Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-27T19:56:19.186Z Has data issue: false hasContentIssue false
  • English
  • Français

Recent advances in animal model experimentation in autism research

Published online by Cambridge University Press:  15 November 2013

Mousumi Tania ,
Md. Asaduzzaman Khan  and
Kun Xia
Mousumi Tania
Affiliation:
State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China Department of Biochemistry, School of Life Sciences, Central South University, Changsha, Hunan, China
Md. Asaduzzaman Khan
Affiliation:
Department of Biochemistry, School of Life Sciences, Central South University, Changsha, Hunan, China Research Center for Preclinical Medicine, Luzhou Medical College, Luzhou, Sichuan, China
Kun Xia*
Affiliation:
State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China
*
Kun Xia, State Key Laboratory of Medical Genetics, Central South University, Changsha City, Hunan, China. Tel: +86 731 84805357; Fax: +86 731 84478152; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Autism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.

Methods

We have reviewed the publications over the last three decades, which are related to animal model study in autism.

Results

Animal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.

Conclusion

In this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

Keywords

animal modelautismgenetic manipulationstranslational research
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 26 , Issue 5 , October 2014 , pp. 264 - 271
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Klauck, SM. Genetics of autism spectrum disorder. Eur J Hum Genet 2006;14:714–720.CrossRefGoogle ScholarPubMed
2.Myers, SM, Johnson, CP. Council on Children with Disabilities. Management of children with autism spectrum disorders. Pediatrics 2007;120:1162–1182.Google Scholar
3.Newschaffer, CJ, Croen, LA, Daniels, Jet al. The epidemiology of autism spectrum disorders. Annu Rev Public Health 2007;28:235–258.Google Scholar
4.Wing, L, Potter, D. The epidemiology of autistic spectrum disorders: is the prevalence rising? Ment Retard Dev Disabil Res Rev 2002;8:151–161.Google Scholar
5.Fombonne, E. Epidemiology of pervasive developmental disorders. Pediatr Res 2009;65:591–598.CrossRefGoogle ScholarPubMed
6.Howlin, P. Practitioner review: psychological and educational treatments for autism. J Child Psychol Psychiatry 1998;39:307–322.Google Scholar
7.Montes, G, Halterman, JS. Child care problems and employment among families with preschool-aged children with autism in the United States. Pediatrics 2008;122:e202–e208.Google Scholar
8.Shastry, BS. Molecular genetics of autism spectrum disorders. J Hum Genet 2003;48:495–501.Google Scholar
9.Nomura, J, Takumi, T. Animal models of psychiatric disorders that reflect human copy number variation. Neural Plast 2012;2012:589524.Google Scholar
10.Cook, EH, Scherer, SW. Copy-number variations associated with neuropsychiatric conditions. Nature 2008;455:919–923.Google Scholar
11.Landrigan, PJ. What causes autism? Exploring the environmental contribution. Curr Opin Pediatr 2010;22:219–225.Google Scholar
12.Courchesne, E, Pierce, K, Schumann, CMet al. Mapping early brain development in autism. Neuron 2007;56:399–413.Google Scholar
13.Chomiak, T, Hu, B. Alterations of neocortical development and maturation in autism: insight from valproic acid exposure and animal models of autism. Neurotoxicol Teratol 2013;36:57–66.Google Scholar
14.Smile, S, Anagnostou, E. New models for considering the role of medication in the treatment and elucidation of the etiology of autism. Curr Psychiatry Rep 2012;14:726–731.CrossRefGoogle ScholarPubMed
15.Meyza, KZ, Defensor, EB, Jensen, ALet al. The BTBR T(+)tf/J mouse model for autism spectrum disorders-in search of biomarkers. Behav Brain Res 2013;251:25–34.Google Scholar
16.Watson, KK, Platt, ML. Of mice and monkeys: using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders. J Neurodev Disord 2012;4:21.Google Scholar
17.Crawley, JN. Designing mouse behavioral tasks relevant to autistic-like behaviors. Ment Retard Dev Disabil Res Rev 2004;10:248–258.Google Scholar
18.Nestler, EJ, Hyman, SE. Animal models of neuropsychiatric disorders. Nat Neurosci 2010;3:1161–1169.Google Scholar
19.Dantzer, R, Kelley, KW. Autistic children: a neuroimmune perspective. Brain Behav Immun 2008;22:804–805.Google Scholar
20.Silverman, JL, Babineau, BA, Oliver, CF, Karras, MN, Crawley, JN. Influence of stimulant-induced hyperactivity on social approach in the BTBR mouse model of autism. Neuropharmacology 2013;68:210–222.Google Scholar
21.Ey, E, Leblond, CS, Bourgeron, T. Behavioral profiles of mouse models for autism spectrum disorders. Autism Res 2011;4:5–16.CrossRefGoogle ScholarPubMed
22.Roullet, FI, Wollaston, L, Decatanzaro, D, Foster, JA. Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid. Neuroscience 2010;170:514–522.Google Scholar
23.Lukose, R, Schmidt, E, Wolski, TP Jr, Murawski, NJ, Kulesza, RJ Jr. Malformation of the superior olivary complex in an animal model of autism. Brain Res 2011;398:102–112.Google Scholar
24.Bambini-Junior, V, Rodrigues, L, Behr, GA, Moreira, JC, Riesgo, R, Gottfried, C. Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parameters. Brain Res 2011;1408:8–16.Google Scholar
25.Kim, KC, Kim, P, Go, HSet al. The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats. Toxicol Lett 2011;201:137–142.CrossRefGoogle ScholarPubMed
26.Mychasiuk, R, Richards, S, Nakahashi, A, Kolb, B, Gibb, R. Effects of rat prenatal exposure to valproic acid on behaviour and neuro-anatomy. Dev Neurosci 2012;34:268–276.Google Scholar
27.Kim, KC, Kim, P, Go, HSet al. Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder. J Neurochem 2013;124:832–843.CrossRefGoogle ScholarPubMed
28.Favre, MR, Barkat, TR, Lamendola, D, Khazen, G, Markram, H, Markram, K. General developmental health in the VPA-rat model of autism. Front Behav Neurosci 2013;7:88.Google Scholar
29.Go, HS, Kim, KC, Choi, CSet al. Prenatal exposure to valproic acid increases the neural progenitor cell pool and induces macrocephaly in rat brain via a mechanism involving the GSK-3β/β-catenin pathway. Neuropharmacology 2012;63:1028–1041.CrossRefGoogle Scholar
30.Zhang, Y, Sun, Y, Wang, F, Wang, Z, Peng, Y, Li, R. Downregulating the canonical Wnt/β-catenin signaling pathway attenuates the susceptibility to autism-like phenotypes by decreasing oxidative stress. Neurochem Res 2012;37:1409–1419.Google Scholar
31.Shultz, SR, Macfabe, DF, Martin, Set al. Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impairs cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism. Behav Brain Res 2009;200:33–41.Google Scholar
32.MacFabe, DF, Cain, NE, Boon, F, Ossenkopp, KP, Cain, DP. Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: relevance to autism spectrum disorder. Behav Brain Res 2011;217:47–54.Google Scholar
33.El-Ansary, AK, Ben Bacha, A, Kotb, M. Etiology of autistic features: the persisting neurotoxic effects of propionic acid. J Neuroinflam 2012;9:74.Google Scholar
34.Baudouin, SJ, Gaudias, J, Gerharz, Set al. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science 2012;338:128–132.CrossRefGoogle ScholarPubMed
35.Chadman, KK, Gong, S, Scattoni, MLet al. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res 2008;1:147–158.Google Scholar
36.Hunter, JW, Mullen, GP, McManus, JR, Heatherly, JM, Duke, A, Rand, JB. Neuroligin-deficient mutants of C. elegans have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity. Dis Model Mech 2010;3:366–376.Google Scholar
37.Ellegood, J, Lerch, JP, Henkelman, RM. Brain abnormalities in a neuroligin3 R451C knockin mouse model associated with autism. Autism Res 2011;4:368–376.Google Scholar
38.Fischer, J, Hammerschmidt, K. Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication. Genes Brain Behav 2011;10:17–27.Google Scholar
39.Radyushkin, K, Hammerschmidt, K, Boretius, Set al. Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav 2009;8:416–425.Google Scholar
40.Etherton, MR, Blaiss, CA, Powell, CM, Südhof, TC. Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc Natl Acad Sci USA 2009;106:17 998–18 003.Google Scholar
41.Silverman, JL, Turner, SM, Barkan, CLet al. Sociability and motor functions in Shank1 mutant mice. Brain Res 2011;1380:120–137.CrossRefGoogle ScholarPubMed
42.Won, H, Lee, HR, Gee, HYet al. Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function. Nature 2012;486:261–265.Google Scholar
43.Schmeisser, MJ, Ey, E, Wegener, Set al. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature 2012;486:255–260.Google Scholar
44.Bangash, MA, Park, JM, Melnikova, Tet al. Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism. Cell 2011;145:758–772.CrossRefGoogle Scholar
45.Deutsch, SI, Pepe, GJ, Burket, JA, Winebarger, EE, Herndon, AL, Benson, AD. D-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice. Brain Res 2012;1439:96–107.Google Scholar
46.Peca, J, Feliciano, C, Ting, JTet al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 2011;472:437–442.Google Scholar
47.Johnson, RA, Lam, M, Punzo, AMet al. 7,8-dihydroxyflavone exhibits therapeutic efficacy in a mouse model of Rett syndrome. J Appl Physiol 2012;112:704–710.Google Scholar
48.Derecki, NC, Cronk, JC, Lu, Zet al. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 2012;484:105–109.Google Scholar
49.Pearson, BL, Defensor, EB, Pobbe, RLet al. Mecp2 truncation in male mice promotes affiliative social behavior. Behav Genet 2012;2:299–312.Google Scholar
50.Bowers, JM, Konopka, G. The role of the FOXP family of transcription factors in ASD. Dis Markers 2012;33:251–260.Google Scholar
51.Fujita, E, Tanabe, Y, Momoi, MY, Momoi, T. Cntnap2 expression in the cerebellum of Foxp2 (R552H) mice, with a mutation related to speech-language disorder. Neurosci Lett 2012;6:277–280.Google Scholar
52.Peñagarikano, O, Abrahams, BS, Herman, EI. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 2011;147:235–246.Google Scholar
53.Peñagarikano, O, Geschwind, DH. What does CNTNAP2 reveal about autism spectrum disorder? Trends Mol Med 2012;18:156–163.Google Scholar
54.Jana, NR. Understanding the pathogenesis of Angelman syndrome through animal models. Neural Plast 2012;2012:710943.Google Scholar
55.Jiang, YH, Pan, Y, Zhu, Let al. Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3. PLoS One 2010;5:e12278.Google Scholar
56.Reith, RM, Way, S, McKenna, J 3rd, Haines, K, Gambello, MJ. Loss of the tuberous sclerosis complex protein tuberin causes Purkinje cell degeneration. Neurobiol Dis 2011;43:113–222.Google Scholar
57.Tsai, PT, Hull, C, Chu, Yet al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 2012;488:647–651.Google Scholar
58.Zeng, LH, Rensing, NR, Zhang, B, Gutmann, DH, Gambello, MJ, Wong, M. Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex. Hum Mol Genet 2011;20:445–454.Google Scholar
59.Carson, RP, Van Nielen, DL, Winzenburger, PA, Ess, KC. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiol Dis 2012;45:369–380.Google Scholar
60.Budziszewska, B, Lasoń, W, Steczkowska, M, Gergont, A. Value of the experiment for developmental neurology. Przegl Lek 2009;66:958–962.Google Scholar
61.Flint, J, Shifman, S. Animal models of psychiatric disease. Curr Opin Genet Dev 2008;18:235–240.Google Scholar
62.Cinque, C, Pondiki, S, Oddi, Det al. Modeling socially anhedonic syndromes: genetic and pharmacological manipulation of opioid neurotransmission in mice. Transl Psychiatry 2012;2:e155.Google Scholar
63.Piedimonte, LR, Wailes, IK, Weiner, HL. Tuberous sclerosis complex: molecular pathogenesis and animal models. Neurosurg Focus 2006;20:E4.Google Scholar