NEUROTOXICANT EFFECTS ON CELL CYCLE REGULATION OF NEUROGENESIS

  • Reuhl, Kenneth (PI)
  • Lioy, Paul (PI)
  • Lambert, George (PI)
  • CICCO-BLOOM, EMANUEL DI (PI)
  • WAGNER, GEORGE (PI)
  • LAMBERT (PI)
  • REUHL, KENNETH REYNOLDS (PI)

Project Details

Description

DESCRIPTION (provided by applicant)
The investigators hypothesize that neurotoxic metals and teratogens disrupt
neurogenesis in developing forebrain and hindbrain systems in vitro and in
vivo, acting to inhibit proliferation by altering mitogenic growth factor
receptors and cell cycles signaling pathways.
There are increasing numbers of children who experience problems with
learning, social interactions, and self-regulation, and exhibit difficulties
with fine and gross motor control. Normal brain development depends on
interactions among multiple factors including those from genetic,
neurochemical, biochemical, social, and environmental sources. Significantly,
recent studies indicate that environmental toxicants injure the developing
brain, potentially contributing to cognitive and motor deficits. Toxicants
affecting the brain, neurotoxicants, may act at multiple time windows,
eliciting immediate stage-dependent effects in specific systems that influence
subsequent ontogenetic processes as well. However, while negative effects of
neurotoxicants on cell migration, differentiation, and survival have been
well-characterized, little is known about the effects on the generation of
neurons (neurgenesis) and underlying pathogenetic mechanisms.
As child neurologists, the investigators frequently evaluate children for
abnormal brain development in clinic, concerned about attention, learning,
behavior, and autism spectrum disorders. Further, as a member of the
Scientific Advisory Board of the National Alliance for Autism Research (NAAR),
a community family advocacy organization, they provide targeted basic and
clinical research support. This current proposal represents a new direction
for basic research in the investigators laboratory, which has focused on
defining mechanisms that control generation of distinct neuronal populations
from dividing precursors. Previously, they examined both positive and
negative regulators of precursor proliferation in the developing nervous
system, defining growth factor and neuropeptide effects in culture and in
vivo. Further, they employed neuronal populations in forebrain and hindbrain
regions involved in learning, memory and motor functions in the fetus as well
as the developing postnatal animal. Based on extensive studies, the
investigators now turn attention to the effects of well-characterized
neurotoxicants, including lead and mercury, and model teratogen, valproic
acid, on neurogenesis in the embryo and the newborn, defining mediating
mitogenic and cell cycle pathways and designing new model systems.
StatusFinished
Effective start/end date1/1/018/31/06

ASJC

  • Psychiatry and Mental health
  • Neuropsychology and Physiological Psychology
  • Genetics
  • Behavioral Neuroscience
  • Cell Biology