PMID- 25769033 OWN - NLM STAT- MEDLINE DCOM- 20160127 LR - 20200306 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats. PG - e0118627 LID - 10.1371/journal.pone.0118627 [doi] LID - e0118627 AB - 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. FAU - Kazim, Syed Faraz AU - Kazim SF AD - 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. FAU - Cardenas-Aguayo, Maria Del Carmen AU - Cardenas-Aguayo Mdel C AD - 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. FAU - Arif, Mohammad AU - Arif M AD - 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. FAU - Blanchard, Julie AU - Blanchard J AD - 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. FAU - Fayyaz, Fatima AU - Fayyaz F AD - 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. FAU - Grundke-Iqbal, Inge AU - Grundke-Iqbal I AD - 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. FAU - Iqbal, Khalid AU - Iqbal K AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150313 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Peptidomimetics) SB - IM MH - Animals MH - Autistic Disorder/*blood/*drug therapy/pathology/physiopathology MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/genetics MH - Cell Death/drug effects MH - Child, Preschool MH - Ciliary Neurotrophic Factor/*chemistry MH - Developmental Disabilities/drug therapy/etiology MH - Female MH - Gene Expression Regulation/drug effects MH - Humans MH - Male MH - Mice MH - Neurons/drug effects/pathology MH - Neuroprotective Agents/*pharmacology/therapeutic use MH - Oxidative Stress/drug effects MH - Peptidomimetics/*pharmacology/therapeutic use MH - Phenotype MH - Rats MH - Social Behavior MH - Vocalization, Animal/drug effects PMC - PMC4359103 COIS- Competing Interests: This study was partly supported by EVER NeuroPharma GmbH, Unterach, Austria. Based on studies described in this manuscript, the authors submitted a patent application to the United States Patent and Trademark Office on 12/11/2014, entitled: "Treatment of Autism Spectrum Disorders with Ciliary Neurotrophic Factor Peptide Mimetic"; application number US62/083,570; Inventors: Khalid Iqbal and Inge Grundke-Iqbal. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. EDAT- 2015/03/15 06:00 MHDA- 2016/01/28 06:00 PMCR- 2015/03/13 CRDT- 2015/03/14 06:00 PHST- 2014/11/05 00:00 [received] PHST- 2015/01/21 00:00 [accepted] PHST- 2015/03/14 06:00 [entrez] PHST- 2015/03/15 06:00 [pubmed] PHST- 2016/01/28 06:00 [medline] PHST- 2015/03/13 00:00 [pmc-release] AID - PONE-D-14-49217 [pii] AID - 10.1371/journal.pone.0118627 [doi] PST - epublish SO - PLoS One. 2015 Mar 13;10(3):e0118627. doi: 10.1371/journal.pone.0118627. eCollection 2015.