Studying Autism in Rodent Models: Reconciling Endophenotypes with Comorbidities

Overview

Journal Front Hum Neurosci

Specialty Neurology

Date 2013 Jul 31

PMID 23898259

Citations 24

Authors

Andrew Argyropoulos

Krista L Gilby

Elisa L Hill-Yardin

Affiliations

Soon will be listed here.

Abstract

Autism spectrum disorder (ASD) patients commonly exhibit a variety of comorbid traits including seizures, anxiety, aggressive behavior, gastrointestinal problems, motor deficits, abnormal sensory processing, and sleep disturbances for which the cause is unknown. These features impact negatively on daily life and can exaggerate the effects of the core diagnostic traits (social communication deficits and repetitive behaviors). Studying endophenotypes relevant to both core and comorbid features of ASD in rodent models can provide insight into biological mechanisms underlying these disorders. Here we review the characterization of endophenotypes in a selection of environmental, genetic, and behavioral rodent models of ASD. In addition to exhibiting core ASD-like behaviors, each of these animal models display one or more endophenotypes relevant to comorbid features including altered sensory processing, seizure susceptibility, anxiety-like behavior, and disturbed motor functions, suggesting that these traits are indicators of altered biological pathways in ASD. However, the study of behaviors paralleling comorbid traits in animal models of ASD is an emerging field and further research is needed to assess altered gastrointestinal function, aggression, and disorders of sleep onset across models. Future studies should include investigation of these endophenotypes in order to advance our understanding of the etiology of this complex disorder.

Citing Articles

Giftedness and atypical sexual differentiation: enhanced perceptual functioning through estrogen deficiency instead of androgen excess.

Sakaguchi K, Tawata S Front Endocrinol (Lausanne). 2024; 15:1343759.

PMID: 38752176 PMC: 11094242. DOI: 10.3389/fendo.2024.1343759.

Autistic Traits and Aggressive Behavior in Chinese College Students: A Serial Mediation Model and the Gender Difference.

Tan C, Song H, Ma S, Liu X, Zhao Y Psychol Res Behav Manag. 2024; 17:1385-1397.

PMID: 38529081 PMC: 10962467. DOI: 10.2147/PRBM.S451028.

Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies.

Yenkoyan K, Ounanian Z, Mirumyan M, Hayrapetyan L, Zakaryan N, Sahakyan R Curr Med Chem. 2023; 31(12):1485-1511.

PMID: 37888815 PMC: 11092563. DOI: 10.2174/0109298673252910230920151332.

Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder.

Zarate-Lopez D, Torres-Chavez A, Galvez-Contreras A, Gonzalez-Perez O Curr Neuropharmacol. 2023; 22(2):260-289.

PMID: 37873949 PMC: 10788883. DOI: 10.2174/1570159X22666231003121513.

Translational Magnetic Resonance Imaging in Autism Spectrum Disorder From the Mouse Model to Human.

Tsurugizawa T Front Neurosci. 2022; 16:872036.

PMID: 35585926 PMC: 9108701. DOI: 10.3389/fnins.2022.872036.

References

Markram K, Rinaldi T, La Mendola D, Sandi C, Markram H . Abnormal fear conditioning and amygdala processing in an animal model of autism. Neuropsychopharmacology. 2007; 33(4):901-12. DOI: 10.1038/sj.npp.1301453. View

Nesslinger N, Gorski J, Kurczynski T, Shapira S, Siegel-Bartelt J, Dumanski J . Clinical, cytogenetic, and molecular characterization of seven patients with deletions of chromosome 22q13.3. Am J Hum Genet. 1994; 54(3):464-72. PMC: 1918126. View

Shultz S, MacFabe D, Martin S, Jackson J, Taylor R, Boon F . Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism. Behav Brain Res. 2009; 200(1):33-41. DOI: 10.1016/j.bbr.2008.12.023. View

Racine R, Steingart M, McIntyre D . Development of kindling-prone and kindling-resistant rats: selective breeding and electrophysiological studies. Epilepsy Res. 1999; 35(3):183-95. DOI: 10.1016/s0920-1211(99)00013-3. View

Leekam S, Nieto C, Libby S, Wing L, Gould J . Describing the sensory abnormalities of children and adults with autism. J Autism Dev Disord. 2006; 37(5):894-910. DOI: 10.1007/s10803-006-0218-7. View

Bromley R, Mawer G, Clayton-Smith J, Baker G . Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology. 2008; 71(23):1923-4. DOI: 10.1212/01.wnl.0000339399.64213.1a. View

Betancur C, Sakurai T, Buxbaum J . The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders. Trends Neurosci. 2009; 32(7):402-12. PMC: 10354373. DOI: 10.1016/j.tins.2009.04.003. View

Kumar R . SHANK2 redemption: another synaptic protein for mental retardation and autism. Clin Genet. 2010; 78(6):519-21. DOI: 10.1111/j.1399-0004.2010.01530_2.x. View

Karaki S, Mitsui R, Hayashi H, Kato I, Sugiya H, Iwanaga T . Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res. 2006; 324(3):353-60. DOI: 10.1007/s00441-005-0140-x. View

10.

Geschwind D . Genetics of autism spectrum disorders. Trends Cogn Sci. 2011; 15(9):409-16. PMC: 3691066. DOI: 10.1016/j.tics.2011.07.003. View

11.

Pearson B, Pobbe R, Defensor E, Oasay L, Bolivar V, Blanchard D . Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism. Genes Brain Behav. 2010; 10(2):228-35. PMC: 3037433. DOI: 10.1111/j.1601-183X.2010.00659.x. View

12.

Latham K, Chung S, Allen P, Tavassoli T, Baron-Cohen S . Spatial localisation in autism: evidence for differences in early cortical visual processing. Mol Autism. 2013; 4(1):4. PMC: 3599959. DOI: 10.1186/2040-2392-4-4. View

13.

Blakemore S, Tavassoli T, Calo S, Thomas R, Catmur C, Frith U . Tactile sensitivity in Asperger syndrome. Brain Cogn. 2006; 61(1):5-13. DOI: 10.1016/j.bandc.2005.12.013. View

14.

Chakrabarti B, Dudbridge F, Kent L, Wheelwright S, Hill-Cawthorne G, Allison C . Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism Res. 2009; 2(3):157-77. DOI: 10.1002/aur.80. View

15.

Silverman J, Yang M, Lord C, Crawley J . Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci. 2010; 11(7):490-502. PMC: 3087436. DOI: 10.1038/nrn2851. View

16.

Gomot M, Bernard F, Davis M, Belmonte M, Ashwin C, Bullmore E . Change detection in children with autism: an auditory event-related fMRI study. Neuroimage. 2005; 29(2):475-84. DOI: 10.1016/j.neuroimage.2005.07.027. View

17.

Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K . Binding of neuroligins to PSD-95. Science. 1997; 277(5331):1511-5. DOI: 10.1126/science.277.5331.1511. View

18.

Verpelli C, Sala C . Molecular and synaptic defects in intellectual disability syndromes. Curr Opin Neurobiol. 2011; 22(3):530-6. DOI: 10.1016/j.conb.2011.09.007. View

19.

Zhang Q, Wang J, Li A, Liu H, Zhang W, Cui X . Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease. Mol Biol Rep. 2012; 40(4):2969-75. DOI: 10.1007/s11033-012-2368-3. View

20.

Shoji H, Kato K . Maternal care affects the development of maternal behavior in inbred mice. Dev Psychobiol. 2009; 51(4):345-57. DOI: 10.1002/dev.20375. View