The maturational changes in the brain and spinal cord do not linearly proceed from immature in infants to mature in adults. Dendrites dynamically extend or retract as neurotrophic factors fluctuate. In certain cases mature neurons can be seen soon after birth, and in other cases immature neurons can be identified in the aged brain. Monoamine 'neurotransmitter'; such as serotonin (5-HT), dopamine and norepinephrine appear to function as Maintenance Growth Factors since they must be present in order to produce their maturational actions. Serotonin neurons contain TRK-B receptors and are sensitive to availability of the trophic factor, BDNF. 5-HT also functions by promoting the release of the glial extension factor, S-100beta. 5-HT and S-100beta can provide maturational signals to a variety of neurons, in both cortical and subcortical areas, and appear to be involved in regulating the maturation and release of acetylcholine and dopamine. We have shown that activation of the 5-HT1A receptor is particularly effective in inducing growth of stunted neurons. The mechanism of action of the 5-HT1A receptor involves both a direct inhibition on c-AMP and pCREB formation in postsynaptic neurons and a release of S-100beta from glial cells. Both these events are capable of stabilization and elaboration of the cytoskeleton of the neuron and inhibition of apoptosis. 5-HT1A receptors have been shown to effectively reverse stunted neurons and microencephaly produced,in animal models of fetal alcohol syndrome and prenatal cocaine administration. I discuss the implications for regressive disorders such as Rett's syndrome and autism, and the feasibility of treatments with 5-HT1A agonists in children with developmental disorders. (C) 2001 Elsevier Science B.V. All rights reserved.
机构:
Stanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USAStanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USA
Kang, Augustine W.
Chi, Kevin W.
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Stanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USAStanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USA
Chi, Kevin W.
Stevenson, Terrell N.
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Stanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USA
Santa Clara Valley Med Ctr, San Jose, CA USAStanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USA
机构:
Cent Massachusetts Special Educ Collaborat, Worcester, MA 01606 USACent Massachusetts Special Educ Collaborat, Worcester, MA 01606 USA
Thompson, Valerie
Block, Martin E.
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Univ Virginia, Curry Sch Educ, Charlottesville, VA 22903 USA
Univ Virginia, Masters Program Adapted Phys Educ, Charlottesville, VA 22903 USACent Massachusetts Special Educ Collaborat, Worcester, MA 01606 USA