PMID- 26586008 OWN - NLM STAT- MEDLINE DCOM- 20170110 LR - 20181113 IS - 1573-7365 (Electronic) IS - 0885-7490 (Linking) VI - 31 IP - 2 DP - 2016 Apr TI - Intracerebroventricular administration of alpha-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats. PG - 377-83 LID - 10.1007/s11011-015-9768-8 [doi] AB - Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-chain alpha-ketoacids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. However, the effect of accumulating alpha-ketoacids in MSUD on neurotrophic factors has not been investigated. Thus, the objective of the present study was to evaluate the effects of acute intracerebroventricular administration of alpha-ketoisocaproic acid (KIC) on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brains of young male rats. Ours results showed that intracerebroventricular administration of KIC decreased BDNF levels in hippocampus, striatum and cerebral cortex, without induce a detectable change in pro-BDNF levels. Moreover, NGF levels in the hippocampus were reduced after intracerebroventricular administration of KIC. In conclusion, these data suggest that the effects of KIC on demyelination and memory processes may be mediated by reduced trophic support of BDNF and NGF. Moreover, lower levels of BDNF and NGF are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying the psychopathology of MSUD, supporting the hypothesis of a neurodegenerative process in MSUD. FAU - Wisniewski, Miriam S W AU - Wisniewski MS AD - Laboratorio de Bioenergetica e Nucleo de Excelencia em Neurociencias Aplicadas de Santa Catarina (NENASC), Programa de Pos-Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, Av. Universitaria, 1105, Criciuma, SC, 88806-000, Brazil. AD - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, RS, Brazil. FAU - Carvalho-Silva, Milena AU - Carvalho-Silva M AD - Laboratorio de Bioenergetica e Nucleo de Excelencia em Neurociencias Aplicadas de Santa Catarina (NENASC), Programa de Pos-Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, Av. Universitaria, 1105, Criciuma, SC, 88806-000, Brazil. AD - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, RS, Brazil. FAU - Gomes, Lara M AU - Gomes LM AD - Laboratorio de Bioenergetica e Nucleo de Excelencia em Neurociencias Aplicadas de Santa Catarina (NENASC), Programa de Pos-Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, Av. Universitaria, 1105, Criciuma, SC, 88806-000, Brazil. AD - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, RS, Brazil. FAU - Zapelini, Hugo G AU - Zapelini HG AD - Laboratorio de Erros Inatos do Metabolismo, Programa de Pos-Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, Criciuma, SC, Brazil. FAU - Schuck, Patricia F AU - Schuck PF AD - Laboratorio de Erros Inatos do Metabolismo, Programa de Pos-Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, Criciuma, SC, Brazil. FAU - Ferreira, Gustavo C AU - Ferreira GC AD - Laboratorio de Neuroquimica, Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Scaini, Giselli AU - Scaini G AD - Laboratorio de Bioenergetica e Nucleo de Excelencia em Neurociencias Aplicadas de Santa Catarina (NENASC), Programa de Pos-Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, Av. Universitaria, 1105, Criciuma, SC, 88806-000, Brazil. AD - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, RS, Brazil. FAU - Streck, Emilio L AU - Streck EL AD - Laboratorio de Bioenergetica e Nucleo de Excelencia em Neurociencias Aplicadas de Santa Catarina (NENASC), Programa de Pos-Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, Av. Universitaria, 1105, Criciuma, SC, 88806-000, Brazil. emiliostreck@gmail.com. AD - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, RS, Brazil. emiliostreck@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151120 PL - United States TA - Metab Brain Dis JT - Metabolic brain disease JID - 8610370 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Keto Acids) RN - 0 (Protein Precursors) RN - 0 (brain-derived neurotrophic factor precursor) RN - 816-66-0 (alpha-ketoisocaproic acid) SB - IM MH - Age Factors MH - Animals MH - Brain/*drug effects/metabolism MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Keto Acids/administration & dosage/*pharmacology MH - Male MH - Oxidative Stress/drug effects MH - Protein Precursors/*metabolism MH - Rats, Wistar OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Maple syrup urine disease OT - Nerve growth factor OT - alpha-ketoisocaproic acid EDAT- 2015/11/21 06:00 MHDA- 2017/01/11 06:00 CRDT- 2015/11/21 06:00 PHST- 2015/08/28 00:00 [received] PHST- 2015/11/13 00:00 [accepted] PHST- 2015/11/21 06:00 [entrez] PHST- 2015/11/21 06:00 [pubmed] PHST- 2017/01/11 06:00 [medline] AID - 10.1007/s11011-015-9768-8 [pii] AID - 10.1007/s11011-015-9768-8 [doi] PST - ppublish SO - Metab Brain Dis. 2016 Apr;31(2):377-83. doi: 10.1007/s11011-015-9768-8. Epub 2015 Nov 20.