PMID- 17052708
OWN - NLM
STAT- MEDLINE
DCOM- 20070320
LR  - 20131121
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 203
IP  - 2
DP  - 2007 Feb
TI  - Progesterone modulates brain-derived neurotrophic factor and choline 
      acetyltransferase in degenerating Wobbler motoneurons.
PG  - 406-14
AB  - Progesterone (PROG) shows neuroprotective effects in nervous system diseases. The 
      Wobbler mouse, a model of motoneuron degeneration, suffers a mutation of the 
      Vsp154 gene on chromosome 11 leading to motoneuron vacuolation and astrocytosis 
      of the spinal cord. Previous work has demonstrated beneficial effects of PROG in 
      the Wobbler mouse. As an extension of this work, we now studied steroid effects 
      on neuronal brain-derived neurotrophic factor (BDNF) mRNA and protein, on choline 
      acetyltransferase (ChAT) immunoreactivity (IR) and activity in the spinal cord, 
      and on recovery of muscle atrophy. Wobbler mice received implants of PROG pellets 
      (20 mg) at 6 and 10 weeks of age and were killed at 14 weeks. In situ 
      hybridization for BDNF mRNA demonstrated that grain density in large (>600 
      microm2) and medium size (<600 microm2) ventral horn neurons was decreased in 
      untreated Wobblers, whereas PROG treatment increased BDNF mRNA in both neuronal 
      types. PROG also induced a subcellular redistribution of BDNF protein, which in 
      controls and steroid-naive Wobblers showed a predominant perinuclear and 
      nucleolar location, whereas after PROG treatment, it was detected in cytoplasmic 
      aggregates. ChAT activity was reduced by 55.3% in muscles of untreated Wobbler 
      mice, whereas a significant increment was obtained after PROG treatment. Wobblers 
      also showed reduced number of ChAT positive motoneurons, but this number was 
      restored to normal by PROG. Finally, the pronounced biceps atrophy of 
      steroid-naive Wobbler mice was slightly but significantly increased by 
      PROG-treatment. Considering the important role played by neurotrophins on 
      neuronal function, changes in BDNF might be part of the PROG activated-pathways 
      to provide neuroprotection and re-establish neurotransmission and neuromuscular 
      function in this degeneration model.
FAU - Gonzalez Deniselle, Maria Claudia
AU  - Gonzalez Deniselle MC
AD  - Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina 
      Experimental, and Dep. of Biochemistry, Faculty of Medicine, University of Buenos 
      Aires, Argentina.
FAU - Garay, Laura
AU  - Garay L
FAU - Gonzalez, Susana
AU  - Gonzalez S
FAU - Saravia, Flavia
AU  - Saravia F
FAU - Labombarda, Florencia
AU  - Labombarda F
FAU - Guennoun, Rachida
AU  - Guennoun R
FAU - Schumacher, Michael
AU  - Schumacher M
FAU - De Nicola, Alejandro F
AU  - De Nicola AF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061017
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*metabolism
MH  - Choline O-Acetyltransferase/*metabolism
MH  - Fluorescent Antibody Technique
MH  - In Situ Hybridization
MH  - Mice
MH  - Mice, Neurologic Mutants
MH  - Motor Neurons/drug effects/metabolism
MH  - Nerve Degeneration/metabolism/*physiopathology
MH  - Progesterone/pharmacology/*physiology
MH  - RNA, Messenger/biosynthesis
MH  - Spinal Cord/metabolism/pathology
EDAT- 2006/10/21 09:00
MHDA- 2007/03/21 09:00
CRDT- 2006/10/21 09:00
PHST- 2006/05/23 00:00 [received]
PHST- 2006/08/11 00:00 [revised]
PHST- 2006/08/24 00:00 [accepted]
PHST- 2006/10/21 09:00 [pubmed]
PHST- 2007/03/21 09:00 [medline]
PHST- 2006/10/21 09:00 [entrez]
AID - S0014-4886(06)00526-7 [pii]
AID - 10.1016/j.expneurol.2006.08.019 [doi]
PST - ppublish
SO  - Exp Neurol. 2007 Feb;203(2):406-14. doi: 10.1016/j.expneurol.2006.08.019. Epub 
      2006 Oct 17.