The vulnerability of the developing central nervous system to insults of maternal vitamin B-6 undernutrition has received increased attention in recent years. Our work and that of others has shown that inadequate vitamin B-6 nutrition during brain developments leads to neurochemical modifications in the synaptic environment of various neurotransmitter systems in the brain of progeny. An increasing body experimental evidence indicates that perturbations in synaptic neurochemistry are related to a variety of behavioral and neuropsychiatric conditions. Our work using an animal model of inadequate maternal vitamin B-6 nutrition produces major alterations in the ontogenesis of several neurotransmitter systems in the offspring. These studies also show that for some neurotransmitter systems (e.g. the GABAergic system in the cerebellum), the animal is able to compensate and correct the neurochemical deficit by adulthood. On the other hand, for other system (e.g. the dopaminergic in the corpus striatum), the neurochemical deficit persists into adulthood. Our recent finding that the putative endogenous convulsant and neurotoxin 3- hydroxykynurenine (3HK) is increased in vitamin B-6 restricted neonatal rat brain has important implications to the developing central nervous system. The exposure of vulnerable neurons to such an insult can produce cell degeneration whose symptoms may manifest themselves immediately after the exposure or later in life according to the level of exposure that occurred. Proposed studies are designed to assess the convulsant and neurotoxic properties of 3HK in vivo. Our proposed work is designed to continue the characterization of neurochemical changes present in vitamin B-6 restricted neonatal rat brain as well as the elucidation of underlying mechanisms which may help explain the observed neurochemical changes. Furthermore, the observation that vitamin B-6 restricted animals have deficits in motor function (e.g. ataxia, tremor, poor balance) calls for the characterization of the spontaneous motor activity of these animals. Therefore, we are proposing to quantitatively assess the motor development of vitamin B-6 restricted animals and try to correlate it with the neurochemical measurements. These studies will continue to provide new and valuable information on the role that vitamin B-6 plays in brain function and development.
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