PMID- 10411342
OWN - NLM
STAT- MEDLINE
DCOM- 19990727
LR  - 20190513
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 58
IP  - 7
DP  - 1999 Jul
TI  - Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic
      glutamate-mediated neurodegeneration.
PG  - 719-28
AB  - Although pigment epithelium-derived factor (PEDF) is a neurotrophic factor that
      may aid the development, differentiation, and survival of adjacent neural
      retinae, the wider distribution of PEDF mRNA in the central nervous system
      suggested to us that this factor could have pleiotropic neurotrophic and
      neuroprotective effects on nonretinal neurons. We examined the distribution of
      PEDF mRNA and its transcript in the spinal cord. By immunohistochemistry and
      western blot analysis using an antihuman PEDF antiserum of known specificity, we 
      found that PEDF protein is present in spinal cord, cerebrospinal fluid, and
      skeletal muscle and that its mRNA appears concentrated in motor neurons of the
      human spinal cord. These observations indicate that PEDF could have potential
      autocrine and paracrine effects on motor neurons, as well as being
      target-derived. We analyzed the pharmacologic utility of PEDF in a postnatal
      organotypic culture model of motor neuron degeneration and proved it is highly
      neuroprotective. The effect was biologically important, significantly sparing the
      spinal cord's gross organotypic morphological appearance and preserving motor
      neuron choline acetyltransferase (ChAT). PEDF alone did not increase ChAT,
      indicating that the observed effect is neuroprotective, not merely an
      upregulation of motor neuron ChAT. Further, PEDF preserved motor neuron number,
      proving a survival effect. We hypothesize that PEDF may play important roles in
      the survival and maintenance of spinal motor neurons in their neuroprotection
      against acquired insults in postnatal life. It should be developed further as a
      therapeutic strategy for motor neuron diseases such as amyotrophic lateral
      sclerosis (ALS).
FAU - Bilak, M M
AU  - Bilak MM
AD  - Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Corse, A M
AU  - Corse AM
FAU - Bilak, S R
AU  - Bilak SR
FAU - Lehar, M
AU  - Lehar M
FAU - Tombran-Tink, J
AU  - Tombran-Tink J
FAU - Kuncl, R W
AU  - Kuncl RW
LA  - eng
GR  - KO8NS01722/NS/NINDS NIH HHS/United States
GR  - R01NS33985/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Eye Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serpins)
RN  - 0 (pigment epithelium-derived factor)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Survival/physiology
MH  - Cerebrospinal Fluid/metabolism
MH  - Choline O-Acetyltransferase/metabolism
MH  - Chronic Disease
MH  - Ependyma/metabolism
MH  - *Eye Proteins
MH  - Female
MH  - *Glutamic Acid/poisoning
MH  - Haplorhini
MH  - Humans
MH  - Motor Neurons/*drug effects/metabolism/pathology
MH  - Muscle, Skeletal/metabolism
MH  - Nerve Degeneration/*chemically induced/*pathology
MH  - *Nerve Growth Factors
MH  - Neuroprotective Agents/*pharmacology
MH  - Organ Culture Techniques
MH  - Proteins/genetics/metabolism/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Serpins/genetics/metabolism/*pharmacology
MH  - Spinal Cord/cytology/metabolism
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - 10.1097/00005072-199907000-00006 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 1999 Jul;58(7):719-28. doi:
      10.1097/00005072-199907000-00006.