Toxic effects of lead on neuronal development and function.
The effects of lead on the development of the nervous system are of immediate concern to human health. While it is clear that lead can affect neuronal development at levels of exposure within the range found in the environment, the particular mechanism of the disruption is not readily ascertained. Lack of knowledge of the mechanisms of lead-induced damaged hampers its treatment and prevention. The goal of our research is to develop a model system in which the effects of lead on central nervous system development can be demonstrated. The complexity of the brain hampers such investigations because often it is not clear if apparent toxic effects represents changes secondary to somatic changes, such as endocrine or hematological defects, that could alter brain development, or even transneuronal effects caused by toxicity at a distal site that deprives a brain area of a synaptic input needed for its proper development. A related problem is the redundancy of compensatory systems in the brain. Such system may disguise the severity of the initial toxic insult and themselves can cause functional disturbances. To study neuronal development in a system that minimizes such difficulties, we have grafted discrete brain regions derived from rat fetuses into the anterior chamber of the eye of adult hosts. The brain pieces continue organotypic development of the eye, but are isolated from possible secondary changes due to alterations in the development of the endocrine and other somatic systems because the adult host has these systems already fully developed. Similarly, effects mediated by connecting brain areas are minimized since the transplant is isolated in the anterior chamber of the eye.(ABSTRACT TRUNCATED AT 250 WORDS)
Freedman
R
R
Department of Psychiatry, Denver Veterans Administration Medical Center, CO 80262.
Olson
L
L
Hoffer
B J
BJ
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000867:Anterior Chamber / Q000294:innervation; D002490:Central Nervous System / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D002531:Cerebellum / Q000637:transplantation; D004594:Electrophysiology; D007498:Iris / Q000294:innervation; D007854:Lead / Q000633:toxicity*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats
D007854:Lead