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Abstract
Neonatal isolation is a widely accepted model to study the long-term behavioral changes produced by the early life events. However, it remains unknown whether neonatal isolation can induce autistic-like behaviors, and if so, whether pharmacological treatment can overcome it. Here, we reported that newborn rats subjected to individual isolations from their mother and nest for 1 h per day from postnatal days 1–9 displayed apparent autistic-like symptoms including social deficits, excessive repetitive self-grooming behavior, and increased anxiety- and depressive-like behaviors tested in young adult (postnatal days 42–56) compared to normal reared controls. Furthermore, these behavioral changes were accompanied by impaired adult hippocampal neurogenesis and reduced the ratio of excitatory/inhibitory synaptic transmissions, as reflected by an increase in spontaneous inhibitory postsynaptic current (sIPSC) and normal spontaneous excitatory postsynaptic current (sEPSC) in the hippocampal CA1 pyramidal neuron. More importantly, chronic administration of lithium, a clinically used mood stabilizer, completely overcame neonatal isolation-induced autistic-like behaviors, and restored adult hippocampal neurogenesis as well as the balance between excitatory and inhibitory activities to physiological levels. These findings indicate that neonatal isolation may produce autistic-like behaviors, and lithium may be a potential therapeutic agent against autism spectrum disorders (ASD) during development.
Highlights
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder (Mulvihill et al, 2009), which is characterized by impaired social interactions and enhanced repetitive or stereotyped behavior, as well as marked inflexibility to environmental contingency changes (American Psychiatric Association, 1994; Arndt et al, 2005; DiCicco-Bloom et al, 2006)
To determine whether neonatal isolation can produce autistic-like behaviors, we firstly tested social interaction, a core symptom of autism, in young adult rats that were subjected to maternal separation during postnatal days 1–9 (PND 1–9)
These results indicate that neonatal isolation produces autistic-like social deficits, and chronic lithium administration can overcome it
Summary
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder (Mulvihill et al, 2009), which is characterized by impaired social interactions and enhanced repetitive or stereotyped behavior, as well as marked inflexibility to environmental contingency changes (American Psychiatric Association, 1994; Arndt et al, 2005; DiCicco-Bloom et al, 2006). The cause of autism appears to be primarily genetic, with an estimated heritability of over 90% obtained from epidemiological studies of autistic twins (Bailey et al, 1995). Most previous studies have focused on the role of congenital genetic factors in autism (Abrahams and Geschwind, 2008; State and Levitt, 2011; Devlin and Scherer, 2012). Correlations between acquired factors and autism occurrence have not been extensively investigated, there is a growing body of evidence to show that valproic acid exposure, around the critical time period of neural tube closure, leads to autistic-like anatomical and behavioral phenotypes in the offspring in human and in animal models (Christianson et al, 1994; Schneider and Przewlocki, 2005; Christensen et al, 2013)
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