title: Tactile stimulation improves neuroanatomical pathology but not behavior in rats prenatally exposed to valproic acid.
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.
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Canada. Electronic address: sarah.raza@uleth.ca.
authors.forename: S
authors.initials: S
authors.lastname: Raza
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Harker
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Richards
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Canada; Canadian Institute for Advanced Research Program in Child Brain Development, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Kolb
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Gibb
mesh_terms: D000679:Amygdala / Q000473:pathology; D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology / Q000628:therapy*; D001522:Behavior, Animal; D003712:Dendrites / Q000473:pathology; D049229:Dendritic Spines / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D008297:Male; D018782:Maze Learning; D009043:Motor Activity; D009473:Neuronal Plasticity; D017397:Prefrontal Cortex / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology / Q000523:psychology; D051381:Rats; D020318:Rats, Long-Evans; D012919:Social Behavior; D014110:Touch; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D014635:Valproic Acid
keywords: Amygdala; Autism; Dendritic morphology; Prefrontal cortex; Tactile stimulation; Valproic acid