Microencephaly reduces the phosphorylation of the PKC substrate B-50/GAP43 in rat cortex and hippocampus.
The administration of the antimitotic agent methylazoxymethanol (MAM) to rats at day 15 of gestation results in a consistent loss of intrinsic neurons primarily in cortex and hippocampus. These animals when adult, show a cognitive impairment, if tested in specific behavioural tasks. B-50/GAP43 is a neuronal phosphoprotein, specific substrate for protein kinase C (PKC) and involved in the development and plasticity of synaptic connections. Since B-50/GAP43 has been implicated in functional modulation of synapses and in the molecular mechanism underlying cognitive processes, we studied the phosphorylation of B-50 in cortex and hippocampus of control and MAM-treated rats. Here we report that B-50 in MAM-treated rats shows a marked reduction in the phosphate incorporation in the areas affected by the prenatal treatment. In situ hybridization studies demonstrate that the mRNA levels for B-50 are not altered in MAM-treated rats and that the relative amount of the protein, as revealed by Western blot analysis, is also not affected in microencephalic rats. These results suggest that microencephalic animals might represent a useful experimental model to study biochemical correlates of cognitive impairment and synaptic plasticity.
Di Luca
M
M
Institute of Pharmacological Sciences, University of Milan, Italy.
Cimino
M
M
De Graan
P N
PN
Oestreicher
A B
AB
Gispen
W H
WH
Cattabeni
F
F
D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D019922:GAP-43 Protein; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013574:Synaptosomes / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D010750:Phosphoproteins; D008746:Methylazoxymethanol Acetate; D011493:Protein Kinase C