A biogenic amine-synapse mechanism for mental retardation and developmental disabilities.
Recent studies have demonstrated that biogenic amines have a function of facilitating formation and maintenance of synapses in diverse regions of the central nervous system in developing and adult animals. The normal number of synapses maintained by biogenic amines are crucial to acquire learning and memory. The level of biogenic amines was reported to decrease in the brain by several neurodevelopmental disorders associated with mental retardation and developmental disabilities such as Rett syndrome, autism and Down syndrome. Taken into consideration this fact together with the function of biogenic amines for synapses, the density of synapses appears to decrease considerably in the brains of patients suffered from the neurodevelopmental disorders. The synaptic overproduction during the critical period of development especially 1 year after birth has been considered as a background mechanism to provide plasticity for the developing brain. Synaptic overproduction does not appear to occur in the brains of patients suffered from the neurodevelopmental disorders, which they are observed mental retardation occurring in the first 1 year after birth. Along with the neurodevelopmental disorders, environmental factors (stress, drugs and nutrition) during pre- and post-natal critical developmental periods are known to change levels of biogenic amines in the brain. In fact, maternal stress has been shown to decrease the levels of serotonin and the density of synapses in the hippocampus of the offspring, and they showed developmental disabilities in the spatial learning and memory. A cascade appears to exist from either the child neurological disorders or the environmental factors to mental retardation and developmental disabilities by decreases in the levels of biogenic amines and synaptic density.
Okado
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Neurobiology Laboratory, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8577, Tsukuba, Japan. nokado@md.tsukuba.ac.jp
Narita
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M
Narita
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N
D000818:Animals; D015306:Biogenic Monoamines / Q000172:deficiency*; D002490:Central Nervous System / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009421:Nervous System Malformations / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
D015306:Biogenic Monoamines; D012701:Serotonin