title: Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats.
abstract: Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF) small peptide mimetic, Peptide 6 (P6), which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF) expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism.
authors.affiliation: Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America; Neural and Behavioral Science Graduate Program, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York, United States of America; SUNY Downstate/NYSIBR Center for Developmental Neuroscience (CDN), Staten Island, New York, United States of America.
authors.forename: Syed Faraz
authors.initials: SF
authors.lastname: Kazim
authors.affiliation: Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America.
authors.forename: Maria Del Carmen
authors.initials: Mdel C
authors.lastname: Cardenas-Aguayo
authors.affiliation: Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Arif
authors.affiliation: Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Blanchard
authors.affiliation: Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America.
authors.forename: Fatima
authors.initials: F
authors.lastname: Fayyaz
authors.affiliation: Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America.
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.affiliation: Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America; SUNY Downstate/NYSIBR Center for Developmental Neuroscience (CDN), Staten Island, New York, United States of America.
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D002675:Child, Preschool; D020934:Ciliary Neurotrophic Factor / Q000737:chemistry*; D002658:Developmental Disabilities / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D057786:Peptidomimetics / Q000494:pharmacology* / Q000627:therapeutic use; D010641:Phenotype; D051381:Rats; D012919:Social Behavior; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D018696:Neuroprotective Agents; D057786:Peptidomimetics