PMID- 12504884
OWN - NLM
STAT- MEDLINE
DCOM- 20030121
LR  - 20190722
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 178
IP  - 2
DP  - 2002 Dec
TI  - Tyrosine phosphatase inhibition enhances neurotrophin potency and rescues 
      nigrostriatal neurons in adult rats.
PG  - 259-67
AB  - Neurotrophic factors regulate a variety of cellular processes, including neuronal 
      survival during development and after injury. For instance, brain-derived 
      neurotrophic factor (BDNF) can prevent the death of dopaminergic substantia nigra 
      neurons in rats. Most neurotrophic factor receptors, such as TrkB for BDNF, are 
      tyrosine kinases whose signaling is terminated by protein tyrosine phosphatases 
      (PTPs). We tested the idea that inhibition of PTPs, and thus potentially 
      enhancement of the efficiency of endogenous trophic factors and their receptors, 
      would lead to increased neuronal survival. After a 2-week infusion of the small 
      PTP inhibitor molecule peroxovanadium (pVa, pervanadate) close to the substantia 
      nigra of adult rats, up to 66% of axotomized substantia nigra neurons had 
      survived, compared to only 33% in control rats infused with PBS. PVa most likely 
      affected TrkB and/or downstream signaling molecules, as ineffective doses of BDNF 
      and pVa had a synergistic effect when given simultaneously, rescuing 82% of the 
      neurons. PVa stimulated tyrosine hydroxylase (TH) expression in the noninjured 
      substantia nigra but did not prevent axotomy-induced loss of TH. These results 
      raise the possibility that PTP inhibition can prevent neuronal death by enhancing 
      neurotrophic factor signaling pathways in the adult mammalian nervous system, 
      identifies an important role for PTPs in neuronal functioning, and points to a 
      novel small molecule treatment approach for neurologic disorders
FAU - Lu, X
AU  - Lu X
AD  - Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova 
      Scotia, Canada.
FAU - Maysinger, D
AU  - Maysinger D
FAU - Hagg, T
AU  - Hagg T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (peroxovanadate)
RN  - 3WHH0066W5 (Vanadates)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects/physiology
MH  - Corpus Striatum/drug effects/*enzymology
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Injections, Intraventricular
MH  - Nerve Growth Factors/*physiology
MH  - Neurons/drug effects/*enzymology
MH  - Parkinsonian Disorders/enzymology
MH  - Protein Tyrosine Phosphatases/*antagonists & inhibitors/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/physiology
MH  - Signal Transduction/physiology
MH  - Substantia Nigra/drug effects/*enzymology
MH  - Vanadates/administration & dosage
EDAT- 2002/12/31 04:00
MHDA- 2003/01/22 04:00
CRDT- 2002/12/31 04:00
PHST- 2002/12/31 04:00 [pubmed]
PHST- 2003/01/22 04:00 [medline]
PHST- 2002/12/31 04:00 [entrez]
AID - S0014488602980428 [pii]
AID - 10.1006/exnr.2002.8042 [doi]
PST - ppublish
SO  - Exp Neurol. 2002 Dec;178(2):259-67. doi: 10.1006/exnr.2002.8042.