PMID- 18627255
OWN - NLM
STAT- MEDLINE
DCOM- 20081020
LR  - 20211020
IS  - 0897-7151 (Print)
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Linking)
VI  - 25
IP  - 7
DP  - 2008 Jul
TI  - Agrin expression during synaptogenesis induced by traumatic brain injury.
PG  - 769-83
LID - 10.1089/neu.2008.0511 [doi]
AB  - Interaction between extracellular matrix proteins and regulatory proteinases can 
      mediate synaptic integrity. Previously, we documented that matrix 
      metalloproteinase 3 (MMP-3) expression and activity increase following traumatic 
      brain injury (TBI). We now report protein and mRNA analysis of agrin, a MMP-3 
      substrate, over the time course of trauma-induced synaptogenesis. Agrin 
      expression during the successful synaptic reorganization of unilateral entorhinal 
      cortical lesion (UEC) was compared with expression when normal synaptogenesis 
      fails (combined fluid percussion TBI and bilateral entorhinal lesion [BEC]). We 
      observed that agrin protein was increased in both models at 2 and 7 days 
      postinjury, and immuohistochemical (IHC) co-localization suggested reactive 
      astrocytes contribute to that increase. Agrin formed defined boundaries for 
      sprouting axons along deafferented dendrites in the UEC, but failed to do so 
      after combined insult. Similarly, Western blot analysis revealed greater increase 
      in UEC agrin protein relative to the combined TBI+BEC model. Both models showed 
      increased agrin transcription at 7 days postinjury and mRNA normalization by 15 
      days. Attenuation of synaptic pathology with the NMDA antagonist MK-801 reduced 
      7-day UEC agrin transcript to a level not different from unlesioned controls. By 
      contrast, MK-801 in the combined insult failed to significantly change 7-day 
      agrin transcript, mRNA levels remaining elevated over uninjured sham cases. 
      Together, these results suggest that agrin plays an important role in the 
      sprouting phase of reactive synaptogenesis, and that both its expression and 
      distribution are correlated with extent of successful recovery after TBI. 
      Further, when pathogenic conditions which induce synaptic plasticity are reduced, 
      increase in agrin mRNA is attenuated.
FAU - Falo, M Cristina
AU  - Falo MC
AD  - Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth 
      University Medical Center, Richmond, Virginia 23298, USA.
FAU - Reeves, Thomas M
AU  - Reeves TM
FAU - Phillips, Linda L
AU  - Phillips LL
LA  - eng
GR  - R01 NS044372/NS/NINDS NIH HHS/United States
GR  - NS-44372/NS/NINDS NIH HHS/United States
GR  - P30 NS-047463/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Agrin)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Agrin/genetics/*metabolism
MH  - Animals
MH  - Brain Injuries/drug therapy/metabolism/pathology/*physiopathology
MH  - Denervation
MH  - Disease Models, Animal
MH  - Dizocilpine Maleate/pharmacology
MH  - Entorhinal Cortex/injuries/*metabolism/ultrastructure
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Extracellular Matrix/genetics/metabolism
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Nerve Regeneration/*physiology
MH  - Neuronal Plasticity/*physiology
MH  - Neuroprotective Agents/pharmacology
MH  - Presynaptic Terminals/*metabolism/ultrastructure
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/metabolism
MH  - Up-Regulation/genetics
PMC - PMC2946878
EDAT- 2008/07/17 09:00
MHDA- 2008/10/22 09:00
PMCR- 2009/07/01
CRDT- 2008/07/17 09:00
PHST- 2008/07/17 09:00 [pubmed]
PHST- 2008/10/22 09:00 [medline]
PHST- 2008/07/17 09:00 [entrez]
PHST- 2009/07/01 00:00 [pmc-release]
AID - 10.1089/neu.2008.0511 [pii]
AID - 10.1089/neu.2008.0511 [doi]
PST - ppublish
SO  - J Neurotrauma. 2008 Jul;25(7):769-83. doi: 10.1089/neu.2008.0511.