PMID- 7854586
OWN - NLM
STAT- MEDLINE
DCOM- 19950316
LR  - 20071115
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 15
IP  - 3
DP  - 1994 Fall
TI  - Synaptic protein phosphorylation changes in animals exposed to neurotoxicants 
      during development.
PG  - 525-32
AB  - Protein phosphorylation represents a key process by which neuronal function is 
      regulated by first messengers interacting with extracellular membrane receptors. 
      Protein kinases transfer the phosphate group from ATP to neuron specific proteins 
      and phosphatases, catalyzing the removal of the phosphate group, shut off the 
      signal by restoring the reactive form of the protein. These phosphorylation 
      processes seem to be particularly important in long-term changes which follow 
      sustained activation of neurons. Particular importance has been given to the 
      Calcium/phospholipid-dependent protein kinase (PKC) as the molecular mechanism in 
      synaptic plasticity associated with learning and memory. We have studied the 
      changes of PKC activity in an animal model of impaired cognitive functions as a 
      consequence of an exposure during embryonic life to an antimitotic agent, 
      methylazoxy-methanol acetate (MAM). Treatment at gestational day (GD) 15 results 
      in offspring showing a dose-dependent reduction in the size of cortex and 
      hippocampus. When adult, these animals show impairments in several tests for 
      learning and memory. In hippocampal slice preparations from MAM-treated rats, 
      Long-Term Potentiation could not be induced in the CA1 region, the area affected 
      by the treatment. However, in the hippocampal dentate gyrus, an area not affected 
      by the treatment, LTP could be induced. Moreover, these animals show 
      area-specific changes in the phosphorylation state of the protein B-50/GAP-43, a 
      well characterized neuron specific substrate for PKC. By changing the time of MAM 
      exposure, i.e. at GD19, a different pattern of brain damage occurs and this 
      results both in a different pattern in behavior and B-50 
      phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Di Luca, M
AU  - Di Luca M
AD  - Institute of Pharmacological Sciences, University of Milano, Italy.
FAU - Caputi, A
AU  - Caputi A
FAU - Cattabeni, F
AU  - Cattabeni F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (GAP-43 Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Phosphoproteins)
RN  - 592-62-1 (Methylazoxymethanol Acetate)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Fetus/*drug effects
MH  - GAP-43 Protein
MH  - Membrane Glycoproteins/*metabolism
MH  - Methylazoxymethanol Acetate/toxicity
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neuronal Plasticity
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/physiology
RF  - 43
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
PST - ppublish
SO  - Neurotoxicology. 1994 Fall;15(3):525-32.