Developmental Models of Brain Dysfunctions Induced by Targeted Cellular
Ablations With Methylazoxymethanol.
Cattabeni, Flaminio, and Monica Di Luca.
Institute of Pharmacalogical Science, University of Milano, Milan,
Italy.
APStracts 2:0044P, 1996.
ABSTRACT
Abnormal brain development represents one of the major causes of neurological
disorders in humans, and determining the factors responsible for generating
specific brain malformations represents a formidable task for developmental
neurobiology. The knowledge of the precise neurogenetic time table and the use
of toxins, like methylazoxymethanol, able to interfere with neuroepithelial
cells entering their last mitotic cycle, have allowed for targeted neuronal
ablations in specific brain areas of the central nervous system (CNS) when
administered at different gestational or postnatal days in various animal
species. Of particular relevance are the studies in which ablations of
neuronal populations of cortex, hippocampus, and cerebellum have been made.
The results obtained show that these early ablations induce a number of
neuroanatomic, neurochemical, and electrophysiological changes that give us
the possibility to unravel the biochemical strategies utilized by surviving
neurons to adapt to the perturbated environment. Most striking are the
findings that target deprivation does not affect the survival of afferent
neurons in the CNS (except for neurons of the lateral geniculate nucleus), in
sharp contrast to the notion of target dependence for peripheral nervous
system neurons. Animals showing selective ablations in the Ammon's horn of the
hippocampus allow us to understand the complex biochemical pathways leading to
changes in activity-dependent synaptic plasticity, and the data underscore the
fundamental role of diverse Ca[sup]2+[r]-dependent protein kinases, and their
substrates, in modulating pre- and postsynaptic events during induction and
maintenance of long-term potentiation (LTP). Because LTP represents a useful
model to study molecular substrates of learning and memory, this animal model
might be of relevance in understanding cognitive brain dysfunctions.
APS Manuscript Number P26-6.
Article publication pending January 1997, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996