Takeo Deguchi

Coordinate expression of vesicular acetylcholine transporter and choline acetyltransferase in sympathetic superior cervical neurones

&NA; The neurotransmitter acetylcholine is synthesized by choline acetyltransferase (ChAT) and transported into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). Recently it has been reported that the entire coding region of VAChT mRNA is located in the first intron of the ChAT gene. In this study, ChAT and VAChT mRNAs were analysed in cultured sympathetic neurones. Cholinergic differentiation factor/leukaemia inhibitory factor and ciliary neurotrophic factor induced strong expression of ChAT and VAChT mRNAs in parallel. RT‐PCR analysis of ChAT mRNAs revealed that five types of ChAT transcripts which differed in the 5′ non coding regions were increased. RT‐PCR analysis of VAChT mRNA indicated that the cytokines induced only VAChT mRNA species which did not contain the R‐exon, and not those containing the R‐exon. The results indicate that ChAT and VAChT expressions are coordinately but differentially regulated in cultured sympathetic neurones.

BIOSYNTHESIS OF SEROTONIN IN RAPHÉ NUCLEI OF RAT BRAIN: EFFECT OF p‐CHLOROPHENYLALANINE1

The activity of tryptophan hydroxylase (EC 1.99.1.4) in the region of the raphé nuclei of rat brain was higher than that of any other brain area. The content of serotonin and the rate of serotonin synthesis were also highest in the raphé nuclei. Following the administration of p‐chlorophenylalanine the injection of tryptophan and pargyline increased the content of serotonin in the region of the raphé nuclei of rat brain. The results suggest that the raphé nuclei retained the capacity to hydroxyl‐late tryptophan to some extent after the injection of p‐chlorophenylalanine.

Genetic differences in mechanisms involving neuroregulators

Publisher Summary This chapter discusses genetic differences in mechanisms involving neuroregulators. The potential role of genetic factors becomes of great importance in terms of a number of theories of the illness. The possibility of genetic variation in catecholamine synthesizing activity is suggested by several lines of evidence. In animals, strain and subline differences have been reported in the amounts of biogenic amines in brain regions of mice and rats and in the utilization and uptake of cardiac norepinephrine in mice. In humans, a variety of forms of pheochromocytoma have been shown to be associated with familial factors. There are known genetic variations in adrenocortical and adrenomedullary structure. Genetic variations in steroid hormones produced by the adrenal cortex and in thyroid hormone have been associated with behavioral changes, and further e search for genetic variation in the enzymes involved in catecholamine biosynthesis would be fruitful. The use of inbred mouse strains is particularly advantageous in studies of genetic variation and provides a powerful tool for subsequent behavioral and genetic analysis.

Sleep and serotonin in two strains of Mus musculus.

Abstract Two strains of Mus musculus , C57BL/10J and BALB/CJ, were studied in an attempt to check for any naturally occurring correlation between sleep and brain serotonin. The C57BL/10J compared with the BALB/CJ had more slow wave sleep throughout the day and particularly during hours of darkness. During peak sleep periods, C57BL/10J also had more REM sleep. At three different times of the day (1200, 1600, and 0400 hr) neurochemical assays were done on brain stem and cerebral cortex for tryptophan and serotonin levels and for tryptophan hydroxylase activity. An inspection of the ordering of means for strains suggested that the greater amount of slow wave sleep for C57BL/10J was paralleled by higher brain stem and cortex tryptophan levels, higher cortex tryptophan hydroxylase activity, and higher cortex serotonin levels. An inspection of temporal trends across strain and time of day suggested that slow wave sleep may vary negatively with brain stem tryptophan hydroxylase activity, brain stem serotonin level, and cortex tryptophan level. While no simple sleep-serotonin relationship obtained, because of such trends the data were interpreted as being generally consistent with the hypothesis of an active serotonergic sleep inducing mechanism in brain.

Enzyme activity in sleep and sleep deprivation

Liver tyrosine transaminase activity is low during the day when the rats are mostly asleep and high during the night when they are awake. When wakefulness was imposed for 8 hr during daylight on the day of the experiment and the rats were allowed to sleep for the following 3 hr during darkness, the tyrosine transaminase activity became high during the day and low at night. That this reversal in enzyme activity is not mediated by the pituitary-adrenal axis is demonstrated by the fact that in adrenalectomized rats tyrosine transaminase activity increased during the day in the sleep deprived rats. However, in these rats the enzyme activity did not become low in the sleep-deprived-sleeping condition. Changes in tryptophan pyrrolase activity during sleep deprivation were demonstrated to be mediated by the pituitary-adrenal axis.

GENETIC DIFFERENCES IN MECHANISMS INVOLVING NEUROREGULATORS

Publisher Summary This chapter discusses genetic differences in mechanisms involving neuroregulators. The potential role of genetic factors becomes of great importance in terms of a number of theories of the illness. The possibility of genetic variation in catecholamine synthesizing activity is suggested by several lines of evidence. In animals, strain and subline differences have been reported in the amounts of biogenic amines in brain regions of mice and rats and in the utilization and uptake of cardiac norepinephrine in mice. In humans, a variety of forms of pheochromocytoma have been shown to be associated with familial factors. There are known genetic variations in adrenocortical and adrenomedullary structure. Genetic variations in steroid hormones produced by the adrenal cortex and in thyroid hormone have been associated with behavioral changes, and further e search for genetic variation in the enzymes involved in catecholamine biosynthesis would be fruitful. The use of inbred mouse strains is particularly advantageous in studies of genetic variation and provides a powerful tool for subsequent behavioral and genetic analysis.