Treadmill Exercise Improves Stereotypical Behaviors in Autistic Rats
Abstract
Background: Autism spectrum disorder (ASD) is identified by developmental deficits that lead to repetitive/stereotypic patterns of behavior and impaired social interactions. Studies have been indicated that exercise can decrease stereotypic behaviors in animal models of ASD. This research was designed to discover the effects of different models of forced exercise on stereotypical behaviors in a rat model of ASD induced by thimerosal (THIM). Materials and Methods: Fifty-six male Wistar rats were divided into eight groups. The rats were received saline (1 ml/kg) or THIM (300 μg Hg/kg) by four intramuscular injections on 7, 9, 11, and 15 postnatal days. The rats were also treated by several protocols of treadmill exercise, including non-sedentary, sedentary, protocol 1, protocol 2, and a combination of protocols 1 and 2. Results: Our study showed that THIM decreased the grooming time compared to the control group. Moreover, protocol 2 exercise significantly decreased grooming time in stranger zone 2 compared to the THIM group. Conclusions: Our results showed that stereotypical behaviors exaggerated by THIM and moderate exercise could improve ASD-associated behaviors in the THIM-treated rats. Hence, moderate exercise may be a useful protocol for the treatment of ASD. [GMJ.2022;11:e1990]References
Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013.
Brugha T, Cooper SA, McManus S, Purdon S, Smith J, Scott F, et al. Estimating the prevalence of autism spectrum conditions in adults: extending the 2007 adult psychiatric morbidity survey. The NHS Informaiton Centre. 2012.
Lever AG, Geurts HM. Psychiatric co-occurring symptoms and disorders in young, middle-aged, and older adults with autism spectrum disorder. J Autism Dev Disord. 2016;46(6):1916-30.
https://doi.org/10.1007/s10803-016-2722-8
PMid:26861713 PMCid:PMC4860203
Petschenka G, Agrawal AA. How herbivores coopt plant defenses: natural selection, specialization, and sequestration. Curr Opin Insect Sci. 2016;14:17-24.
https://doi.org/10.1016/j.cois.2015.12.004
PMid:27436642
Geier DA, Kern JK, King PG, Sykes LK, Geier MR. A case-control study evaluating the relationship between Thimerosal-containing Haemophilus influenzae Type b vaccine administration and the risk for a pervasive developmental disorder diagnosis in the United States. Biol Trace Elem Res. 2015;163(1-2):28-38.
https://doi.org/10.1007/s12011-014-0169-3
PMid:25382662 PMCid:PMC4297306
Adamson P, Auty D, Ayres D, Backhouse C, Barr G, Betancourt M, et al. Improved search for muon-neutrino to electron-neutrino oscillations in MINOS. Phys Rev Lett. 2011;107(18):181802.
https://doi.org/10.1103/PhysRevLett.107.181802
PMid:22107623
Gallagher C, Goodman M. Hepatitis B triple series vaccine and developmental disability in US children aged 1-9 years. Toxicological and Environmental Chemistry. 2008;90(5):997-1008.
https://doi.org/10.1080/02772240701806501
Young HA, Geier DA, Geier MR. Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink. J Neurol Sci. 2008;271(1-2):110-8.
https://doi.org/10.1016/j.jns.2008.04.002
PMid:18482737
Bahrami F, Movahedi A, Marandi SM, Abedi A. Kata techniques training consistently decreases stereotypy in children with autism spectrum disorder. Res Dev Disabil. 2012;33(4):1183-93.
https://doi.org/10.1016/j.ridd.2012.01.018
PMid:22502844
Bahrami F, Movahedi A, Marandi SM, Sorensen C. The effect of karate techniques training on communication deficit of children with autism spectrum disorders. J Autism Dev Disord. 2016;46(3):978-86.
https://doi.org/10.1007/s10803-015-2643-y
PMid:26577688
Pan C-Y, Tsai C-L, Hsieh K-W. Physical activity correlates for children with autism spectrum disorders in middle school physical education. Res Q Exerc Sport. 2011;82(3):491-8.
https://doi.org/10.1080/02701367.2011.10599782
PMid:21957708
Iliadis I, Apteslis N. The role of physical education and exercise for children with Autism Spectrum Disorder and the effects on socialization, communication, behavior, fitness, and quality of life. Dialogues in Clinical Neuroscience & Mental Health. 2020;3(1):71-81.
Sorensen C, Zarrett N. Benefits of physical activity for adolescents with autism spectrum disorders: A comprehensive review. Review Journal of Autism and Developmental Disorders. 2014;1(4):344-53.
https://doi.org/10.1007/s40489-014-0027-4
Petrus C, Adamson SR, Block L, Einarson SJ, Sharifnejad M, Harris SR. Effects of exercise interventions on stereotypic behaviours in children with autism spectrum disorder. Physiother Can. 2008;60(2):134-45.
https://doi.org/10.3138/physio.60.2.134
PMid:20145777 PMCid:PMC2792819
Carneiro MFH, Souza JMO, Grotto D, Batista BL, de Oliveira Souza VC, Barbosa Jr F. A systematic study of the disposition and metabolism of mercury species in mice after exposure to low levels of thimerosal (ethylmercury). Environ Res. 2014;134:218-27.
https://doi.org/10.1016/j.envres.2014.07.009
PMid:25173055
Hornig M, Chian D, Lipkin WI. Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry. 2004;9(9):833-45.
https://doi.org/10.1038/sj.mp.4001529
PMid:15184908
Kim D-H, Ko I-G, Kim B-K, Kim T-W, Kim S-E, Shin M-S, et al. Treadmill exercise inhibits traumatic brain injury-induced hippocampal apoptosis. Physiol Behav. 2010;101(5):660-5.
https://doi.org/10.1016/j.physbeh.2010.09.021
PMid:20888848
Zagaar M, Alhaider I, Dao A, Levine A, Alkarawi A, Alzubaidy M, et al. The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence. Neurobiol Dis. 2012;45(3):1153-62.
https://doi.org/10.1016/j.nbd.2011.12.039
PMid:22227452
Ebrahimi-Ghiri M, Shahini F, Khakpai F, Zarrindast MR. Antinociceptive and antidepressive efficacies of the combined ineffective doses of S-ketamine and URB597.Naunyn Schmiedebergs Arch Pharmacol. 2019;392(11):1393-400.
https://doi.org/10.1007/s00210-019-01676-5
PMid:31250026
Gjevik E, Eldevik S, Fjæran-Granum T, Sponheim E. Kiddie-SADS reveals high rates of DSM-IV disorders in children and adolescents with autism spectrum disorders. J Autism Dev Disord. 2011;41(6):761-9.
https://doi.org/10.1007/s10803-010-1095-7
PMid:20824493 PMCid:PMC3094530
Staples KL, Reid G. Fundamental movement skills and autism spectrum disorders. J Autism Dev Disord. 2010;40(2):209-17.
https://doi.org/10.1007/s10803-009-0854-9
PMid:19685284
Dodonova S, Bobyntsev I, Belykh A, Telegina I, Muzaleva YA, Andreeva L, et al. Effects of peptides ACTH6-9 PGP and ACTH4-7-PGP on anxiety levels in rats in punished and unpunished behavior. Neuroscience and Behavioral Physiology. 2020;50(9):1203-8.
https://doi.org/10.1007/s11055-020-01022-w
Olczak M, Duszczyk M, Mierzejewski P, Meyza K, Majewska MD. Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats. Behav Brain Res. 2011;223(1):107-18.
https://doi.org/10.1016/j.bbr.2011.04.026
PMid:21549155
Schmitz SO, McFadden BA, Golem DL, Pellegrino JK, Walker AJ, Sanders DJ, et al. The Effects of Exercise Dose on Stereotypical Behavior in Children with Autism. Med Sci Sports Exerc. 2017;49(5):983-90.
https://doi.org/10.1249/MSS.0000000000001197
PMid:28060033
Gordon R, Handleman JS, Harris SL. The effects of contingent versus non-contingent running on the out-of-seat behavior of an autistic boy. Child & family behavior therapy. 1986;8(3):37-44.
https://doi.org/10.1300/J019v08n03_04
Kern L, Koegel RL, Dunlap G. The influence of vigorous versus mild exercise on autistic stereotyped behaviors. Journal of autism and developmental disorders. 1984;14(1):57-67.
https://doi.org/10.1007/BF02408555
PMid:6706897
Brand S, Jossen S, Holsboer-Trachsler E, Puehse U, Gerber M. Impact of aerobic exercise on sleep and motor skills in children with autism spectrum disorders-a pilot study. Neuropsychiatr Dis Treat. 2015;11:1911.
https://doi.org/10.2147/NDT.S85650
PMid:26346856 PMCid:PMC4531010
Bremer E, Lloyd M. School-based fundamental-motor-skill intervention for children with autism-like characteristics: an exploratory study. Adapt Phys Activ Q. 2016;33(1):66-88.
https://doi.org/10.1123/APAQ.2015-0009
PMid:26785501
Ketcheson L, Hauck J, Ulrich D. The effects of an early motor skill intervention on motor skills, levels of physical activity, and socialization in young children with autism spectrum disorder: A pilot study. Autism. 2017;21(4):481-92.
https://doi.org/10.1177/1362361316650611
PMid:27354429
Lang R, Koegel LK, Ashbaugh K, Regester A, Ence W, Smith W. Physical exercise and individuals with autism spectrum disorders: A systematic review. Research in Autism Spectrum Disorders. 2010;4(4):565-76.
https://doi.org/10.1016/j.rasd.2010.01.006
Levinson LJ, Reid G. The effects of exercise intensity on the stereotypic behaviors of individuals with autism. Adapted Physical Activity Quarterly. 1993;10(3):255-68.
https://doi.org/10.1123/apaq.10.3.255
Celiberti DA, Bobo HE, Kelly KS, Harris SL, Handleman JS. The differential and temporal effects of antecedent exercise on the self-stimulatory behavior of a child with autism. Res Dev Disabil. 1997;18(2):139-50.
https://doi.org/10.1016/S0891-4222(96)00032-7
Elliott RO, Dobbin AR, Rose GD, Soper HV. Vigorous, aerobic exercise versus general motor training activities: Effects on maladaptive and stereotypic behaviors of adults with both autism and mental retardation. J Autism Dev Disord. 1994;24(5):565-76.
https://doi.org/10.1007/BF02172138
PMid:7814306
Schønecker B, Heller KE. The involvement of dopamine (DA) and serotonin (5-HT) in stress-induced stereotypies in bank voles (Clethrionomys glareolus). Appl Anim Behav Sci. 2001;73(4):311-9.
https://doi.org/10.1016/S0168-1591(01)00143-5
Lanovaz MJ. Towards a comprehensive model of stereotypy: Integrating operant and neurobiological interpretations. Res Dev Disabil. 2011;32(2):447-55.
https://doi.org/10.1016/j.ridd.2010.12.026
PMid:21236636
Meeusen R, De Meirleir K. Exercise and brain neurotransmission. Sports Med. 1995;20(3):160-88.
https://doi.org/10.2165/00007256-199520030-00004
PMid:8571000
Lim AL, Taylor DA, Malone DT. Consequences of early life MK-801 administration: long-term behavioural effects and relevance to schizophrenia research. Behav Brain Res. 2012;227(1):276-86.
https://doi.org/10.1016/j.bbr.2011.10.052
PMid:22085878
Mohammadi S, Asadi-Shekaari M, Basiri M, Parvan M, Shabani M, Nozari M. Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of NMDA receptor function. Psychopharmacology (Berl). 2020;237(1):199-208.
https://doi.org/10.1007/s00213-019-05357-2
PMid:31595334
Soderling TR. CaM-kinases: modulators of synaptic plasticity. Curr Opin Neurobiol. 2000;10(3):375-80.
https://doi.org/10.1016/S0959-4388(00)00090-8
Argiolas A, Melis MR, Murgia S, Schiöth HB. ACTH-and α-MSH-induced grooming, stretching, yawning and penile erection in male rats: site of action in the brain and role of melanocortin receptors. Brain Res Bull. 2000;51(5):425-31.
https://doi.org/10.1016/S0361-9230(99)00270-1
Molteni R, Ying Z, Gómez‐Pinilla F. Differential effects of acute and chronic exercise on plasticity‐related genes in the rat hippocampus revealed by microarray. Eur J Neurosci. 2002;16(6):1107-16.
https://doi.org/10.1046/j.1460-9568.2002.02158.x
PMid:12383240

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