Molecular and pharmacological analysis of cyclic nucleotide-gated channel function in the central nervous system.

Most functional studies of cyclic nucleotide-gated (CNG) channels have been confined to photoreceptors and olfactory epithelium, in which CNG channels are abundant and easy to study. The widespread distribution of CNG channels in tissues throughout the body has only recently been recognized and the functions of this channel family in many of these tissues remain largely unknown. The molecular biological and pharmacological properties of the CNG channel family are summarized in order to put in context studies aimed at probing CNG channel functions in these tissues using pharmacological and genetic methods. Compounds have now been identified that are useful in distinguishing CNG channel activated pathways from cAMP/cGMP dependent-protein kinases or other pathways. The ways in which these interact with CNG channels are understood and this knowledge is leading to the identification of more potent and more specific CNG channel subtype-specific agonists or antagonists. Recent molecular and genetic analyses have identified novel roles of CNG channels in neuronal development and plasticity in both invertebrates and vertebrates. Targeting CNG channels via specific drugs and genetic manipulation (such as knockout mice) will permit better understanding of the role of CNG channels in both basic and higher orders of brain function.

Fat-gram counting and food-record rating are equally effective for evaluating food records in reduced-fat diets.

OBJECTIVE: To compare rates of adherence to low-fat diets using food-record rating and fat-gram counting, to evaluate dietary adherence using the fat-gram counting method, and to assess correlations between food-record rating and fat-gram counting. DESIGN: A diet monitoring and observation study was conducted to compare the effectiveness of food-record rating and fat-gram counting to evaluate dietary adherence. Subjects were randomly assigned to the food-record rating group of the fat-gram counting group. Each participant was asked to complete four 3-day food records. Food records were evaluated by food-record rating for one group and by fat-gram counting for the other. Each record was then scored using the alternate system. For a subset, manually calculated fat-gram values were compared for accuracy with values from the Nutrient Data Systems database. STATISTICAL ANALYSES PERFORMED: Mantel-Haenszel chi 2, regression, and K analyses were used to evaluate adherence rates and within-subject agreement between fat-gram counting and food-record rating. SUBJECTS/SETTING: Seventy-eight participants were recruited from a lipid-lowering research trial conducted in Houston, Tex. RESULTS: Strong correlations were found between fat-gram values calculated manually and those calculated using the Nutrient Data Systems. No significant differences in adherence rates were found between the food-record rating and fat-gram counting groups. CONCLUSIONS: Fat-gram counting is at least as effective as food-record rating in monitoring dietary fat content. Dietitians can use it as an alternative dietary fat-monitoring procedure for clinical practice and research.

Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid.

The mechanisms of delayed onset and cell death in Huntington's disease (HD) are unknown. One possibility is that a genetic defect in energy metabolism may result in slow excitotoxic neuronal death. Therefore, we examined the effects of age on striatal lesions produced by local administration of the mitochondrial toxin 3-nitropropionic acid in rats. In vivo chemical shift magnetic resonance imaging showed marked increases in striatal lactate concentrations that significantly correlated with increasing age. Histologic and neurochemical studies showed a striking age dependence of the lesions, with 4- and 12-month-old animals being much more susceptible than 1-month-old animals. Continuous systemic administration of low doses of 3-nitropropionic acid for 1 month resulted in striatal lesions showing growth-related changes in dendrites of striatal spiny neurons using the Golgi technique. These results show that a known mitochondrial toxin can produce selective axon-sparing striatal lesions showing both the age dependence and striatal spiny neuron dendritic changes that characterize HD.