PMID- 12835095
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20031112
LR  - 20230320
IS  - 1029-8428 (Print)
IS  - 1029-8428 (Linking)
VI  - 1
IP  - 4
DP  - 2000 Apr
TI  - Gestational exposure to methylmercury alters neurotrophin- and 
      carbachol-stimulated phosphatidylinositide hydrolysis in cerebral cortex of 
      neonatal rats.
PG  - 271-83
AB  - Neurotrophin-stimulated signal transduction through the Trk receptors has been 
      implicated in the development and survival of the nervous system. Phospholipase 
      Cgamma (PLCgamma) is an early downstream effector for the Trk receptors, and 
      catalyzes the hydrolysis of phosphatidylinositides (PI) to inositol phosphates 
      (IPs) and diacylglycerol. The current study demonstrated that PI hydrolysis can 
      be used as a measure of Trk stimulation in slices from neonatal rat brain, and 
      examined changes in the ontogeny of neurotrophin-stimulated PI hydrolysis in 
      animals exposed to MeHg during gestation. Neurotrophin-3 (NT-3) and brain-derived 
      neurotrophic factor (BDNF) stimulated PI hydrolysis in neocortical and cerebellar 
      slices from neonatal rats in a concentration-dependent manner (30-1000 ng/ml). 
      The neurotrophin-stimulated PI hydrolysis was completely blocked by K-252a, a 
      compound known to inhibit Trk autophosphorylation. To examine the effects of MeHg 
      on PI hydrolysis, Long-Evans dams were dosed p.o. on gestational days 6-15 with 0 
      or 2 mg/kg/day MeHg dissolved in saline. Pups were sacrificed on postnatal days 
      (PND) 1, 4, 10, 14, and 21 and brain slices prepared from the neocortex and 
      cerebellum. Neurotrophin-stimulated PI hydrolysis was highest on PND 1-4 and 
      decreased with age in slices from both regions. Prior exposure to MeHg had no 
      effect on NT-3 or BDNF-stimulated PI hydrolysis in the cerebellum; however, in 
      the neocortex carbachol-stimulated PI hydrolysis and NT-3-stimulated PI 
      hydrolysis were decreased on PND 1. In addition, NT-3-stimulated PI hydrolysis 
      was increased on PND 14 compared to controls. Nerve growth factor (NGF), which 
      had no effect in controls, increased PI hydrolysis in MeHg exposed animals. Acute 
      exposure to 10 micro M MeHg increased basal PI hydrolysis in cortical slices and 
      increased NT-3- and BDNF-stimulated PI hydrolysis in slices from the cerebellum. 
      These data indicate that gestational exposure to MeHg can alter neurotrophin 
      signaling in the neocortex at early postnatal times.
FAU - Mundy, W M
AU  - Mundy WM
AD  - Neurotoxicology Division, National Health and Environmental Effects Research 
      Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 
      27711, USA. mundy.william@epamail.epa.gov
FAU - Parran, D
AU  - Parran D
FAU - Barone, S Jr
AU  - Barone S Jr
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
EDAT- 2003/07/02 05:00
MHDA- 2003/07/02 05:01
CRDT- 2003/07/02 05:00
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2003/07/02 05:01 [medline]
PHST- 2003/07/02 05:00 [entrez]
AID - 10.1007/BF03033257 [doi]
PST - ppublish
SO  - Neurotox Res. 2000 Apr;1(4):271-83. doi: 10.1007/BF03033257.