PMID- 18571429
OWN - NLM
STAT- MEDLINE
DCOM- 20081029
LR  - 20080825
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 39
IP  - 1
DP  - 2008 Sep
TI  - Blood level of brain-derived neurotrophic factor mRNA is progressively reduced in 
      rodent models of Huntington's disease: restoration by the neuroprotective 
      compound CEP-1347.
PG  - 1-7
LID - 10.1016/j.mcn.2008.04.012 [doi]
AB  - Huntington's disease (HD) is an age-related neurodegenerative disorder that is 
      currently untreatable. A prominent feature of HD pathology is the reduction of 
      the pro-survival neurotrophin Brain-Derived Neurotrophic Factor (BDNF). Both mRNA 
      and protein levels of BDNF are decreased in the brains of several HD rodent 
      models and in human HD patients. We now report for the first time that this 
      molecular event is mirrored in blood from HD rodent models. While protein levels 
      of BDNF are undetectable in mouse blood, mRNA levels are measurable and diminish 
      during HD progression in transgenic mouse (R6/2) and rat models of HD. Among the 
      eight different BDNF transcripts, only BDNF exon III is transcribed in mouse 
      blood and its expression is progressively compromised in R6/2 mice with respect 
      to age-matched wild-types. Assessment of BDNF mRNA in HD rat blood shows a 
      similar result, which is reinforced by evidence that protein levels of the 
      neurotrophin are also significantly reduced at a symptomatic stage. Finally, we 
      demonstrate that acute and chronic treatment of R6/2 mice with CEP-1347, a mixed 
      lineage kinase (MLK) inhibitor with neuroprotective and neurotrophic effects, 
      leads to increased total BDNF mRNA in blood when compared to untreated R6/2 mice. 
      Our results indicate that alterations in BDNF mRNA levels in peripheral blood are 
      a readily accessible measurement of disease progression and drug efficacy in HD 
      rodent models.
FAU - Conforti, Paola
AU  - Conforti P
AD  - Department of Pharmacological Sciences and Center for Stem Cell Research, 
      University of Milan, Via Balzaretti 9, 20133 Milano, Italy.
FAU - Ramos, Catarina
AU  - Ramos C
FAU - Apostol, Barbara L
AU  - Apostol BL
FAU - Simmons, Danielle A
AU  - Simmons DA
FAU - Nguyen, Huu Phuc
AU  - Nguyen HP
FAU - Riess, Olaf
AU  - Riess O
FAU - Thompson, Leslie Michels
AU  - Thompson LM
FAU - Zuccato, Chiara
AU  - Zuccato C
FAU - Cattaneo, Elena
AU  - Cattaneo E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080510
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Messenger)
RN  - 156177-65-0 (3,9-bis((ethylthio)methyl)-K-252a)
SB  - IM
MH  - Animals
MH  - *Brain-Derived Neurotrophic Factor/blood/genetics
MH  - Carbazoles/*metabolism/therapeutic use
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Enzyme Inhibitors/metabolism/therapeutic use
MH  - Exons
MH  - Humans
MH  - Huntington Disease/*blood/drug therapy/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Neuroprotective Agents/*metabolism/therapeutic use
MH  - RNA, Messenger/*blood
MH  - Rats
EDAT- 2008/06/24 09:00
MHDA- 2008/10/31 09:00
CRDT- 2008/06/24 09:00
PHST- 2007/12/07 00:00 [received]
PHST- 2008/03/28 00:00 [revised]
PHST- 2008/04/04 00:00 [accepted]
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2008/10/31 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - S1044-7431(08)00104-8 [pii]
AID - 10.1016/j.mcn.2008.04.012 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2008 Sep;39(1):1-7. doi: 10.1016/j.mcn.2008.04.012. Epub 2008 
      May 10.