Integrating epilepsy and other comorbidities into autism spectrum disorder research: a call for animal models

Inna S. Midzyanovskaya

Exploration of Neuroscience ›› 2026, Vol. 5 ›› Issue (1) : 1006145

PDF (2056KB)
Exploration of Neuroscience ›› 2026, Vol. 5 ›› Issue (1) :1006145 DOI: 10.37349/en.2026.1006145
research-article
Integrating epilepsy and other comorbidities into autism spectrum disorder research: a call for animal models
Author information +
History +
PDF (2056KB)

Abstract

Autism spectrum disorder (ASD) is a clinically heterogeneous neurodevelopmental condition characterized by core social communication deficits and restricted/repetitive behaviors. The majority of cases present with certain medical and psychiatric comorbidities. These include epilepsy, gastrointestinal disorders, attention-deficit/hyperactivity disorder, anxiety, and metabolic dysregulation. While animal models are indispensable in pre-clinical research and studying ASD’s pathobiology, there remains a need to address these comorbidities while modelling major ASD clinical domains. The paper describes a spectrum of animal models for ASD and its comorbid disorders, with a focus on ASD & epilepsy co-occurrence.

Keywords

autism spectrum disorder / social deficits / comorbid conditions / animal model / gene mutations / brain

Cite this article

Download citation ▾
Inna S. Midzyanovskaya. Integrating epilepsy and other comorbidities into autism spectrum disorder research: a call for animal models. Exploration of Neuroscience, 2026, 5 (1) : 1006145 DOI:10.37349/en.2026.1006145

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Sher DA, Gibson JL. Pioneering, prodigious and perspicacious: Grunya Efimovna Sukhareva’s life and contribution to conceptualising autism and schizophrenia. Eur Child Adolesc Psychiatry. 2021; 32:475-90.

[2]

Manouilenko I, Bejerot S. Sukhareva—Prior to Asperger and Kanner. Nord J Psychiatry. 2015; 69:479-82.

[3]

Mason D, Grahame V, Rodgers J. Defining Autism Spectrum Disorder: Building on Kanner (1943): Kanner, L. (1943) Autistic disturbances of affective contact, Nervous Child, 2 (3): 217–50. Clinical Psychology: Revisiting the Classic Studies. 2019; 61–78

[4]

Mnukhin SS, Zelenetskaia AE, Isaev DN. On the syndrome of “early childhood autism” or the Kanner syndrome in children. Zh Nevropatol Psikhiatr Im S S Korsakova. 1967; 67:1501-6.

[5]

Mnukhin SS, Isaev DN. On the organic nature of some forms of schizoid or autistic psychopathy. J Autism Child Schizophr. 1975; 5:99-108.

[6]

Folstein S, Rutter M. INFANTILE AUTISM: A GENETIC STUDY OF 21 TWIN PAIRS. J Child Psychol Psychiatry. 2006; 18:297-321.

[7]

A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium. Hum Mol Genet. 1998; 7:571-8.

[8]

Geschwind DH, State MW. Gene hunting in autism spectrum disorder: on the path to precision medicine. Lancet Neurol. 2015; 14:1109-20.

[9]

Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S, An JY, et al.;Autism Sequencing Consortium;iPSYCH-Broad ConsortiumBetancur C, Cook EH, Gallagher L, Gill M, Sutcliffe JS, Thurm A, et al.Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020; 180:568-84.e23.

[10]

Gallin Z, Kolevzon AM, Reichenberg A, Hankerson SH, Kolevzon A. Racial Differences in the Prevalence of Autism Spectrum Disorder: A Systematic Review. J Autism Dev Disord. 2024; 55:3364-77.

[11]

Argyropoulos A, Gilby KL, Hill-Yardin EL. Studying Autism in Rodent Models: Reconciling Endophenotypes with Comorbidities. Front Hum Neurosci. 2013; 7:417.

[12]

Al-Jawahiri R, Milne E. Resources available for autism research in the big data era: a systematic review. PeerJ. 2017; 5:e2880.

[13]

SPARK Consortium.SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research. Neuron. 2018; 97:488-93.

[14]

Fombonne E, Coppola L, Mastel S, O'Roak BJ. Validation of Autism Diagnosis and Clinical Data in the SPARK Cohort. J Autism Dev Disord. 2021; 52:3383-98.

[15]

Litman A, Sauerwald N, Green Snyder L, Foss-Feig J, Park CY, Hao Y, et al.Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs. Nat Genet. 2025; 57:1611-9.

[16]

Horvath K, Perman JA. Autistic disorder and gastrointestinal disease. Curr Opin Pediatr. 2002; 14:583-7.

[17]

Hsiao EY. Gastrointestinal Issues in Autism Spectrum Disorder. Harv Rev Psychiatry. 2014; 22:104-11.

[18]

Robinson-Agramonte MDLA, Noris García E, Fraga Guerra J, Vega Hurtado Y, Antonucci N, Semprún-Hernández N, et al.Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?. Int J Mol Sci. 2022; 23:3033.

[19]

Noriega DB, Savelkoul HFJ. Immune dysregulation in autism spectrum disorder. Eur J Pediatr. 2013; 173:33-43.

[20]

Rossignol DA, Frye RE. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol. 2014; 5:150.

[21]

Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder. Mol Diagn Ther. 2018; 22:571-93.

[22]

Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Molecular Psychiatry. 2011; 17:290-314.

[23]

Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology. 2006; 13:171-81.

[24]

Bjørklund G, Meguid NA, El-Bana MA, Tinkov AA, Saad K, Dadar M, et al.Oxidative Stress in Autism Spectrum Disorder. Mol Neurobiol. 2020; 57:2314-32.

[25]

Vogel Ciernia A, LaSalle J. The landscape of DNA methylation amid a perfect storm of autism aetiologies. Nat Rev Neurosci. 2016; 17:411-23.

[26]

Deth R, Muratore C, Benzecry J, Power-Charnitsky V, Waly M. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. NeuroToxicology. 2008; 29:190-201.

[27]

Herrera ML, Paraíso-Luna J, Bustos-Martínez I, Barco Á. Targeting epigenetic dysregulation in autism spectrum disorders. Trends Mol Med. 2024; 30:1028-46.

[28]

Rim SJ, Kwak K, Park S. Risk of psychiatric comorbidity with autism spectrum disorder and its association with diagnosis timing using a nationally representative cohort. Res Autism Spectr Disord. 2023; 104:102134.

[29]

Miot S, Akbaraly T, Michelon C, Couderc S, Crepiat S, Loubersac J, et al.Comorbidity Burden in Adults With Autism Spectrum Disorders and Intellectual Disabilities—A Report From the EFAAR (Frailty Assessment in Ageing Adults With Autism Spectrum and Intellectual Disabilities) Study. Front Psychiatry. 2019; 10:617.

[30]

Miot S, Chancel R, Peries M, Crepiat S, Couderc S, Pernon E, et al.Multimorbidity patterns and subgroups among autistic adults with intellectual disability: Results from the EFAAR study. Autism. 2023; 27:762-77.

[31]

Nijhof D, Sosenko F, Ward LM, Cairns D, Hughes L, Rydzewska E. Making a Case for an Autism-Specific Multimorbidity Index: A Comparative Cohort Study. J Autism Dev Disord. 2025

[32]

Kern JK, Trivedi MH, Garver CR, Grannemann BD, Andrews AA, Savla JS, et al.The pattern of sensory processing abnormalities in autism. Autism. 2006; 10:480-94.

[33]

Marco EJ, Hinkley LB, Hill SS, Nagarajan SS. Sensory Processing in Autism: A Review of Neurophysiologic Findings. Pediatr Res. 2011; 69:48R-54R.

[34]

Nakamura T, Dobashi R, Noda H, Ikeda K, Nagayama H, Sasada S. Sensory subtypes of children on the autism spectrum in Japan: Characteristics of participation and family functioning. Autism. 2025; 29:3032-46.

[35]

Huang Y, Nobel Norrman H, Oliva M, van Leeuwen TM, Fransson P, Bölte S, et al.Local and Global Visual Processing in Autism: A Systematic Review and Meta-Analysis of Neuroimaging Studies. J Autism Dev Disord. 2025

[36]

Zheng S, Chen C. Auditory processing deficits in autism spectrum disorder: mechanisms, animal models, and therapeutic directions. J Neural Transm. 2025; 132:781-91.

[37]

Poulsen R, Williams Z, Dwyer P, Pellicano E, Sowman PF, McAlpine D. How auditory processing influences the autistic profile: A review. Autism Res. 2024; 17:2452-70.

[38]

Casterman N, Rossignol M, Colomar A, Cassioli F. Thermoception in Autism Spectrum Disorder: A Concise Systematic Review. Rev J Autism Dev Disord. 2024; 13:556-64.

[39]

Shamay-Tsoory S. Neuroscience of social touch: Emerging directions and challenges. Soc Neurosci. 2024; 19:229-30.

[40]

DuBois D, Ameis SH, Lai MC, Casanova MF, Desarkar P. Interoception in Autism Spectrum Disorder: A review. Int J Dev Neurosci. 2016; 52:104-11.

[41]

Garfinkel SN, Tiley C, O'Keeffe S, Harrison NA, Seth AK, Critchley HD. Discrepancies between dimensions of interoception in autism: Implications for emotion and anxiety. Biol Psychol. 2016; 114:117-26.

[42]

Hatfield TR, Brown RF, Giummarra MJ, Lenggenhager B. Autism spectrum disorder and interoception: Abnormalities in global integration?. Autism. 2017; 23:212-22.

[43]

Ko C, Kim N, Kim E, Song DH, Cheon KA. The effect of epilepsy on autistic symptom severity assessed by the social responsiveness scale in children with autism spectrum disorder. Behav Brain Funct. 2016; 12:20.

[44]

Hirota T, Veenstra-VanderWeele J, Hollander E, Kishi T. Antiepileptic Medications in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. J Autism Dev Disord. 2013; 44:948-57.

[45]

Limbu B, Deb S, Roy M, Lee R, Roy A, Taiwo O. Randomised controlled trials of mood stabilisers for people with autism spectrum disorder: systematic review and meta-analysis. BJPsych Open. 2022; 8:e52.

[46]

Frye RE, Rossignol D, Casanova MF, Brown GL, Martin V, Edelson S, et al.A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel. Front Public Health. 2013; 1:31.

[47]

Ballaban-Gil K, Tuchman R. Epilepsy and epileptiform EEG: Association with autism and language disorders. Ment Retard Dev Disabil Res Rev. 2000; 6:300-8.

[48]

Suurmeijer TP, Reuvekamp MF, Aldenkamp BP. Social Functioning, Psychological Functioning, and Quality of Life in Epilepsy. Epilepsia. 2002; 42:1160-8.

[49]

Noebels JL, Avoli M, Rogawski MA. editors.Jasper and the Basic Mechanisms of the Epilepsies4th edBethesda: National Center for Biotechnology Information (US); 2012

[50]

Penfield W, Jasper H. EPILEPSY AND THE FUNCTIONAL ANATOMY OF THE HUMAN BRAIN. South Med J. 1954; 47:704.

[51]

Gulyaeva NV. Metabolic Neurophilosophy: Linking Brain Function with Body Metabolism. Biochemistry (Moscow). 2026; 91:623-36.

[52]

Milstein JL, Ferris HA. The brain as an insulin-sensitive metabolic organ. Mol Metab. 2021; 52:101234.

[53]

Spinelli M, Fusco S, Grassi C. Brain insulin resistance impairs hippocampal plasticity. Vitam Horm. 2020; 114:281-306.

[54]

Gulyaeva NV. Glucocorticoid Regulation of the Glutamatergic Synapse: Mechanisms of Stress-Dependent Neuroplasticity. J Evol Biochem Physiol. 2021; 57:564-76.

[55]

Gulyaeva NV. Glucocorticoids Orchestrate Adult Hippocampal Plasticity: Growth Points and Translational Aspects. Biochemistry (Moscow). 2023; 88:565-89.

[56]

Peregud DI, Gulyaeva NV. BDNF as a Mediator between Body Metabolism and Brain Function in Health and Disease: The Case of Alcohol Dependence. Biochemistry (Moscow). 2026; 91:713-32.

[57]

Alsalloum M, Tsybko A, Naumenko V. Integrating Dopamine and BDNF Hypotheses: The Role of Dopamine–BDNF Crosstalk in Neuropathologies. Biochemistry (Moscow). 2026; 91:637-57.

[58]

Li J, Mao Y, Zhang H, Xu X. The associations between epilepsy, metabolism, and their clinical implications. Front Endocrinol. 2026; 17:1694550.

[59]

Yudkoff M, Daikhin Y, Melø TM, Nissim I, Sonnewald U, Nissim I. The Ketogenic Diet and Brain Metabolism of Amino Acids: Relationship to the Anticonvulsant Effect. Annu Rev Nutr. 2007; 27:415-30.

[60]

Gubert C, Kong G, Renoir T, Hannan AJ. Exercise, diet and stress as modulators of gut microbiota: Implications for neurodegenerative diseases. Neurobiol Dis. 2020; 134:104621.

[61]

Yan X, Shi L, Zhu X, Zhao Y, Luo J, Li Q, et al.From Microbial Homeostasis to Systemic Pathogenesis: A Narrative Review on Gut Flora’s Role in Neuropsychiatric, Metabolic, and Cancer Disorders. J Inflamm Res. 2025; 18:8851-73.

[62]

Bicknell B, Liebert A, Borody T, Herkes G, McLachlan C, Kiat H. Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome. Int J Mol Sci. 2023; 24:9577.

[63]

Tan J, Taitz J, Nanan R, Grau G, Macia L. Dysbiotic Gut Microbiota-Derived Metabolites and Their Role in Non-Communicable Diseases. Int J Mol Sci. 2023; 24:15256.

[64]

Hours C, Recasens C, Baleyte J. ASD and ADHD Comorbidity: What Are We Talking About?. Front Psychiatry. 2022; 13:837424.

[65]

Rodríguez-Quiroga A, Álvarez Astorga A, Matas Ochoa AM, Quintero J. Understanding the Overlap: Exploring the Complex Comorbidity of ASD and ADHD. European Psychiatry. 2025; 68:S572-3.

[66]

Rong Y, Yang C, Jin Y, Wang Y. Prevalence of attention-deficit/hyperactivity disorder in individuals with autism spectrum disorder: A meta-analysis. Res Autism Spectr Disord. 2021; 83:101759.

[67]

Petruzzelli MG, Matera E, Margari L, Marzulli L, Gabellone A, Cotugno C, et al.An update on the comorbidity of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) and its clinical management. Expert Rev Neurother. 2025; 26:75-89.

[68]

Al Ghamdi K, AlMusailhi J. Attention-deficit Hyperactivity Disorder and Autism Spectrum Disorder: Towards Better Diagnosis and Management. Med Arch. 2024; 78:159-63.

[69]

Bogdańska-Chomczyk E, Majewski MK, Kozłowska A. ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives. Int J Mol Sci. 2025; 26:11020.

[70]

Longo B, Andriolo IRL, de Melo DM, de Souza MM, Prediger RD, da Silva LM. Gastrointestinal Manifestations in Autism Spectrum and Attention-Deficit/Hyperactivity Disorders: Pathogenesis and Drug Targets. Curr Dev Disord Rep. 2025; 12:e12.

[71]

Korteniemi J, Karlsson L, Aatsinki A. Systematic review: Autism spectrum disorder and the gut microbiota. Acta Psychiatr Scand. 2023; 148:242-54.

[72]

Caputi V, Hill L, Figueiredo M, Popov J, Hartung E, Margolis KG, et al.Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies. Front Neurosci. 2024; 18:1341656.

[73]

Gonçalves CL, Doifode T, Rezende VL, Costa MA, Rhoads JM, Soutullo CA. The many faces of microbiota-gut-brain axis in autism spectrum disorder. Life Sci. 2024; 337:122357.

[74]

De Sales-Millán A, Aguirre-Garrido JF, González-Cervantes RM, Velázquez-Aragón JA. Microbiome–Gut–Mucosal–Immune–Brain Axis and Autism Spectrum Disorder (ASD): A Novel Proposal of the Role of the Gut Microbiome in ASD Aetiology. Behav Sci. 2023; 13:548.

[75]

Hung LY, Margolis KG. Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance. Nat Rev Gastroenterol Hepatol. 2023; 21:142-63.

[76]

Mathew NE, McCaffrey D, Walker AK, Mallitt KA, Masi A, Morris MJ, et al.The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers. Mol Autism. 2024; 15:4.

[77]

Yu R, Hafeez R, Ibrahim M, Alonazi WB, Li B. The complex interplay between autism spectrum disorder and gut microbiota in children: A comprehensive review. Behav Brain Res. 2024; 473:115177.

[78]

Galli J, Loi E, Visconti LM, Mattei P, Eusebi A, Calza S, et al.Sleep Disturbances in Children Affected by Autism Spectrum Disorder. Front Psychiatry. 2022; 13:736696.

[79]

Estes A, Hillman A, Chen ML. Sleep and Autism: Current Research, Clinical Assessment, and Treatment Strategies. Focus. 2024; 22:162-9.

[80]

Cohen S, Conduit R, Lockley SW, Rajaratnam SM, Cornish KM. The relationship between sleep and behavior in autism spectrum disorder (ASD): a review. J Neurodev Disord. 2014; 6:44.

[81]

Karavasilis G, Statiri A. Relationship between sleep and measures of attention, executive functions, and processing speed in children with autism spectrum disorder: systematic review. Psychiatriki. 2022; 34:52-65.

[82]

Lane SJ, Leão MA, Spielmann V. Sleep, Sensory Integration/Processing, and Autism: A Scoping Review. Front Psychol. 2022; 13:877527.

[83]

Zaffanello M, Piacentini G, Nosetti L, Zoccante L. Sleep Disordered Breathing in Children with Autism Spectrum Disorder: An In-Depth Review of Correlations and Complexities. Children. 2023; 10:1609.

[84]

Belenguer LM, Cabrera TDLC, Arboledas GP. Sleep Characteristics in Children and Adolescents With Autism Spectrum Disorder. J Sleep Med. 2025; 22:49-62.

[85]

Bernardet M, Crusio WE. Fmr1KO Mice as a Possible Model of Autistic Features. Sci World J. 2006; 6:1164-76.

[86]

Kat R, Arroyo-Araujo M, de Vries RBM, Koopmans MA, de Boer SF, Kas MJH. Translational validity and methodological underreporting in animal research: A systematic review and meta-analysis of the Fragile X syndrome (Fmr1 KO) rodent model. Neurosci Biobehav Rev. 2022; 139:104722.

[87]

Willemsen R, Kooy RF. Mouse models of fragile X-related disorders. Dis Models Mech. 2023; 16:e16.

[88]

Kim KC, Choi CS, Kim JW, Han SH, Cheong JH, Ryu JH, et al.MeCP2 Modulates Sex Differences in the Postsynaptic Development of the Valproate Animal Model of Autism. Mol Neurobiol. 2014; 53:40-56.

[89]

Lombardi LM, Baker SA, Zoghbi HY. MECP2 disorders: from the clinic to mice and back. J Clin Investig. 2015; 125:2914-23.

[90]

Liu Y, Whitfield TW, Bell GW, Guo R, Flamier A, Young RA, et al.Exploring the complexity of MECP2 function in Rett syndrome. Nat Rev Neurosci. 2025; 26:379-98.

[91]

Wu Y, Zhong W, Cui N, Johnson CM, Xing H, Zhang S, et al.Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats. J Neurodev Disord. 2016; 8:23.

[92]

Moretti P, Zoghbi HY. MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev. 2006; 16:276-81.

[93]

Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, et al.Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature. 2010; 468:263-9.

[94]

Uchigashima M, Cheung A, Futai K. Neuroligin-3: A Circuit-Specific Synapse Organizer That Shapes Normal Function and Autism Spectrum Disorder-Associated Dysfunction. Front Mol Neurosci. 2021; 14:749164.

[95]

Wang L, Mirabella VR, Dai R, Su X, Xu R, Jadali A, et al.Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism. Molecular Psychiatry. 2022; 29:1620-35.

[96]

Lai ESK, Nakayama H, Miyazaki T, Nakazawa T, Tabuchi K, Hashimoto K, et al.An Autism-Associated Neuroligin-3 Mutation Affects Developmental Synapse Elimination in the Cerebellum. Front Neural Circuits. 2021; 15:676891.

[97]

Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, et al.Contribution of SHANK3 Mutations to Autism Spectrum Disorder. Am J Hum Genet. 2007; 81:1289-97.

[98]

Peça J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, et al.Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature. 2011; 472:437-42.

[99]

Jiang YH, Ehlers MD. Modeling Autism by SHANK Gene Mutations in Mice. Neuron. 2013; 78:8-27.

[100]

Uchino S, Waga C. SHANK3 as an autism spectrum disorder-associated gene. Brain Dev. 2013; 35:106-10.

[101]

Delling JP, Boeckers TM. Comparison of SHANK3 deficiency in animal models: phenotypes, treatment strategies, and translational implications. J Neurodev Disord. 2021; 13:55.

[102]

Qin L, Ma K, Wang ZJ, Hu Z, Matas E, Wei J, et al.Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition. Nat Neurosci. 2018; 21:564-75.

[103]

Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, et al.Absence of CNTNAP2 Leads to Epilepsy, Neuronal Migration Abnormalities, and Core Autism-Related Deficits. Cell. 2011; 147:235-46.

[104]

Dalla Vecchia E, Mortimer N, Palladino VS, Kittel-Schneider S, Lesch KP, Reif A, et al.Cross-species models of attention-deficit/hyperactivity disorder and autism spectrum disorder. Psychiatr Genet. 2019; 29:1-17.

[105]

Gandhi T, Canepa CR, Adeyelu TT, Adeniyi PA, Lee CC. Neuroanatomical Alterations in the CNTNAP2 Mouse Model of Autism Spectrum Disorder. Brain Sci. 2023; 13:891.

[106]

Gilby KL. A new rat model for vulnerability to epilepsy and autism spectrum disorders. Epilepsia. 2008; 49:108-10.

[107]

Gilby KL, O'Brien TJ. Epilepsy, autism, and neurodevelopment: Kindling a shared vulnerability?. Epilepsy Behav. 2013; 26:370-4.

[108]

Sharma P, Dedeurwaerdere S, Vandenberg MA, Fang K, Johnston LA, Shultz SR, et al.Neuroanatomical differences in FAST and SLOW rat strains with differential vulnerability to kindling and behavioral comorbidities. Epilepsy Behav. 2016; 65:42-8.

[109]

Hernan AE, Alexander A, Jenks KR, Barry J, Lenck-Santini PP, Isaeva E, et al.Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits. Neurobiol Dis. 2014; 63:25-34.

[110]

Khalife MR, Scott RC, Hernan AE. Mechanisms for Cognitive Impairment in Epilepsy: Moving Beyond Seizures. Front Neurol. 2022; 13:878991.

[111]

Vinogradova LV. Audiogenic kindling and secondary subcortico-cortical epileptogenesis: Behavioral correlates and electrographic features. Epilepsy Behav. 2017; 71:142-53.

[112]

Bertram EH, Cornett J. The ontogeny of seizures in a rat model of limbic epilepsy: evidence for a kindling process in the development of chronic spontaneous seizures. Brain Res. 1993; 625:295-300.

[113]

Lakaye B, Nguyen L. Genetic Animal Models of Idiopathic Generalized Epilepsies: What Can We Learn from Them?. Biomedicines. 2025; 13:1301.

[114]

Vergnes M, Marescaux C, Boehrer A, Depaulis A. Are rats with genetic absence epilepsy behaviorally impaired?. Epilepsy Res. 1991; 9:97-104.

[115]

Sarkisova KY, Midzianovskaia IS, Kulikov MA. Depressive-like behavioral alterations and c-Fos expression in the dopaminergic brain regions in WAG/Rij rats with genetic absence epilepsy. Behav Brain Res. 2003; 144:211-26.

[116]

Marks WN, Zabder NK, Cain SM, Snutch TP, Howland JG. The T-type calcium channel antagonist, Z944, alters social behavior in Genetic Absence Epilepsy Rats from Strasbourg. Behav Brain Res. 2019; 361:54-64.

[117]

Sitnikova E. Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats). Biomedicines. 2024; 12:122.

[118]

Abbasova KR, Kuzhuget SM, Tsyba ET. Behavioural and Electrophysiological Features of WAG/Rij Rats with Different Forms of Genetic Epilepsy. J Evol Biochem Physiol. 2024; 60:2072-85.

[119]

Midzyanovskaya IS, Kuznetsova GD, Vinogradova LV, Shatskova AB, Coenen AM, van Luijtelaar G. Mixed forms of epilepsy in a subpopulation of WAG/Rij rats. Epilepsy Behav. 2004; 5:655-61.

[120]

Henbid MT, Marks WN, Collins MJ, Cain SM, Snutch TP, Howland JG. Sociability impairments in Genetic Absence Epilepsy Rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944. Exp Neurol. 2017; 296:16-22.

[121]

Rebik AA, Riga VD, Smirnov KS, Sysoeva OV, Midzyanovskaya IS. Social Behavioral Deficits in Krushinsky-Molodkina Rats, an Animal Model of Audiogenic Epilepsy. J Pers Med. 2022; 12:2062.

[122]

NIKOLAISVILI M, NANOBASHVILI Z, MITAGVARIA N, CHKADUA G, BILANISHVILI I, NOZADZE E, et al.Effects of inhalation of low doses of radon in the Krushinsky-Molodkina rat strain and study of various behavioral characteristics. EXP CLIN MED GA. 2023

[123]

Rebik AA, Broshevitskaya ND, Riga VD, Aleksandrov PL, Zaichenko MI, Midzyanovskaya IS. Ultrasound Communications Reveal Social Aversion in Rats With Contact Motivation Deficits but not Anhedonia. Alpha Psychiatry. 2025; 26:43990.

[124]

Broshevitskaya ND, Rebik AA, Birioukova LM, Zaichenko MI, Midzyanovskaya IS. Aversion But Not Aggression: Emotional Traits of KM Rats in Sociability Tests. OBM Neurobiol. 2026; 10:326.

[125]

Rebik A, Broshevitskaya N, Kuzhuget S, Aleksandrov P, Abbasova K, Zaichenko M, et al.Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky–Molodkina Rats. Biomedicines. 2023; 11:2566.

[126]

S.M. SM, Tsyba E, Surina N, Fedotova I, Midzyanovskaya I, Abbasova K. Social behavior of rats with different predispositions to audiogenic epilepsy before and after repeated sound stimulation. Vestn Mosk univ Ser 16 Biol. 2026; 31

[127]

Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol. 2002; 1:352-8.

[128]

Rodier PM, Ingram JL, Tisdale B, Nelson S, Romano J. Embryological origin for autism: Developmental anomalies of the cranial nerve motor nuclei. The Journal of Comparative Neurology. 1996; 370:247-61.

[129]

Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH. Fetal valproate syndrome and autism: additional evidence of an association. Dev Med Child Neurol. 2001; 43:202.

[130]

Sharma AR, Batra G, Saini L, Sharma S, Mishra A, Singla R, et al.Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure. CNS Neurol Disord Drug Targets. 2022; 21:399-408.

[131]

Schneider T, Przewłocki R. Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism. Neuropsychopharmacology. 2004; 30:80-9.

[132]

Chomiak T, Turner N, Hu B. What We Have Learned about Autism Spectrum Disorder from Valproic Acid. Pathol Res Int. 2013; 2013:712758.

[133]

Roullet FI, Lai JK, Foster JA. In utero exposure to valproic acid and autism—A current review of clinical and animal studies. Neurotoxicol Teratol. 2013; 36:47-56.

[134]

Nicolini C, Fahnestock M. The valproic acid-induced rodent model of autism. Exp Neurol. 2018; 299:217-27.

[135]

Caires CRS, Bossolani-Martins AL. Which form of environmental enrichment is most effective in rodent models of autism?. Behav Process. 2023; 211:104915.

[136]

Li Y, Lu J, Zhang J, Gui W, Xie W. Molecular insights into enriched environments and behavioral improvements in autism: a systematic review and meta-analysis. Front Psychiatry. 2024; 15:1328240.

[137]

Hernández-Arteaga E, Camacho-Candia JA, Pluma-Romo R, Solís-Meza MI, Villafuerte-Vega MN, Aguilar-Guevara F. Environmental Enrichment as a Possible Adjunct Therapy in Autism Spectrum Disorder: Insights from Animal and Human Studies on the Implications of Glial Cells. Neuroglia. 2025; 6:18.

[138]

Careaga M, Murai T, Bauman MD. Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates. Biol Psychiatry. 2017; 81:391-401.

[139]

Kentner AC, Bilbo SD, Brown AS, Hsiao EY, McAllister AK, Meyer U, et al.Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model. Neuropsychopharmacology. 2018; 44:245-58.

[140]

Lammert CR, Lukens JR. Modeling Autism-Related Disorders in Mice with Maternal Immune Activation (MIA). Methods Mol Biol. 2019; 1960:227-36.

[141]

Zawadzka A, Cieślik M, Adamczyk A. The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment. Int J Mol Sci. 2021; 22:11516.

[142]

Atzori M, Garcia-Oscos F, Mendez JA. Role of IL-6 In The Etiology Of Hyperexcitable Neuropsychiatric Conditions: Experimental Evidence And Therapeutic Implications. Future Med Chem. 2012; 4:2177-92.

[143]

Meltzer A, Van de Water J. The Role of the Immune System in Autism Spectrum Disorder. Neuropsychopharmacology. 2016; 42:284-98.

[144]

McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. Autism-like behavioral phenotypes in BTBR T+ tf/J mice. Genes Brain Behav. 2008; 7:152-63.

[145]

Meyza KZ, Blanchard DC. The BTBR mouse model of idiopathic autism – Current view on mechanisms. Neurosci Biobehav Rev. 2017; 76:99-110.

[146]

Tang B, Zhao J, Zhang C, Qi P, Zheng S, Xu C, et al.Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder. Dev Neurobiol. 2024; 84:251-63.

[147]

Olivito I, Avolio E, Minervini D, Soda T, Rocca C, Angelone T, et al.Ketogenic diet ameliorates autism spectrum disorders-like behaviors via reduced inflammatory factors and microbiota remodeling in BTBR T+ Itpr3tf/J mice. Exp Neurol. 2023; 366:114432.

[148]

Buie T, Campbell DB, Fuchs GJ, Furuta GT, Levy J, VandeWater J, et al.Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report. Pediatrics. 2010; 125:S1-18.

[149]

Holingue C, Newill C, Lee LC, Pasricha PJ, Daniele Fallin M. Gastrointestinal symptoms in autism spectrum disorder: A review of the literature on ascertainment and prevalence. Autism Research. 2017; 11:24-36.

[150]

Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016; 165:1762-75.

[151]

Morozova MV, Borisova MA, Snytnikova OA, Achasova KM, Litvinova EA, Tsentalovich YP, et al.Colitis-associated intestinal microbiota regulates brain glycine and host behavior in mice. Sci Rep. 2022; 12:16345.

[152]

Brown DG, Murphy M, Cadeddu R, Bell R, Weis A, Chiaro T, et al.Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members. Nat Commun. 2024; 15:2769.

[153]

Murray DR, Schaller M. Advances in experimental social psychology. In: Olson JM, Zanna MP. editors.The behavioral immune system: Implications for social cognition, social interaction, and social influence. San Diego: Elsevier Academic Press; 2016pp. 75–129.

[154]

Mazzone L, Dooling SW, Volpe E, Uljarević M, Waters JL, Sabatini A, et al.Precision microbial intervention improves social behavior but not autism severity: A pilot double-blind randomized placebo-controlled trial. Cell Host Microbe. 2024; 32:106-16.e6.

[155]

Zhang-James Y, Yang L, Middleton FA, Yang L, Patak J, Faraone SV. Autism-related behavioral phenotypes in an inbred rat substrain. Behav Brain Res. 2014; 269:103-14.

[156]

Gogolla N, Takesian AE, Feng G, Fagiolini M, Hensch TK. Sensory Integration in Mouse Insular Cortex Reflects GABA Circuit Maturation. Neuron. 2014; 83:894-905.

[157]

Gryksa K, Schmidtner AK, Masís-Calvo M, Rodríguez-Villagra OA, Havasi A, Wirobski G, et al.Selective breeding of rats for high (HAB) and low (LAB) anxiety-related behaviour: A unique model for comorbid depression and social dysfunctions. Neurosci Biobehav Rev. 2023; 152:105292.

[158]

Pascucci T, Colamartino M, Fiori E, Sacco R, Coviello A, Ventura R, et al.P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse. Brain Sci. 2020; 10:233.

[159]

Chelini G, Fortunato-Asquini T, Cerilli E, Monsorno K, Catena B, Dall'O' GM, et al.Early-life adversities compromise behavioral development in male and female mice heterozygous for CNTNAP2. Neurobiology of Stress. 2025; 36:100726.

[160]

Sheibani Tezerji S, Jonaidi H, Sheibani V, Moslemizadeh A, Azizi S, Dalili M, et al.Effects of Valproic Acid and Maternal Deprivation on Autism-Like Behaviours and Neurodevelopmental Outcomes in Female and Male Rats. Int J Dev Neuroscie. 2025; 85:e70004.

PDF (2056KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/