PMID- 23159315
OWN - NLM
STAT- MEDLINE
DCOM- 20130606
LR  - 20220310
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 229
DP  - 2013 Jan 15
TI  - Failure of axonal transport induces a spatially coincident increase in astrocyte 
      BDNF prior to synapse loss in a central target.
PG  - 55-70
LID - S0306-4522(12)01098-6 [pii]
LID - 10.1016/j.neuroscience.2012.10.069 [doi]
AB  - Failure of anterograde transport to distal targets in the brain is a common 
      feature of neurodegenerative diseases. We have demonstrated in rodent models of 
      glaucoma, the most common optic neuropathy, early loss of anterograde transport 
      along the retinal ganglion cell (RGC) projection to the superior colliculus (SC) 
      is retinotopic and followed by a period of persistence of RGC axon terminals and 
      synapses through unknown molecular pathways. Here we use the DBA/2J mouse model 
      of hereditary glaucoma and an acute rat model to demonstrate that retinotopically 
      focal transport deficits in the SC are accompanied by a spatially coincident 
      increase in brain-derived neurotrophic factor (BDNF), especially in hypertrophic 
      astrocytes. These neurochemical changes occur prior to loss of RGC synapses in 
      the DBA/2J SC. In contrast to BDNF protein, levels of Bdnf mRNA decreased with 
      transport failure, even as mRNA encoding synaptic structures remained unchanged. 
      In situ hybridization signal for Bdnf mRNA was the strongest in SC neurons, and 
      labeling for the immature precursor pro-BDNF was very limited. Subcellular 
      fractionation of SC indicated that membrane-bound BDNF decreased with age in the 
      DBA/2J, while BDNF released from vesicles remained high. These results suggest 
      that in response to diminished axonal function, activated astrocytes in the brain 
      may sequester mature BDNF released from target neurons to counter stressors that 
      otherwise would challenge survival of projection synapses.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Crish, S D
AU  - Crish SD
AD  - The Vanderbilt Eye Institute, Vanderbilt University Medical Center, 11425 
      Langford Medical Research Building IV, 2213 Garland Avenue, Nashville, TN 37232, 
      USA. scrish@neoucom.edu
FAU - Dapper, J D
AU  - Dapper JD
FAU - MacNamee, S E
AU  - MacNamee SE
FAU - Balaram, P
AU  - Balaram P
FAU - Sidorova, T N
AU  - Sidorova TN
FAU - Lambert, W S
AU  - Lambert WS
FAU - Calkins, D J
AU  - Calkins DJ
LA  - eng
GR  - P30 EY008126/EY/NEI NIH HHS/United States
GR  - P30EY008126/EY/NEI NIH HHS/United States
GR  - R01 EY022358/EY/NEI NIH HHS/United States
GR  - EY017427/EY/NEI NIH HHS/United States
GR  - R01 EY017427/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121114
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Axonal Transport/*physiology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Disease Models, Animal
MH  - Glaucoma/genetics/*metabolism
MH  - Mice
MH  - Optic Nerve Diseases/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Retinal Ganglion Cells/*metabolism
MH  - Superior Colliculi/metabolism
MH  - Synapses/*metabolism
MH  - Visual Pathways/metabolism
PMC - PMC3534890
MID - NIHMS422378
COIS- DISCLOSURE STATEMENT The authors have no conflicts of interest to disclose.
EDAT- 2012/11/20 06:00
MHDA- 2013/06/07 06:00
PMCR- 2014/01/15
CRDT- 2012/11/20 06:00
PHST- 2012/07/10 00:00 [received]
PHST- 2012/10/04 00:00 [revised]
PHST- 2012/10/24 00:00 [accepted]
PHST- 2012/11/20 06:00 [entrez]
PHST- 2012/11/20 06:00 [pubmed]
PHST- 2013/06/07 06:00 [medline]
PHST- 2014/01/15 00:00 [pmc-release]
AID - S0306-4522(12)01098-6 [pii]
AID - 10.1016/j.neuroscience.2012.10.069 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Jan 15;229:55-70. doi: 10.1016/j.neuroscience.2012.10.069. 
      Epub 2012 Nov 14.