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Cited by 37Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroendocrine regulation and behavior

Tactile stimulation improves neuroanatomical pathology but not behavior in rats prenatally exposed to valproic acid

Raza, S., Harker, A., Richards, S., Kolb, B., Gibb, R.·2015·Behavioural Brain Research
DOI 10.1016/j.bbr.2014.12.055
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Abstract

Autism is a severe neurodevelopmental disorder with a population prevalence of 1 in 68, and dramatically increasing. While no single pharmacologic intervention has successfully targeted the core symptoms of autism, emerging evidence suggests that postnatal environmental manipulations may offer greater therapeutic efficacy. Massage therapy, or tactile stimulation (TS), early in life has repeatedly been shown to be an effective, low-cost, therapeutic approach in ameliorating the cognitive, social, and emotional symptoms of autism. While early TS treatment attenuates many of the behavioral aberrations among children with autism, the neuroanatomical correlates driving such changes are unknown. The present study assessed the therapeutic effects of early TS treatment on behavior and neuroanatomy using the valproic acid (VPA) rodent model of autism. Rats were prenatally exposed to VPA on gestational day 12.5 and received TS shortly following birth. Whereas TS reversed almost all the VPA-induced alterations in neuroanatomy, it failed to do so behaviorally. The TS VPA animals, when compared to VPA animals, did not exhibit altered or improved behavior in the delayed non-match-to-sample T-maze, Whishaw tray reaching, activity box, or elevated plus maze tasks. Anatomically, however, there were significant increases in dendritic branching and spine density in the medial prefrontal cortex, orbital frontal cortex, and amygdala in VPA animals following early TS treatment, suggesting a complete reversal or remediation of the VPA-induced effects in these regions. The results suggest that postnatal TS, during a critical period in development, acts as a powerful reorganization tool that can ameliorate the neuroanatomical consequences of prenatal VPA exposure.

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  • In prenatal VPA models, spine density is reduced in the PFC, orbital PFC, cerebellum, and dorsal hippocampus, but increased in the ventral hippocampus, basolateral amygdala, and nucleus accumbens.

    “Spine density is reduced in the PFC [42, 250, 297], orbital PFC [250, 297], cerebellum [250], and in the dorsal hippocampus [42, 346], but increased in the ventral hippocampus, basolateral amygdala and nucleus accumbens [42].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [297]

  • In prenatal VPA models, reduced dendritic branching but not length in the orbital PFC was reported in one study, whereas another showed decreased dendritic length in the same brain region.

    “Reduced dendritic branching but not length in the orbital PFC was reported in one study [297], whereas another showed decreased dendritic length in the same brain region [250].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [297]

  • In rodent models of prenatal VPA exposure, basal dendrites show no change in length on layer II pyramidal neurons in the motor cortex, decreased length and complexity in the medial PFC and hippocampal CA1, and increased length and complexity in the nucleus accumbens and basolateral amygdala.

    “Basal dendrites in rodent models of prenatal VPA exposure show no change in length on layer II pyramidal neurons in the motor cortex [331], decreased length and complexity in the medial PFC [297] and the hippocampal CA1, and increased length and complexity in the nucleus accumbens and basolateral amygdala [42].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [297]

  • In prenatal VPA models, apical dendrite complexity but not length is increased on layer II pyramidal neurons in the motor cortex, decreased in the medial PFC, or unchanged in layer V pyramidal neurons of the somatosensory cortex.

    “In the case of apical dendrites, complexity, but not length, is increased on layer II pyramidal neurons in the motor cortex [331], decreased in the medial PFC [297], or is unchanged in layer V pyramidal neurons of the somatosensory cortex following VPA exposure in rodents [301].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [297]

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Authors
Raza, S., Harker, A., Richards, S., Kolb, B., & Gibb, R.
Affiliations
University of Lethbridge (CA)
Corresponding author
Raza, S.
ORCID
Venue
Behavioural Brain Research
Publisher
Elsevier BV
Published
2015-04
Volume
282
Pages
25-36
ISSN
0166-4328 (ISSN-L)
DOI
10.1016/j.bbr.2014.12.055
OpenAlex
W2066521976
Cited by
37
References
91
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 6 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 4
FWCI
2.41
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Behavioural Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Natural Sciences and Engineering Research Council of Canada
  • Canadian Institute for Advanced Research
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
tactile stimulation, autism spectrum disorder, valproic acid, prenatal drug exposure, dendritic branching, dendritic spine density, medial prefrontal cortex, orbitofrontal cortex, amygdala, postnatal intervention, behavioral deficits, elevated plus maze
MeSH terms
Amygdala, Animals, Autistic Disorder, Behavior, Animal, Dendrites, Disease Models, Animal, Female, Frontal Lobe, Male, Motor Activity, Neuronal Plasticity, Pregnancy, Prenatal Exposure Delayed Effects, Social Behavior, Touch, Valproic Acid, Prefrontal Cortex, Maze Learning, Rats, Long-Evans, Dendritic Spines, Rats

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