PMID- 24551172
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 2
DP  - 2014
TI  - Overexpression of BDNF increases excitability of the lumbar spinal network and 
      leads to robust early locomotor recovery in completely spinalized rats.
PG  - e88833
LID - 10.1371/journal.pone.0088833 [doi]
LID - e88833
AB  - Strategies to induce recovery from lesions of the spinal cord have not fully 
      resulted in clinical applications. This is a consequence of a number of 
      impediments that axons encounter when trying to regrow beyond the lesion site, 
      and that intraspinal rearrangements are subjected to. In the present study we 
      evaluated (1) the possibility to improve locomotor recovery after complete 
      transection of the spinal cord by means of an adeno-associated (AAV) viral vector 
      expressing the neurotrophin brain-derived neurotrophic factor (BDNF) in lumbar 
      spinal neurons caudal to the lesion site and (2) how the spinal cord transection 
      and BDNF treatment affected neurotransmission in the segments caudal to the 
      lesion site. BDNF overexpression resulted in clear increases in expression levels 
      of molecules involved in glutamatergic (VGluT2) and GABAergic (GABA, GAD65, 
      GAD67) neurotransmission in parallel with a reduction of the potassium-chloride 
      co-transporter (KCC2) which contributes to an inhibitory neurotransmission. BDNF 
      treated animals showed significant improvements in assisted locomotor 
      performance, and performed locomotor movements with body weight support and 
      plantar foot placement on a moving treadmill. These positive effects of BDNF 
      local overexpression were detectable as early as two weeks after spinal cord 
      transection and viral vector application and lasted for at least 7 weeks. 
      Gradually increasing frequencies of clonic movements at the end of the experiment 
      attenuated the quality of treadmill walking. These data indicate that BDNF has 
      the potential to enhance the functionality of isolated lumbar circuits, but also 
      that BDNF levels have to be tightly controlled to prevent hyperexcitability.
FAU - Ziemlinska, Ewelina
AU  - Ziemlinska E
AD  - Nencki Institute of Experimental Biology, Warsaw, Poland.
FAU - Kugler, Sebastian
AU  - Kugler S
AD  - Center of Molecular Physiology of the Brain, University of Gottingen, Gottingen, 
      Germany.
FAU - Schachner, Melitta
AU  - Schachner M
AD  - Center for Neuroscience, Shantou University Medical College, Shantou, China.
FAU - Wewior, Iwona
AU  - Wewior I
AD  - Nencki Institute of Experimental Biology, Warsaw, Poland.
FAU - Czarkowska-Bauch, Julita
AU  - Czarkowska-Bauch J
AD  - Nencki Institute of Experimental Biology, Warsaw, Poland.
FAU - Skup, Malgorzata
AU  - Skup M
AD  - Nencki Institute of Experimental Biology, Warsaw, Poland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140214
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Symporters)
RN  - 0 (Vesicular Glutamate Transport Proteins)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 1)
RN  - TE7660XO1C (Glycine)
SB  - IM
EIN - PLoS One. 2014;9(3):e92439
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/*therapeutic use
MH  - Dependovirus/metabolism
MH  - Genetic Vectors/metabolism
MH  - Glutamate Decarboxylase/genetics/metabolism
MH  - Glycine/metabolism
MH  - Green Fluorescent Proteins/metabolism
MH  - Lumbar Vertebrae/enzymology/pathology/*physiopathology
MH  - Male
MH  - *Motor Activity
MH  - RNA, Messenger/genetics/metabolism
MH  - Range of Motion, Articular
MH  - Rats
MH  - Rats, Wistar
MH  - *Recovery of Function
MH  - Spinal Cord Injuries/metabolism/*physiopathology/*therapy
MH  - Symporters/metabolism
MH  - Thoracic Vertebrae/pathology/physiopathology
MH  - Transduction, Genetic
MH  - Vesicular Glutamate Transport Proteins/genetics/metabolism
MH  - gamma-Aminobutyric Acid/metabolism
MH  - K Cl- Cotransporters
PMC - PMC3925164
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/02/20 06:00
MHDA- 2014/10/22 06:00
PMCR- 2014/02/14
CRDT- 2014/02/20 06:00
PHST- 2013/02/25 00:00 [received]
PHST- 2014/01/16 00:00 [accepted]
PHST- 2014/02/20 06:00 [entrez]
PHST- 2014/02/20 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
PHST- 2014/02/14 00:00 [pmc-release]
AID - PONE-D-13-08277 [pii]
AID - 10.1371/journal.pone.0088833 [doi]
PST - epublish
SO  - PLoS One. 2014 Feb 14;9(2):e88833. doi: 10.1371/journal.pone.0088833. eCollection 
      2014.