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Favre MR, La Mendola D, Meystre J, et al. Predictable enriched environment prevents development of hyper-emotionality in the VPA rat model of autism. Front Neurosci. 2015;9:127doi: 10.3389/fnins.2015.00127.
Favre, M. R., La Mendola, D., Meystre, J., Christodoulou, D., Cochrane, M. J., Markram, H., & Markram, K. (2015). Predictable enriched environment prevents development of hyper-emotionality in the VPA rat model of autism. Frontiers in neuroscience, 9127. https://doi.org/10.3389/fnins.2015.00127
Favre, Mônica R, et al. "Predictable enriched environment prevents development of hyper-emotionality in the VPA rat model of autism." Frontiers in neuroscience vol. 9 (2015): 127. doi: https://doi.org/10.3389/fnins.2015.00127
Favre MR, La Mendola D, Meystre J, Christodoulou D, Cochrane MJ, Markram H, Markram K. Predictable enriched environment prevents development of hyper-emotionality in the VPA rat model of autism. Front Neurosci. 2015 Jun 02;9:127. doi: 10.3389/fnins.2015.00127. eCollection 2015. PMID: 26089770; PMCID: PMC4452729.
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Front Neurosci. 2015 Jun 02;9:127. doi: 10.3389/fnins.2015.00127. eCollection 2015.

Predictable enriched environment prevents development of hyper-emotionality in the VPA rat model of autism.

Frontiers in neuroscience

Mônica R Favre, Deborah La Mendola, Julie Meystre, Dimitri Christodoulou, Melissa J Cochrane, Henry Markram, Kamila Markram

Affiliations

  1. Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.

PMID: 26089770 PMCID: PMC4452729 DOI: 10.3389/fnins.2015.00127

Abstract

Understanding the effects of environmental stimulation in autism can improve therapeutic interventions against debilitating sensory overload, social withdrawal, fear and anxiety. Here, we evaluate the role of environmental predictability on behavior and protein expression, and inter-individual differences, in the valproic acid (VPA) model of autism. Male rats embryonically exposed (E11.5) either to VPA, a known autism risk factor in humans, or to saline, were housed from weaning into adulthood in a standard laboratory environment, an unpredictably enriched environment, or a predictably enriched environment. Animals were tested for sociability, nociception, stereotypy, fear conditioning and anxiety, and for tissue content of glutamate signaling proteins in the primary somatosensory cortex, hippocampus and amygdala, and of corticosterone in plasma, amygdala and hippocampus. Standard group analyses on separate measures were complemented with a composite emotionality score, using Cronbach's Alpha analysis, and with multivariate profiling of individual animals, using Hierarchical Cluster Analysis. We found that predictable environmental enrichment prevented the development of hyper-emotionality in the VPA-exposed group, while unpredictable enrichment did not. Individual variation in the severity of the autistic-like symptoms (fear, anxiety, social withdrawal and sensory abnormalities) correlated with neurochemical profiles, and predicted their responsiveness to predictability in the environment. In controls, the association between socio-affective behaviors, neurochemical profiles and environmental predictability was negligible. This study suggests that rearing in a predictable environment prevents the development of hyper-emotional features in animals exposed to an autism risk factor, and demonstrates that unpredictable environments can lead to negative outcomes, even in the presence of environmental enrichment.

Keywords: autism; emotion; environmental enrichment; individual differences; predictability; protein expression; rat; valproic acid

References

  1. Brain Res. 2011 Mar 22;1380:42-77 - PubMed
  2. Pediatr Res. 2011 May;69(5 Pt 2):92R-100R - PubMed
  3. Int J Psychophysiol. 2012 Feb;83(2):240-7 - PubMed
  4. Neurotoxicol Teratol. 2013 Mar-Apr;36:47-56 - PubMed
  5. Eur Psychiatry. 2014 Jan;29(1):11-9 - PubMed
  6. J Autism Dev Disord. 1982 Jun;12(2):185-93 - PubMed
  7. J Neurosci. 2011 Sep 14;31(37):13097-109 - PubMed
  8. Mol Autism. 2013 Sep 04;4(1):31 - PubMed
  9. Prog Neurobiol. 1990;34(4):343-54 - PubMed
  10. Front Cell Neurosci. 2014 Jan 31;8:23 - PubMed
  11. Brain Res. 2009 Oct 13;1293:129-41 - PubMed
  12. Brain Res Bull. 2012 Apr 10;87(6):556-63 - PubMed
  13. Trends Neurosci. 2011 Apr;34(4):165-76 - PubMed
  14. Ann Clin Psychiatry. 2009 Oct-Dec;21(4):213-36 - PubMed
  15. J Comp Neurol. 1996 Jun 24;370(2):247-61 - PubMed
  16. Brain Res. 2013 Aug 14;1526:15-25 - PubMed
  17. Neuropsychopharmacology. 2008 Mar;33(4):901-12 - PubMed
  18. J Autism Dev Disord. 1980 Mar;10(1):51-7 - PubMed
  19. Dev Psychopathol. 2011 Feb;23(1):1-5 - PubMed
  20. Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15220-5 - PubMed
  21. Front Hum Neurosci. 2010 Dec 21;4:224 - PubMed
  22. ILAR J. 2005;46(2):140-7 - PubMed
  23. Nat Rev Neurosci. 2000 Dec;1(3):191-8 - PubMed
  24. Reprod Toxicol. 1997 Mar-Jun;11(2-3):417-22 - PubMed
  25. Cereb Cortex. 2008 Apr;18(4):763-70 - PubMed
  26. Psychopharmacology (Berl). 1984;83(4):390-6 - PubMed
  27. J Autism Dev Disord. 2006 Jan;36(1):27-43 - PubMed
  28. Neurosci Res. 2009 Jun;64(2):162-9 - PubMed
  29. Neuropathol Appl Neurobiol. 2014 Feb;40(1):13-25 - PubMed
  30. Neurotoxicol Teratol. 2013 Mar-Apr;36:57-66 - PubMed
  31. J Autism Dev Disord. 2006 Aug;36(6):779-93 - PubMed
  32. Curr Pharm Des. 2013;19(28):5043-50 - PubMed
  33. J Toxicol Sci. 2013;38(3):391-402 - PubMed
  34. Dialogues Clin Neurosci. 2009;11(1):35-43 - PubMed
  35. J Neurochem. 2013 Mar;124(6):832-43 - PubMed
  36. Mol Neurobiol. 2014 Feb;49(1):512-28 - PubMed
  37. Brain Res. 2011 Mar 22;1380:138-45 - PubMed
  38. Neuropharmacology. 2013 Jan;64:515-28 - PubMed
  39. J Am Acad Child Adolesc Psychiatry. 2012 Apr;51(4):356-67 - PubMed
  40. Lancet. 2014 Mar 8;383(9920):896-910 - PubMed
  41. Curr Top Behav Neurosci. 2011;7:187-212 - PubMed
  42. Front Behav Neurosci. 2013 Dec 06;7:190 - PubMed
  43. Mol Cell Neurosci. 2014 Mar;59:57-62 - PubMed
  44. Eur Neuropsychopharmacol. 2012;22 Suppl 3:S487-91 - PubMed
  45. Front Neurosci. 2007 Oct 15;1(1):77-96 - PubMed
  46. Neuropsychopharmacology. 2006 Jan;31(1):36-46 - PubMed
  47. J Endocrinol. 2011 May;209(2):153-67 - PubMed
  48. Front Integr Neurosci. 2012 Dec 04;6:113 - PubMed
  49. Behav Neurosci. 2013 Aug;127(4):487-97 - PubMed
  50. Pediatr Clin North Am. 2012 Feb;59(1):147-64, xi-xii - PubMed
  51. Biol Psychiatry. 2009 Feb 1;65(3):191-7 - PubMed
  52. Front Hum Neurosci. 2013 Jul 25;7:417 - PubMed
  53. J Med Genet. 1995 Sep;32(9):724-7 - PubMed
  54. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13501-6 - PubMed
  55. Arch Neurol. 2010 Apr;67(4):395-9 - PubMed
  56. Behav Brain Res. 2013 Aug 15;251:41-9 - PubMed
  57. Front Synaptic Neurosci. 2009 Jun 24;1:1 - PubMed
  58. Neurotherapeutics. 2010 Jul;7(3):232-40 - PubMed
  59. Front Hum Neurosci. 2013 Sep 27;7:609 - PubMed
  60. JAMA. 2013 Apr 24;309(16):1696-703 - PubMed
  61. Rev Bras Psiquiatr. 2013;35 Suppl 1:S62-72 - PubMed
  62. Int J Dev Neurosci. 2005 Apr-May;23(2-3):189-99 - PubMed
  63. Front Neural Circuits. 2008 Oct 29;2:4 - PubMed
  64. Nat Rev Neurosci. 2013 Feb;14(2):97-111 - PubMed
  65. Front Behav Neurosci. 2013 Jul 24;7:88 - PubMed
  66. Clin Psychol Rev. 2009 Apr;29(3):216-29 - PubMed
  67. Pharmacol Biochem Behav. 2012 Feb;100(4):841-9 - PubMed
  68. Front Pediatr. 2014 Jun 20;2:58 - PubMed

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