Adversity in childhood linked to elevated striatal dopamine function in adulthood. Schizophrenia research. 2016; 176(2–3): 171– 6. 10.1016/j.schres.2016.06.005 27344984 PMC5147458 · DOI · Paper page
  7. [9]Allen P, Sommer IE, Jardri R, Eysenck MW, Hugdahl K. Extrinsic and default mode networks in psychiatric conditions: Relationship to excitatory-inhibitory transmitter balance and early trauma. Neurosci Biobehav Rev. 2019; 99: 90– 100. 10.1016/j.neubiorev.2019.02.004 30769024 · DOI
  8. [10]Misiak B, Krefft M, Bielawski T, Moustafa AA, Sasiadek MM, Frydecka D. Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings. Neurosci Biobehav Rev. 2017; 75: 393– 406. 10.1016/j.neubiorev.2017.02.015 28216171 · DOI
  9. [12]Reinwald JR, Becker R, Mallien AS, Falfan-Melgoza C, Sack M, Clemm von Hohenberg C, et al Neural Mechanisms of Early-Life Social Stress as a Developmental Risk Factor for Severe Psychiatric Disorders. Biol Psychiatry. 2018; 84(2): 116– 28. 10.1016/j.biopsych.2017.12.010 29397900 · DOI
  10. [13]Levine JB, Youngs RM, MacDonald ML, Chu M, Leeder AD, Berthiaume F, et al Isolation rearing and hyperlocomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex. Neuroscience. 2007; 145(1): 42– 55. 10.1016/j.neuroscience.2006.11.063 17239545 · DOI
  11. [15]Vanderschuren LJ, Achterberg EJ, Trezza V. The neurobiology of social play and its rewarding value in rats. Neurosci Biobehav Rev. 2016; 70: 86– 105. 10.1016/j.neubiorev.2016.07.025 27587003 PMC5074863 · DOI · Paper page
  12. [19]Inta D, Vogt MA, Elkin H, Weber T, Lima-Ojeda JM, Schneider M, et al Phenotype of mice with inducible ablation of GluA1 AMPA receptors during late adolescence: relevance for mental disorders. Hippocampus. 2014; 24(4): 424– 35. 10.1002/hipo.22236 24339333 · DOI
  13. [20]Giovanoli S, Engler H, Engler A, Richetto J, Voget M, Willi R, et al Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science. 2013; 339(6123): 1095– 9. 10.1126/science.1228261 23449593 · DOI · Paper page
  14. [21]Calabrese F, Brivio P, Gruca P, Lason-Tyburkiewicz M, Papp M, Riva MA. Chronic Mild Stress-Induced Alterations of Local Protein Synthesis: A Role for Cognitive Impairment. ACS Chem Neurosci. 2017; 8(4): 817– 25. 10.1021/acschemneuro.6b00392 28094500 · DOI
  15. [22]Luoni A, Macchi F, Papp M, Molteni R, Riva MA. Lurasidone exerts antidepressant properties in the chronic mild stress model through the regulation of synaptic and neuroplastic mechanisms in the rat prefrontal cortex. Int J Neuropsychopharmacol. 2014; 18(4). PMC4360224 25522402
  16. [25]Tulogdi A, Toth M, Barsvari B, Biro L, Mikics E, Haller J. Effects of resocialization on post-weaning social isolation-induced abnormal aggression and social deficits in rats. Developmental psychobiology. 2014; 56(1): 49– 57. 10.1002/dev.21090 23168609 · DOI
  17. [27]Wongwitdecha N, Marsden CA. Social isolation increases aggressive behaviour and alters the effects of diazepam in the rat social interaction test. Behav Brain Res. 1996; 75(1–2): 27– 32. 10.1016/0166-4328(96)00181-7 8800657 · DOI
  18. [28]Holson RR, Scallet AC, Ali SF, Turner BB. "Isolation stress" revisited: isolation-rearing effects depend on animal care methods. Physiol Behav. 1991; 49(6): 1107– 18. 10.1016/0031-9384(91)90338-o 1896492 · DOI · Paper page
  19. [29]Deacon RM, Raley JM, Perry VH, Rawlins JN. Burrowing into prion disease. Neuroreport. 2001; 12(9): 2053– 7. 10.1097/00001756-200107030-00052 11435945 · DOI
  20. [30]Jirkof P. Burrowing and nest building behavior as indicators of well-being in mice. J Neurosci Methods. 2014; 234: 139– 46. 10.1016/j.jneumeth.2014.02.001 24525328 · DOI
  21. [31]Teeling JL, Felton LM, Deacon RM, Cunningham C, Rawlins JN, Perry VH. Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines. Brain Behav Immun. 2007; 21(6): 836– 50. 10.1016/j.bbi.2007.01.012 17367989 · DOI
  22. [32]Deacon RM. Burrowing in rodents: a sensitive method for detecting behavioral dysfunction. Nat Protoc. 2006; 1(1): 118– 21. 10.1038/nprot.2006.19 17406222 · DOI
  23. [33]Deacon RM. Burrowing: a sensitive behavioural assay, tested in five species of laboratory rodents. Behav Brain Res. 2009; 200(1): 128– 33. 10.1016/j.bbr.2009.01.007 19373978 · DOI
  24. [34]Strekalova T, Steinbusch HW. Measuring behavior in mice with chronic stress depression paradigm. Progress in neuro-psychopharmacology & biological psychiatry. 2010; 34(2): 348– 61. 20026369
  25. [35]Andrews N, Legg E, Lisak D, Issop Y, Richardson D, Harper S, et al Spontaneous burrowing behaviour in the rat is reduced by peripheral nerve injury or inflammation associated pain. Eur J Pain. 2012; 16(4): 485– 95. 10.1016/j.ejpain.2011.07.012 22396078 · DOI
  26. [36]Koska I, van Dijk RM, Seiffert I, Di Liberto V, Moller C, Palme R, et al Toward evidence-based severity assessment in rat models with repeated seizures: II. Chemical post-status epilepticus model. Epilepsia. 2019; 60(10): 2114– 27. 10.1111/epi.16330 31471910 · DOI
  27. [37]King MV, Seeman P, Marsden CA, Fone KC. Increased dopamine D2High receptors in rats reared in social isolation. Synapse. 2009; 63(6): 476– 83. 10.1002/syn.20624 19217027 · DOI
  28. [38]Harte MK, Powell SB, Swerdlow NR, Geyer MA, Reynolds GP. Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats. J Neural Transm (Vienna). 2007; 114(7): 893– 8. 10.1007/s00702-007-0627-6 17594127 · DOI
  29. [39]Silva-Gomez AB, Rojas D, Juarez I, Flores G. Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats. Brain Res. 2003; 983(1–2): 128– 36. 10.1016/s0006-8993(03)03042-7 12914973 · DOI · Paper page
  30. [40]Lu L, Bao G, Chen H, Xia P, Fan X, Zhang J, et al Modification of hippocampal neurogenesis and neuroplasticity by social environments. Exp Neurol. 2003; 183(2): 600– 9. 10.1016/s0014-4886(03)00248-6 14552901 · DOI
  31. [41]Roberts L, Greene JR. Post-weaning social isolation of rats leads to a diminution of LTP in the CA1 to subiculum pathway. Brain Res. 2003; 991(1–2): 271– 3. 10.1016/j.brainres.2003.08.022 14575904 · DOI
  32. [42]Preece MA, Dalley JW, Theobald DE, Robbins TW, Reynolds GP. Region specific changes in forebrain 5-hydroxytryptamine1A and 5-hydroxytryptamine2A receptors in isolation-reared rats: an in vitro autoradiography study. Neuroscience. 2004; 123(3): 725– 32. 10.1016/j.neuroscience.2003.10.008 14706784 · DOI
  33. [43]Filipovic D, Stanisavljevic A, Jasnic N, Bernardi RE, Inta D, Peric I, et al Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus. Neuroscience. 2018; 371: 384– 94. 10.1016/j.neuroscience.2017.12.020 29275206 · DOI
  34. [44]Mora F, Segovia G, Del Arco A, de Blas M, Garrido P. Stress, neurotransmitters, corticosterone and body-brain integration. Brain Res. 2012; 1476: 71– 85. 10.1016/j.brainres.2011.12.049 22285436 · DOI · Paper page
  35. [46]Shinohara R, Taniguchi M, Ehrlich AT, Yokogawa K, Deguchi Y, Cherasse Y, et al Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice. Mol Psychiatry. 2018; 23(8): 1717– 30. 10.1038/mp.2017.177 28924188 · DOI
  36. [47]Murinova J, Hlavacova N, Chmelova M, Riecansky I. The Evidence for Altered BDNF Expression in the Brain of Rats Reared or Housed in Social Isolation: A Systematic Review. Frontiers in behavioral neuroscience. 2017; 11: 101 10.3389/fnbeh.2017.00101 28620285 PMC5449742 · DOI · Paper page
  37. [48]Filipovic D, Todorovic N, Bernardi RE, Gass P. Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms. Brain structure & function. 2017; 222(1): 1– 20. 27033097
  38. [49]Di Liberto V, van Dijk RM, Brendel M, Waldron AM, Moller C, Koska I, et al Imaging correlates of behavioral impairments: An experimental PET study in the rat pilocarpine epilepsy model. Neurobiol Dis. 2018; 118: 9– 21. 10.1016/j.nbd.2018.06.010 29933054 · DOI
  39. [50]Zueger M, Urani A, Chourbaji S, Zacher C, Roche M, Harkin A, et al Olfactory bulbectomy in mice induces alterations in exploratory behavior. Neurosci Lett. 2005; 374(2): 142– 6. 10.1016/j.neulet.2004.10.040 15644281 · DOI
  40. [51]Richter SH, Garner JP, Zipser B, Lewejohann L, Sachser N, Touma C, et al Effect of population heterogenization on the reproducibility of mouse behavior: a multi-laboratory study. PLoS One. 2011; 6(1): e16461 10.1371/journal.pone.0016461 21305027 PMC3031565 · DOI
  41. [52]Bates DM, Martin; Bolker, Ben; Walker, Steve. Fitting Linear Mixed-Effects Models Using lme4. Journal of Statistical Software. 2015; 67(1): 1– 48.
  42. [55]Guilloux JP, Seney M, Edgar N, Sibille E. Integrated behavioral z-scoring increases the sensitivity and reliability of behavioral phenotyping in mice: relevance to emotionality and sex. J Neurosci Methods. 2011; 197(1): 21– 31. 10.1016/j.jneumeth.2011.01.019 21277897 PMC3086134 · DOI
  43. [56]Gentsch C, Lichtsteiner M, Frischknecht HR, Feer H, Siegfried B. Isolation-induced locomotor hyperactivity and hypoalgesia in rats are prevented by handling and reversed by resocialization. Physiol Behav. 1988; 43(1): 13– 6. 10.1016/0031-9384(88)90091-1 3413245 · DOI
  44. [57]Geyer MA, Wilkinson LS, Humby T, Robbins TW. Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biol Psychiatry. 1993; 34(6): 361– 72. 10.1016/0006-3223(93)90180-l 8218603 · DOI
  45. [58]Weiss IC, Di Iorio L, Feldon J, Domeney AM. Strain differences in the isolation-induced effects on prepulse inhibition of the acoustic startle response and on locomotor activity. Behav Neurosci. 2000; 114(2): 364– 73. 10832797
  46. [59]van den Berg CL, Hol T, Van Ree JM, Spruijt BM, Everts H, Koolhaas JM. Play is indispensable for an adequate development of coping with social challenges in the rat. Developmental psychobiology. 1999; 34(2): 129– 38. 10086231
  47. [60]Lukkes J, Vuong S, Scholl J, Oliver H, Forster G. Corticotropin-releasing factor receptor antagonism within the dorsal raphe nucleus reduces social anxiety-like behavior after early-life social isolation. J Neurosci. 2009; 29(32): 9955– 60. 10.1523/JNEUROSCI.0854-09.2009 19675229 PMC2772211 · DOI
  48. [61]Lukkes JL, Mokin MV, Scholl JL, Forster GL. Adult rats exposed to early-life social isolation exhibit increased anxiety and conditioned fear behavior, and altered hormonal stress responses. Horm Behav. 2009; 55(1): 248– 56. 10.1016/j.yhbeh.2008.10.014 19027017 · DOI
  49. [62]Mikics E, Guirado R, Umemori J, Toth M, Biro L, Miskolczi C, et al Social Learning Requires Plasticity Enhanced by Fluoxetine Through Prefrontal Bdnf-TrkB Signaling to Limit Aggression Induced by Post-Weaning Social Isolation. Neuropsychopharmacology. 2018; 43(2): 235– 45. 10.1038/npp.2017.142 28685757 PMC5635971 · DOI
  50. [63]Seffer D, Rippberger H, Schwarting RK, Wohr M. Pro-social 50-kHz ultrasonic communication in rats: post-weaning but not post-adolescent social isolation leads to social impairments-phenotypic rescue by resocialization. Frontiers in behavioral neuroscience. 2015; 9: 102 10.3389/fnbeh.2015.00102 25983681 PMC4416445 · DOI
  51. [64]Wright IK, Upton N, Marsden CA. Resocialisation of isolation-reared rats does not alter their anxiogenic profile on the elevated X-maze model of anxiety. Physiol Behav. 1991; 50(6): 1129– 32. 10.1016/0031-9384(91)90572-6 1798767 · DOI · Paper page
  52. [65]Vale AL, Montgomery AM. Social interaction: responses to chlordiazepoxide and the loss of isolation-reared effects with paired-housing. Psychopharmacology (Berl). 1997; 133(2): 127– 32. 10.1007/s002130050382 9342778 · DOI
  53. [66]Kokare DM, Dandekar MP, Singru PS, Gupta GL, Subhedar NK. Involvement of alpha-MSH in the social isolation induced anxiety- and depression-like behaviors in rat. Neuropharmacology. 2010; 58(7): 1009– 18. 10.1016/j.neuropharm.2010.01.006 20080115 · DOI
  54. [67]Meng Q, Li N, Han X, Shao F, Wang W. Peri-adolescence isolation rearing alters social behavior and nociception in rats. Neurosci Lett. 2010; 480(1): 25– 9. 10.1016/j.neulet.2010.05.067 20638959 · DOI
  55. [69]Leal G, Comprido D, Duarte CB. BDNF-induced local protein synthesis and synaptic plasticity. Neuropharmacology. 2014; 76 Pt C: 639– 56. 23602987
  56. [70]Begni V, Riva MA, Cattaneo A. Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions. Clin Sci (Lond). 2017; 131(2): 123– 38. 28011898
  57. [71]Bennett MR, Lagopoulos J. Stress and trauma: BDNF control of dendritic-spine formation and regression. Prog Neurobiol. 2014; 112: 80– 99. 10.1016/j.pneurobio.2013.10.005 24211850 · DOI · Paper page
  58. [72]Cattaneo A, Cattane N, Begni V, Pariante CM, Riva MA. The human BDNF gene: peripheral gene expression and protein levels as biomarkers for psychiatric disorders. Translational psychiatry. 2016; 6(11): e958 10.1038/tp.2016.214 27874848 PMC5314126 · DOI · Paper page
  59. [73]An JJ, Gharami K, Liao GY, Woo NH, Lau AG, Vanevski F, et al Distinct role of long 3' UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell. 2008; 134(1): 175– 87. 10.1016/j.cell.2008.05.045 18614020 PMC2527207 · DOI
  60. [74]Baj G, Leone E, Chao MV, Tongiorgi E. Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments. Proc Natl Acad Sci U S A. 2011; 108(40): 16813– 8. 10.1073/pnas.1014168108 21933955 PMC3189043 · DOI
  61. [75]Rousseaud A, Delepine C, Nectoux J, Billuart P, Bienvenu T. Differential Expression and Regulation of Brain-Derived Neurotrophic Factor (BDNF) mRNA Isoforms in Brain Cells from Mecp2(308/y) Mouse Model. J Mol Neurosci. 2015; 56(4): 758– 67. 10.1007/s12031-014-0487-0 25634725 · DOI
  62. [76]Perovic M, Tesic V, Mladenovic Djordjevic A, Smiljanic K, Loncarevic-Vasiljkovic N, Ruzdijic S, et al BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. Age (Dordr). 2013; 35(6): 2057– 70. 23255148 PMC3824987
  63. [77]Wall VL, Fischer EK, Bland ST. Isolation rearing attenuates social interaction-induced expression of immediate early gene protein products in the medial prefrontal cortex of male and female rats. Physiol Behav. 2012; 107(3): 440– 50. 10.1016/j.physbeh.2012.09.002 22982514 PMC4529065 · DOI · Paper page
  64. [78]Li M, Du W, Shao F, Wang W. Cognitive dysfunction and epigenetic alterations of the BDNF gene are induced by social isolation during early adolescence. Behav Brain Res. 2016; 313: 177– 83. 10.1016/j.bbr.2016.07.025 27435421 · DOI · Paper page
  65. [79]Adzic M, Djordjevic J, Djordjevic A, Niciforovic A, Demonacos C, Radojcic M, et al Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain. The Journal of endocrinology. 2009; 202(1): 87– 97. 10.1677/JOE-08-0509 19406955 PMC2695659 · DOI
  66. [80]Reinhart V, Bove SE, Volfson D, Lewis DA, Kleiman RJ, Lanz TA. Evaluation of TrkB and BDNF transcripts in prefrontal cortex, hippocampus, and striatum from subjects with schizophrenia, bipolar disorder, and major depressive disorder. Neurobiol Dis. 2015; 77: 220– 7. 10.1016/j.nbd.2015.03.011 25796564 · DOI
  67. [81]Steward O, Farris S, Pirbhoy PS, Darnell J, Driesche SJ. Localization and local translation of Arc/Arg3.1 mRNA at synapses: some observations and paradoxes. Frontiers in molecular neuroscience. 2014; 7: 101 10.3389/fnmol.2014.00101 25628532 PMC4290588 · DOI
  68. [82]Nikolaienko O, Patil S, Eriksen MS, Bramham CR. Arc protein: a flexible hub for synaptic plasticity and cognition. Seminars in cell & developmental biology. 2018; 77: 33– 42. 28890419
  69. [83]Pisu MG, Dore R, Mostallino MC, Loi M, Pibiri F, Mameli R, et al Down-regulation of hippocampal BDNF and Arc associated with improvement in aversive spatial memory performance in socially isolated rats. Behav Brain Res. 2011; 222(1): 73– 80. 10.1016/j.bbr.2011.03.021 21420441 · DOI
  70. [84]Ieraci A, Mallei A, Popoli M. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice. Neural Plast. 2016; 2016: 6212983 10.1155/2016/6212983 26881124 PMC4736811 · DOI
  71. [85]Kim E, Sheng M. PDZ domain proteins of synapses. Nat Rev Neurosci. 2004; 5(10): 771– 81. 10.1038/nrn1517 15378037 · DOI
  72. [86]Zeng M, Shang Y, Araki Y, Guo T, Huganir RL, Zhang M. Phase Transition in Postsynaptic Densities Underlies Formation of Synaptic Complexes and Synaptic Plasticity. Cell. 2016; 166(5): 1163– 75 e12. 10.1016/j.cell.2016.07.008 27565345 PMC5564291 · DOI
  73. [87]Ohnuma T, Kato H, Arai H, Faull RL, McKenna PJ, Emson PC. Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia. Neuroreport. 2000; 11(14): 3133– 7. 10.1097/00001756-200009280-00019 11043537 · DOI
  74. [88]Coley AA, Gao WJ. PSD95: A synaptic protein implicated in schizophrenia or autism? Progress in neuro-psychopharmacology & biological psychiatry. 2018; 82: 187– 94. 29169997 PMC5801047
  75. [91]Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA. Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Archives of general psychiatry. 2000; 57(3): 237– 45. 10.1001/archpsyc.57.3.237 10711910 · DOI · Paper page
  76. [92]Filipovic D, Zlatkovic J, Gass P, Inta D. The differential effects of acute vs. chronic stress and their combination on hippocampal parvalbumin and inducible heat shock protein 70 expression. Neuroscience. 2013; 236: 47– 54. 10.1016/j.neuroscience.2013.01.033 23352936 · DOI
  77. [93]Bagalkot TR, Jin HM, Prabhu VV, Muna SS, Cui Y, Yadav BK, et al Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice. Neuroscience. 2015 12 17; 311: 444– 52. 10.1016/j.neuroscience.2015.10.024 Epub 2015 Oct 17.. 26484605 · DOI
  78. [94]Tomas-Roig J, Havemann-Reinecke U. Gene expression signature in brain regions exposed to long-term psychosocial stress following acute challenge with cannabinoid drugs. Psychoneuroendocrinology. 2019 4; 102: 1– 8. 10.1016/j.psyneuen.2018.11.023 Epub 2018 Nov 20.. 30476795 · DOI
  79. [95]Abdelrahman A, Kumstel S, Zhang X, Liebig M, Wendt EHU, Eichberg J, et al A novel multi-parametric analysis of non-invasive methods to assess animal distress during chronic pancreatitis. Sci Rep. 2019; 9(1): 14084 10.1038/s41598-019-50682-3 31575986 PMC6773730 · DOI
  80. [96]Kumstel S, Wendt EHU, Eichberg J, Talbot SR, Hager C, Zhang X, et al Grading animal distress and side effects of therapies. Ann N Y Acad Sci. 2020. 32207155
  81. [97]van Dijk RM, Koska I, Bleich A, Tolba R, Seiffert I, Moller C, et al Design of composite measure schemes for comparative severity assessment in animal-based neuroscience research: A case study focussed on rat epilepsy models. PLoS One. 2020; 15(5): e0230141 10.1371/journal.pone.0230141 32413036 PMC7228039 · DOI

Cited by

Sorted by citations

Authors
Begni, V., Sanson, A., Pfeiffer, N., Brandwein, C., Inta, D., Talbot, S. R., Riva, M. A., Gass, P., & Mallien, A. S.
Affiliations
  • University of Milan (IT)
  • Heidelberg University (DE)
  • Medizinische Hochschule Hannover (DE)
Corresponding author
Gass, Peter
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2020-10-27
Volume
15
Issue
10
Pages
e0240439
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0240439
PMC
PMC7591026
OpenAlex
W3096417670
Cited by
78
References
14
Citations by year
2026: 8 · 2025: 13 · 2024: 15 · 2023: 19 · 2022: 13 · 2021: 10
FWCI
6.07
Type
journal article
Language
en
Update notices
correction (2021-02-26)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • DFG (Forschergruppe 2591, P05)
  • Italian Ministry of University and Research (PRIN 2017AY8BP4, PON "Ricerca e Innovazione" PerMedNet project ARS01_01226)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Veterinary › Small Animals › Animal Behavior and Welfare Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
social isolation, early life stress, animal welfare, 3Rs, resocialization, hyperactivity, neuroplasticity, prefrontal cortex, Arc, dopamine receptors, burrowing behavior
MeSH terms
Animals, Animal Welfare, Behavior, Animal, Brain, Cytoskeletal Proteins, Genetic Markers, Glutamate Decarboxylase, Nerve Tissue Proteins, Neuronal Plasticity, Phenotype, Social Isolation, Stress, Psychological, Brain-Derived Neurotrophic Factor, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review