Advances in Experimental Medicine and Biology, 1998
The development, function and maintenance of the central nervous system (CNS) tissue are regulate... more The development, function and maintenance of the central nervous system (CNS) tissue are regulated in a timed sequence of inductions by growth factors (GF) and neuroactive amino acids (NAA)16. Taurine in particular has been identified as a “balancing factor” in the glutamate system to modulate and stabilize calcium homeostasis or enantiostasis and thus calcium-dependent cellular functions (for reviews22,44,50,48).
Our previous study showed an improvement in locomotor deficits after voluntary lifelong running i... more Our previous study showed an improvement in locomotor deficits after voluntary lifelong running in Ts65Dn mice, an animal model for Down syndrome (DS). In the present study, we employed mouse microarrays printed with 55,681 probes in an attempt to identify molecular changes in the cerebellar transcriptome that might contribute to the observed behavioral benefits of voluntary long-term running in Ts65Dn mice. Euploid mice were processed in parallel for comparative purposes in some analyses. We found that running significantly changed the expression of 4,315 genes in the cerebellum of Ts65Dn mice, over five times more than in euploid animals, up-regulating 1,991 and down-regulating 2,324 genes. Functional analysis of these genes revealed a significant enrichment of 92 terms in the biological process category, including regulation of biosynthesis and metabolism, protein modification, phosphate metabolism, synaptic transmission, development, regulation of cell death/apoptosis, protein t...
Publisher Summary This chapter discusses approach for discovering conditions under which normal f... more Publisher Summary This chapter discusses approach for discovering conditions under which normal fetal tissue transplanted into infant brains could ameliorate impaired function resulting from congenital brain defects. The approach is unique in 2 respects: (1) by adding new rather than replacing lost tissue, it improves the function of the host brain beyond its intrinsic capacity and (2) functional effects are assessed at maturity and in old age, even though transplants are sustained in infancy. The effect of transplants on some of the impaired behaviors is described in the chapter. In the approach described in the chapter, although the transplant was structurally well integrated into the host brain, its presence reduced neither the hyperactivity of micrencephalic rats in an open field nor the deficit they display in learning a multiple choice water maze. Both tests were done at 2 months and one year after transplantation. Electrophysiological recordings of electroencephalography and visual evoked potentials (VEP) obtained from young adult transplant-bearing micrencephalic rats have been more encouraging. Salutary transplant effects were also observed with two different behavioral tests given at older ages, a visual pattern discrimination test and spatial navigation.
Application of Basic Neuroscience to Child Psychiatry, 1990
Down’s syndrome (DS), or trisomy 21, is a major known cause of mental retardation, occurring in 1... more Down’s syndrome (DS), or trisomy 21, is a major known cause of mental retardation, occurring in 1 of every 1000 live births.1 Alzheimer’s disease (AD) is a progressive dementing disorder, with characteristic brain pathology, that affects about 10% of people over 65 years of age.2 3 The presence of Alzheimer-type pathology in the brains of almost all people 35 years and older with DS has been the cornerstone for the widely held view that people with DS will develop AD not only at a much younger age, but also in much larger numbers than will people without DS.4-7 Because of this relationship between DS and AD, it has been widely assumed that knowledge about almost any aspect of one of these conditions will illuminate the other.8-11 For example, the similarity of the morphological and neurochemical abnormalities in AD and DS has led to the proposition that aging DS brains may serve as a model for the pathogenesis of brain abnormalities in AD.12 13 In addition, since DS is a genetic disorder with many features of premature aging,14 it has been expected that the study of DS will contribute important information about the role of genetics and aging in the etiology of AD.15-19
Advances in Experimental Medicine and Biology, 1998
The development, function and maintenance of the central nervous system (CNS) tissue are regulate... more The development, function and maintenance of the central nervous system (CNS) tissue are regulated in a timed sequence of inductions by growth factors (GF) and neuroactive amino acids (NAA)16. Taurine in particular has been identified as a “balancing factor” in the glutamate system to modulate and stabilize calcium homeostasis or enantiostasis and thus calcium-dependent cellular functions (for reviews22,44,50,48).
Our previous study showed an improvement in locomotor deficits after voluntary lifelong running i... more Our previous study showed an improvement in locomotor deficits after voluntary lifelong running in Ts65Dn mice, an animal model for Down syndrome (DS). In the present study, we employed mouse microarrays printed with 55,681 probes in an attempt to identify molecular changes in the cerebellar transcriptome that might contribute to the observed behavioral benefits of voluntary long-term running in Ts65Dn mice. Euploid mice were processed in parallel for comparative purposes in some analyses. We found that running significantly changed the expression of 4,315 genes in the cerebellum of Ts65Dn mice, over five times more than in euploid animals, up-regulating 1,991 and down-regulating 2,324 genes. Functional analysis of these genes revealed a significant enrichment of 92 terms in the biological process category, including regulation of biosynthesis and metabolism, protein modification, phosphate metabolism, synaptic transmission, development, regulation of cell death/apoptosis, protein t...
Publisher Summary This chapter discusses approach for discovering conditions under which normal f... more Publisher Summary This chapter discusses approach for discovering conditions under which normal fetal tissue transplanted into infant brains could ameliorate impaired function resulting from congenital brain defects. The approach is unique in 2 respects: (1) by adding new rather than replacing lost tissue, it improves the function of the host brain beyond its intrinsic capacity and (2) functional effects are assessed at maturity and in old age, even though transplants are sustained in infancy. The effect of transplants on some of the impaired behaviors is described in the chapter. In the approach described in the chapter, although the transplant was structurally well integrated into the host brain, its presence reduced neither the hyperactivity of micrencephalic rats in an open field nor the deficit they display in learning a multiple choice water maze. Both tests were done at 2 months and one year after transplantation. Electrophysiological recordings of electroencephalography and visual evoked potentials (VEP) obtained from young adult transplant-bearing micrencephalic rats have been more encouraging. Salutary transplant effects were also observed with two different behavioral tests given at older ages, a visual pattern discrimination test and spatial navigation.
Application of Basic Neuroscience to Child Psychiatry, 1990
Down’s syndrome (DS), or trisomy 21, is a major known cause of mental retardation, occurring in 1... more Down’s syndrome (DS), or trisomy 21, is a major known cause of mental retardation, occurring in 1 of every 1000 live births.1 Alzheimer’s disease (AD) is a progressive dementing disorder, with characteristic brain pathology, that affects about 10% of people over 65 years of age.2 3 The presence of Alzheimer-type pathology in the brains of almost all people 35 years and older with DS has been the cornerstone for the widely held view that people with DS will develop AD not only at a much younger age, but also in much larger numbers than will people without DS.4-7 Because of this relationship between DS and AD, it has been widely assumed that knowledge about almost any aspect of one of these conditions will illuminate the other.8-11 For example, the similarity of the morphological and neurochemical abnormalities in AD and DS has led to the proposition that aging DS brains may serve as a model for the pathogenesis of brain abnormalities in AD.12 13 In addition, since DS is a genetic disorder with many features of premature aging,14 it has been expected that the study of DS will contribute important information about the role of genetics and aging in the etiology of AD.15-19
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