PMID- 22437340 OWN - NLM STAT- MEDLINE DCOM- 20120507 LR - 20220408 IS - 1554-6578 (Electronic) IS - 0022-3069 (Print) IS - 0022-3069 (Linking) VI - 71 IP - 4 DP - 2012 Apr TI - Altered balance of proteolytic isoforms of pro-brain-derived neurotrophic factor in autism. PG - 289-97 LID - 10.1097/NEN.0b013e31824b27e4 [doi] AB - Defects in synaptic development and plasticity may lead to autism. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptogenesis and synaptic plasticity. BDNF is synthesized as a precursor, pro-BDNF, which can be processed into either a truncated form or into mature BDNF. Previous studies reported increased BDNF-immunoreactive protein in autism, but the mechanism of this increase has not been investigated. We examined BDNF mRNA by real-time reverse transcription-polymerase chain reaction and BDNF protein by Western blotting and enzyme-linked immunosorbent assay in postmortem fusiform gyrus tissue from 11 patients with autism and 14 controls. BDNF mRNA levels were not different in the autism versus control samples, but total BDNF-like immunoreactive protein, measured by enzyme-linked immunosorbent assay, was greater in autism than in controls. Western blotting revealed greater pro-BDNF and less truncated BDNF in autism compared with controls. These data demonstrate that increased levels of BDNF-immunoreactive protein in autism are not transcriptionally driven. Increased pro-BDNF and reduced truncated BDNF are consistent with defective processing of pro-BDNF to its truncated form. Distortion of the balance among the 3 BDNF isoforms, each of which may exhibit different biological activities, could lead to changes in connectivity and synaptic plasticity and, hence, behavior. Thus, imbalance in proteolytic isoforms is a possible new mechanism for altered synaptic plasticity leading to autism. FAU - Garcia, Kristine L P AU - Garcia KL AD - Departments of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada. FAU - Yu, Guanhua AU - Yu G FAU - Nicolini, Chiara AU - Nicolini C FAU - Michalski, Bernadeta AU - Michalski B FAU - Garzon, Diego J AU - Garzon DJ FAU - Chiu, Victor S AU - Chiu VS FAU - Tongiorgi, Enrico AU - Tongiorgi E FAU - Szatmari, Peter AU - Szatmari P FAU - Fahnestock, Margaret AU - Fahnestock M LA - eng GR - 85042/Canadian Institutes of Health Research/Canada PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neuropathol Exp Neurol JT - Journal of neuropathology and experimental neurology JID - 2985192R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Isoforms) RN - 0 (Protein Precursors) RN - 0 (RNA, Messenger) RN - 0 (brain-derived neurotrophic factor precursor) SB - IM MH - Adult MH - Autistic Disorder/diagnosis/genetics/*metabolism MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Child MH - Child, Preschool MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neuronal Plasticity/genetics MH - Protein Isoforms/genetics/metabolism MH - Protein Precursors/genetics/*metabolism MH - Proteolysis MH - RNA, Messenger/metabolism MH - Synapses/genetics MH - Young Adult PMC - PMC3419254 MID - CAMS2282 OID - NLM: CAMS2282 EDAT- 2012/03/23 06:00 MHDA- 2012/05/09 06:00 PMCR- 2013/04/01 CRDT- 2012/03/23 06:00 PHST- 2012/03/23 06:00 [entrez] PHST- 2012/03/23 06:00 [pubmed] PHST- 2012/05/09 06:00 [medline] PHST- 2013/04/01 00:00 [pmc-release] AID - 00005072-201204000-00004 [pii] AID - 10.1097/NEN.0b013e31824b27e4 [doi] PST - ppublish SO - J Neuropathol Exp Neurol. 2012 Apr;71(4):289-97. doi: 10.1097/NEN.0b013e31824b27e4.