PMID- 23700454 OWN - NLM STAT- MEDLINE DCOM- 20131224 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 5 DP - 2013 TI - Systemic delivery of recombinant brain derived neurotrophic factor (BDNF) in the R6/2 mouse model of Huntington's disease. PG - e64037 LID - 10.1371/journal.pone.0064037 [doi] LID - e64037 AB - Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD. In a recent study, an increase in BDNF mRNA and protein levels was recorded in mice administered recombinant BDNF peripherally. Chronic, indwelling osmotic mini-pumps containing either recombinant BDNF or saline were surgically placed in R6/2 or wild-type mice from 4 weeks of age until euthanasia. Neurological evaluation (paw clasping, rotarod performance, locomotor activity in an open field) was performed. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that BDNF- treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. BDNF was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons. Moreover, systemically administered BDNF increased the synthesis of BDNF as demonstrated by RT-PCR, and this might account for the beneficial effects observed in this model. FAU - Giampa, Carmela AU - Giampa C AD - Laboratory of Neuroanatomy, Santa Lucia Foundation IRCCS Hospital at the European Center for Brain Research, Rome, Italy. FAU - Montagna, Elena AU - Montagna E FAU - Dato, Clemente AU - Dato C FAU - Melone, Mariarosa A B AU - Melone MA FAU - Bernardi, Giorgio AU - Bernardi G FAU - Fusco, Francesca Romana AU - Fusco FR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130520 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Neuroprotective Agents) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM EIN - PLoS One. 2016 Nov 23;11(11):e0166102. PMID: 27880782 MH - Animals MH - Brain-Derived Neurotrophic Factor/*administration & dosage/metabolism/pharmacokinetics MH - Cerebral Cortex/drug effects/metabolism MH - Corpus Striatum/drug effects/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Disease Models, Animal MH - Drug Evaluation, Preclinical MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Female MH - Gene Expression MH - Huntington Disease/*drug therapy/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Nerve Degeneration/drug therapy/metabolism MH - Neuroprotective Agents/*administration & dosage/metabolism/pharmacokinetics MH - Phosphorylation MH - Protein Processing, Post-Translational MH - Psychomotor Performance/drug effects MH - RNA, Messenger/genetics/metabolism MH - Recombinant Proteins/administration & dosage MH - Rotarod Performance Test PMC - PMC3659095 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/05/24 06:00 MHDA- 2013/12/25 06:00 PMCR- 2013/05/20 CRDT- 2013/05/24 06:00 PHST- 2012/11/02 00:00 [received] PHST- 2013/04/11 00:00 [accepted] PHST- 2013/05/24 06:00 [entrez] PHST- 2013/05/24 06:00 [pubmed] PHST- 2013/12/25 06:00 [medline] PHST- 2013/05/20 00:00 [pmc-release] AID - PONE-D-12-33914 [pii] AID - 10.1371/journal.pone.0064037 [doi] PST - epublish SO - PLoS One. 2013 May 20;8(5):e64037. doi: 10.1371/journal.pone.0064037. Print 2013.