PMID- 9706389
OWN - NLM
STAT- MEDLINE
DCOM- 19981112
LR  - 20190831
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 109
IP  - 1
DP  - 1998 Jul 1
TI  - Effects of gestational methylmercury exposure on immunoreactivity of specific 
      isoforms of PKC and enzyme activity during post-natal development of the rat 
      brain.
PG  - 33-49
AB  - Protein kinase C (PKC)-mediated phosphorylation has been implicated in neuronal 
      growth and differentiation [R.S. Turner, R.L. Mazzei, G.J. Raynor, P.R. Girard, 
      J.F. Kuo, Proc. Natl. Acad. Sci. U.S.A., 81 (1984) 3143-3147.]. We examined 
      effects of gestational exposure to the neurotoxicant, methylmercury (CH3Hg), on 
      the developmental profile of immunoreactivity (IR) for alpha, beta, gamma and 
      epsilon PKC isoforms and cytosolic PKC activity. Long-Evans dams were dosed on 
      gestational days (GD)6-15 (p.o.) with 0, 1, or 2 mg kg-1 day-1 CH3Hg dissolved in 
      saline. Pups were sacrificed and perfused with buffered paraformaldehyde on 
      post-natal days (PND) 1, 4, 10, 21, 45 and 85. The brains were sectioned 
      sagittally, stained immunohistochemically, and examined throughout the medial to 
      lateral extent. IR in neuronal cell bodies for PKC isoforms alpha, beta, gamma, 
      and epsilon was densest in the olfactory bulb, hippocampus, shell of the inferior 
      colliculus, pons, cerebral, piriform, and cerebellar cortex, whereas axonal 
      staining was prominent in the brainstem, internal capsule, corpus callosum, 
      anterior commissure, fornix and olfactory tract. In controls, the PKC alpha and 
      epsilon IR was highest on PND1-4, decreased dramatically by PND10, and decreased 
      further by PND21. In the neonate, the regional and cellular distributions of 
      alpha and epsilon IR were similar. The PKC gamma IR was greater at post-weaning 
      ages (PND21-85) with the greatest regional density apparent in the hippocampus, 
      cortex, and cerebellum. Only the highest dose of CH3Hg (2 mg kg-1 day-1; GD6-15) 
      produced a persistent decrease in regional alpha and epsilon, but not beta or 
      gamma IR during the post-natal period. These regional and time-dependent changes 
      in PKC isoforms were complemented by the examination of PKC activity in cortex, 
      olfactory bulb, cerebellum and brainstem. Cytosolic PKC activity increased from 
      PND1 to 10 in cortex, olfactory bulb, and cerebellum. On PND21, PKC activity 
      decreased in the cortex and olfactory bulb, but remained high in the cerebellum. 
      By contrast, PKC activity in the brainstem was highest on PND1 and 4 and 
      decreased dramatically by PND21. CH3Hg (2 mg kg-1 day-1) significantly decreased 
      PKC activity on PND1 and 4 in the cortex. The present results characterize the 
      cellular and regional ontogeny of PKC isoenzymes alpha, beta, gamma and epsilon, 
      and indicate that developmental exposure to CH3Hg can alter the ontogeny of 
      specific isoforms and regional PKC activity.
FAU - Haykal-Coates, N
AU  - Haykal-Coates N
AD  - National Health Effects and Ecological Research Laboratory, US Environmental 
      Protection Agency, Research Triangle Park, NC 27711, USA.
FAU - Shafer, T J
AU  - Shafer TJ
FAU - Mundy, W R
AU  - Mundy WR
FAU - Barone, S Jr
AU  - Barone S Jr
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res Dev Brain Res
JT  - Brain research. Developmental brain research
JID - 8908639
RN  - 0 (Isoenzymes)
RN  - 0 (Methylmercury Compounds)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/*drug effects/enzymology/growth & development
MH  - Cerebral Cortex/drug effects/enzymology/growth & development
MH  - Female
MH  - Hippocampus/drug effects/enzymology/growth & development
MH  - Immunohistochemistry
MH  - Isoenzymes/biosynthesis
MH  - Methylmercury Compounds/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Protein Kinase C/*biosynthesis
MH  - Rats
MH  - Rats, Long-Evans
EDAT- 1998/08/26 02:14
MHDA- 2001/03/28 10:01
CRDT- 1998/08/26 02:14
PHST- 1998/08/26 02:14 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/08/26 02:14 [entrez]
AID - S016538069800039X [pii]
AID - 10.1016/s0165-3806(98)00039-x [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 1998 Jul 1;109(1):33-49. doi: 
      10.1016/s0165-3806(98)00039-x.