American Journal of Physiology. Endocrinology and Metabolism
Xenobiotic metabolism has been proposed to play a role in modulating the rate of aging. Xenobiotic metabolizing enzymes (XME) are expressed at higher levels in calorically restricted mice (CR) and in GH/IGF-I-deficient, long-lived mutant mice. In this study, we show that many phase I XME genes are similarly upregulated in additional long-lived mouse models, including "crowded litter" (CL) mice, whose lifespan has been increased by food restriction limited to the first 3 wk of life, and in mice treated with rapamycin.
Increasing evidence suggests that epigenetic dysfunction may account for the alteration of gene transcription present in neuropsychiatric disorders such as schizophrenia (SZ), bipolar disorder (BP) and autism.
The epigenetic dysregulation of the brain genome associated with the clinical manifestations of schizophrenia (SZ) includes altered DNA promoter methylation of several candidate genes. We and others have reported that two enzymes that belong to the DNA-methylation/demethylation network pathways-DNMT1 (DNA-methyltransferase) and ten-eleven translocator-1(TET1) methylcytosine deoxygenase are abnormally increased in corticolimbic structures of SZ postmortem brain.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by symptoms related to altered social interactions/communication and restricted and repetitive behaviors. In addition to genetic risk, epigenetic mechanisms (which include DNA methylation/demethylation) are thought to be important in the etiopathogenesis of ASD.
The Journal of Pharmacology and Experimental Therapeutics
The relationship between circadian rhythms in the pharmacological actions of meperidine and hexobarbital and similar rhythms in the hepatic metabolism of these drugs was examined in mice under a variety of environmental alterations to determine whether such rhythms may be causally related. The rate of metabolism of p-nitroanisole and hexobarbital by hepatic 9000 X g supernatant fractions was found to be higher at 2400 hours (middark phase) compared to 1200 hours (midlight phase).
The duration of hexobarbital hypnosis was determined for individual male CFN rats at three month intervals over their total adult lifespan. The mean duration of hexobarbital hypnosis for the cohort linearly with advancing age. However, the sleeptimes for individual rats fell into one of four categories (gradual increase, terminal step increase, no change, or not possible to assign) when assigned as a function of duration of response to the barbiturate over the lifespan of the animals.
Research Communications in Chemical Pathology and Pharmacology
Experiments were conducted to examine the effect of manganese on drug response and metabolism in male and female rats. Three days after administration of manganese chloride (5 mg Mn/kg, ip), the duration of hexobarbital hypnosis was prolonged in male but not in female rats. Hepatic microsomal metabolism of aniline, ethylmorphine, and hexobarbital was significantly inhibited in male rats. Metabolism of aniline and ethylmorphine was also inhibited in female rats but to a lesser extent than in males. Hexobarbital metabolism was not inhibited in female rats.
Fundamental and Applied Toxicology: Official Journal of the Society of Toxicology
Experiments were conducted to examine the effect of manganese on the hepatic mixed function oxidase system in the rat. Acute treatment with manganese chloride (1-10 mg Mn/kg, ip) produced a significant prolongation of hexobarbital hypnosis in male rats on Days 2 and 3 following metal administration. The threshold dose of manganese to produce this alteration in response was 5 mg Mn/kg and the altered response returned to control values by Day 5.