Inhibition of progenitor cell proliferation in the dentate gyrus of rats following post-weaning lead exposure.

Although lead is a potent developmental neurotoxin, the effects of postnatal lead exposure on progenitor cell proliferation in the hippocampus has not been examined. Postnatal day 25 rats were fed a lead containing diet (1500 ppm lead acetate) for 30-35 days and administered bromodeoxyuridine (BrdU, 50 mg/kg, i.p.

Enriched environment during development is protective against lead-induced neurotoxicity.

It is known that children of lower socioeconomic status have a disproportionately higher risk of being exposed to lead and have a more negative outcome from that exposure than children who are raised under more fortunate circumstances. Yet, little is known about how environmental factors may influence the injurious effects on the brain of a neurotoxin such as lead. The present study used an animal model of lead poisoning to examine the extent to which different environmental milieus may modify the effects of lead on the developing brain.

Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease.

Hyperphosphorylated tau, which is the major protein of the neurofibrillary tangles in Alzheimer's disease brain, is most probably the result of an imbalance of tau kinase and phosphatase activities in the affected neurons. By using metabolically competent rat brain slices as a model, we found that selective inhibition of protein phosphatase 2A by okadaic acid induced an Alzheimer-like hyperphosphorylation and accumulation of tau. The hyperphosphorylated tau had a reduced ability to bind to microtubules and to promote microtubule assembly in vitro.

Regulation of phosphorylation of neuronal microtubule-associated proteins MAP1b and MAP2 by protein phosphatase-2A and -2B in rat brain.

The function of the neuronal high molecular weight microtubule-associated proteins (MAPs) MAP1b and MAP2 is regulated by the degree of their phosphorylation, which in turn is controlled by the activities of protein kinases and protein phosphatases (PP). To investigate the role of PP in the regulation of the phosphorylation of MAP1b and MAP2, we used okadaic acid and cyclosporin A to selectively inhibit PP2A and PP2B activities, respectively, in metabolically competent rat brain slices. The alteration of the phosphorylation levels of MAP1b and MAP2 was examined by Western blots using several phosphorylation-dependent antibodies to these proteins.

Antipsychotic drug effects on glutamatergic activity.

Previous work from this laboratory indicated that some antipsychotic drugs possess unique action at N-methyl-D-aspartate (NMDA) receptors. A functional neurochemical assay showed that, at concentrations similar to those found in the cerebrospinal fluid (CSF) of schizophrenics, antipsychotic drugs augment NMDA activity while, at higher concentrations, NMDA activity is suppressed. Using similar analysis, the present paper reports that this pattern of response is also shown by the antipsychotic drugs thioridazine and chlorpromazine.