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Apoptosis is a morphologically defined form of programmed cell death seen in a variety of circumstances, including immune cell selection, carcinogenesis and development. Apoptosis has very recently been seen after ischemic or traumatic injury to the central nervous system (CNS), suggesting that active cell death as well as passive necrosis may mediate(More)
Presynaptic histamine H(3) receptors (H(3)R) regulate neurotransmitter release in the central nervous system, suggesting an important role for H(3) ligands in human diseases such as cognitive disorders, sleep disturbances, epilepsy, or obesity. Drug development for many of these human diseases relies upon rodent-based models. Although there is significant(More)
Glucocorticoid hormones, acting through two types of intracellular receptors to modulate gene activity, have diverse behavioral, neurochemical and neurodegenerative effects in hippocampus. We have previously cloned hippocampal mRNAs that respond to the endogenous glucocorticoid, corticosterone (CORT): glycerol phosphate dehydrogenase (EC 1.1.1.8; GPDH), an(More)
Twenty-five years ago, glycerol phosphate dehydrogenase (GPDH, EC 1.1.1.8) was described as a hormonally dependent enzyme in the brain, and since then has been characterized for its developmental regulation and as a marker for oligodendrocytes. These studies describe the cloning of GPDH mRNA from adult rat hippocampus and its characterization as an in vivo(More)
The nucleotide sequence of the human dihydrofolic acid reductase (DHFR) reading frame has been derived from the analysis of human DHFR cDNA. This sequence and the corresponding amino acid sequence have been compared with those available for the enzyme and its coding segment from other organisms. There is an 89% nucleotide sequence homology between the human(More)
A hippocampal poly(A) RNA, pADHC-9, was cloned by differential screening of a human hippocampal cDNA library. By RNA blot analysis, pADHC-9 was elevated 2-fold in Alzheimer's disease hippocampus. In situ analyses identified pADHC-9 expression in pyramidal and non-pyramidal cells of the hippocampus and entorhinal cortex. Nucleotide sequence analysis(More)
Glucocorticoid receptor (GR) ontogeny and distribution in postnatal rat brain have been demonstrated, but onset and distribution of GR gene expression during fetal life has not been reported. This study focuses on the distribution of GR-mRNA in the fetal and postnatal rat forebrain, with emphasis on hypothalamic and limbic structures. Time pregnant rats(More)
RNA coding for a 50 kDa polypeptide decreased by 50% in 5 brain regions after corticosterone (CORT) treatment (40 mg/kg for 3 days). By hybrid selection and in vitro translation, the 50 kDa polypeptide is identified as glial fibrillary acidic protein (GFAP). Hippocampal GFAP mRNA (2.9 kb) decreases in a dose-dependent manner in response to CORT by RNA blot(More)
Glucocorticoids (GCs) are highly pathogenic if secreted in excess. Recent work shows that such deleterious consequences include damage to the hippocampus, a principal neural target site for GCs. Excessive chronic exposure to GCs accelerates senescent hippocampal neuron loss, while the presence of GCs at the time of neurological insults, such as seizure or(More)
We describe the usability of human pooled hepatocytes for non-CYP metabolism evaluation and an in vivo-in vitro correlation analysis for aldehyde oxidase (AO) substrate compounds using pooled hepatocytes. By comparing intrinsic clearance values of 18 compounds primarily metabolized by AO, UDP-glucuronosyltransferase, carbonyl/aldo-keto reductase,(More)