scholarly journals Effects of ACTH, dexamethasone, and adrenalectomy on 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system

2007 ◽  
Vol 196 (2) ◽  
pp. 305-311 ◽  
Author(s):  
Ping Ye ◽  
Christopher J Kenyon ◽  
Scott M MacKenzie ◽  
Katherine Nichol ◽  
Jonathan R Seckl ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adrenal Gland ◽  
Brain Regions ◽  
Dietary Sodium ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Aldosterone Synthase ◽  
The Central Nervous System ◽  
Wistar Kyoto

Using a highly sensitive quantitative RT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs, we previously demonstrated that CYP11B2 expression in the central nervous system (CNS) is subject to regulation by dietary sodium. We have now quantified the expression of these genes in the CNS of male Wistar Kyoto (WKY) rats in response to systemic ACTH infusion, dexamethasone infusion, and to adrenalectomy. CYP11B1 and CYP11B2 mRNA levels were measured in total RNA isolated from the adrenal gland and discrete brain regions using real-time quantitative RT-PCR. ACTH infusion (40 ng/day for 7 days, N=8) significantly increased CYP11B1 mRNA in the adrenal gland, hypothalamus, and cerebral cortex compared with animals infused with vehicle only. ACTH infusion decreased adrenal CYP11B2 expression but increased expression in all of the CNS regions except the cortex. Dexamethasone (10 μg/day for 7 days, N=8) reduced adrenal CYP11B1 mRNA compared with control animals but had no significant effect on either gene's expression in the CNS. Adrenalectomy (N=6 per group) significantly increased CYP11B1 expression in the hippocampus and hypothalamus and raised CYP11B2 expression in the cerebellum relative to sham-operated animals. This study confirms the transcription of CYP11B1 and CYP11B2 throughout the CNS and demonstrates that gene transcription is subject to differential regulation by ACTH and circulating corticosteroid levels.

scholarly journals Regulation of Aldosterone Synthase Gene Expression in the Rat Adrenal Gland and Central Nervous System by Sodium and Angiotensin II

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3321-3328 ◽  
Author(s):  
Ping Ye ◽  
Christopher J. Kenyon ◽  
Scott M. MacKenzie ◽  
Jonathan R. Seckl ◽  
Robert Fraser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Adrenal Gland ◽  
Brain Regions ◽  
Dietary Sodium ◽  
Mrna Levels ◽  
Aldosterone Synthase ◽  
Qrt Pcr ◽  
Wistar Kyoto

Abstract We have developed a highly sensitive QRT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs to study their expression in the rat brain in response to dietary sodium manipulation and angiotensin (Ang)II infusion. Male Wistar Kyoto rats (n = 6) were fed normal, high, or low sodium diets for 12 d or were administered AngII or vehicle for 7 d. CYP11B2 and CYP11B1 expression was measured in RNA from adrenal gland and discrete brain regions using real-time QRT-PCR. Sodium restriction increased adrenal CYP11B2 expression 57-fold from 1.0 × 105 ± 0.6 × 105 to 57 × 105 ± 22 × 105 copies/μg RNA (mean ± sem; P < 0.05);in the hippocampus, 14-fold from 5.4 × 102 ± 0.8 × 102 to 74 × 102 ± 31 × 102 copies/μg RNA (P < 0.05); and in the cerebellum, 5-fold from 1.9 × 103 ± 0.7 × 103 to 9.9 × 103 ± 3.0 × 103 copies/μg RNA (P < 0.01). CYP11B2 gene expression in the brainstem and hypothalamus was not affected. High-sodium diet reduced adrenal CYP11B2 expression to 0.19 × 105 ± 0.1 × 105 copies/μg RNA (P < 0.05) but did not affect central nervous system (CNS) expression significantly. AngII significantly increased adrenal CYP11B2 expression but did not affect CNS expression. Brain CYP11B1 mRNA levels were 10- to 1000-fold higher than CYP11B2 but were unaffected by dietary sodium or AngII. To summarize, we have identified a local CYP11B2 response to sodium depletion in the hippocampus and cerebellum. This is the first such regulation of CYP11B2 transcription to be identified in the CNS.

Low concentrations of hydrogen sulphide alter monoamine levels in the developing rat central nervous system

1992 ◽  
Vol 70 (11) ◽  
pp. 1515-1518 ◽  
Author(s):  
B. Skrajny ◽  
R. S. Hannah ◽  
S. H. Roth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Frontal Cortex ◽  
Hydrogen Sulphide ◽  
Chronic Exposure ◽  
Brain Regions ◽  
Target Organs ◽  
Low Concentrations ◽  
The Central Nervous System ◽  
Developing Rat

The central nervous system is one of the primary target organs for hydrogen sulphide (H2S) toxicity; however, there are limited data on the neurotoxic effects of low-dose chronic exposure on the developing nervous system. Levels of serotonin and norepinephrine in the developing rat cerebellum and frontal cortex were determined following chronic exposure to 20 and 75 ppm H2S during perinatal development. Both monoamines were altered in rats exposed to 75 ppm H2S compared with controls; serotonin levels were significantly increased at days 14 and 21 postnatal in both brain regions, and norepinephrine levels were significantly increased at days 7, 14, and 21 postnatal in cerebellum and at day 21 in the frontal cortex. Exposure to 20 ppm H2S significantly increased the levels of serotonin in the frontal cortex at day 21, whereas levels of norepinephrine were significantly reduced in the frontal cortex at days 14 and 21, and at day 14 in the cerebellum.Key words: hydrogen sulphide, monoamines, serotonin, norepinephrine, neurotoxicity.

scholarly journals Neuropathological Findings in a Case of IFIH1-Related Aicardi–Goutières Syndrome

2019 ◽  
Vol 22 (6) ◽  
pp. 566-570
Author(s):  
Ahmed Gilani ◽  
Laura A Adang ◽  
Adeline Vanderver ◽  
Abigail Collins ◽  
BK Kleinschmidt-DeMasters
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Atrophy ◽  
Cardiopulmonary Arrest ◽  
Brain Regions ◽  
Variable Degree ◽  
Expression Data ◽  
Ultrastructural Examination ◽  
The Central Nervous System ◽  
Gross Examination

Aicardi–Goutières syndrome (AGS) is a rare syndrome characterized by calcification, diffuse demyelination, and variable degree of brain atrophy. The syndrome is genetically heterogeneous with mutations in 7 genes, including TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1 (interferon-induced helicase c domain-containing protein 1) associated with the syndrome, so far. These mutations lead to the overproduction of α-interferon within the central nervous system. Mutations in IFIH1 have been recently described in a subset of AGS, with only 1 previous report of neuropathological findings. We report neuropathological findings in a second case of AGS with a known mutation in IFIH1 gene. The patient is a 16-year-old adolescent boy with early-onset symptoms that progressed to profound loss of cognitive and motor functions. The patient experienced sudden cardiopulmonary arrest at the age of 16 years. At autopsy, the cause of death was determined to be pulmonary thromboembolism. Neuropathological examination revealed microcephaly (brain weight: 916 g) with relatively mild brain atrophy on gross examination. Microscopic examination revealed multifocal calcifications limited to small to medium central nervous system arteries (no evidence of calcification in other organs), involving bilateral cerebral cortex, basal ganglia, thalamus, and cerebellum. Ultrastructural examination showed Calcospherules limited to the vessel walls and the perivasulcar area without evidence of neuronal ferrugination or tubuloreticular bodies. The extent of calcifications was variable across different brain regions, resembling findings in previously reported cases and correlated with the extent of IFIH1 protein expression (data derived from Allen Brain Institute). AGS is a rare cause of brain calcifications that can closely mimic congenital and neonatal infections such as Rubella and similar infections.

scholarly journals 11beta-hydroxylase and aldosterone synthase expression in fetal rat hippocampal neurons

2002 ◽  
Vol 29 (3) ◽  
pp. 319-325 ◽  
Author(s):  
SM MacKenzie ◽  
M Lai ◽  
CJ Clark ◽  
R Fraser ◽  
CE Gomez-Sanchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Local System ◽  
Model System ◽  
Biochemical Reactions ◽  
Aldosterone Synthase ◽  
Fetal Rat ◽  
The Central Nervous System

The central nervous system produces many of the enzymes responsible for corticosteroid synthesis. A model system to study the regulation of this local system would be valuable. Previously, we have shown that primary cultures of hippocampal neurons isolated from the fetal rat can perform the biochemical reactions associated with the enzymes 11beta-hydroxylase and aldosterone synthase. Here, we demonstrate directly that these enzymes are present within primary cultures of fetal rat hippocampal neurons.

Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats

1999 ◽  
Vol 96 (3) ◽  
pp. 307-312 ◽  
Author(s):  
Simon DRYDEN ◽  
Peter KING ◽  
Lucy PICKAVANCE ◽  
Patrick DOYLE ◽  
Gareth WILLIAMS
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Leptin Receptor ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Zucker Rat ◽  
Direct Effects ◽  
The Central Nervous System

Leptin inhibits feeding and decreases body weight. It may act partly by inhibiting hypothalamic neurons that express neuropeptide Y, a powerful inducer of feeding and obesity. These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. We compared the effects of three doses of leptin given intracerebroventricularly and three doses of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. In lean rats, 4-h food intake was reduced in a dose-related fashion (P< 0.01) by all intracerebroventricular leptin doses and by intraperitoneal doses of 300 and 600 μg/kg. Neuropeptide Y mRNA levels were reduced by 28% and 21% after the highest intracerebroventricular and intraperitoneal doses respectively (P< 0.01 for both). In fatty rats, only the highest intracerebroventricular leptin dose reduced food intake (by 22%; P< 0.01). Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P< 0.01) after the highest intracerebroventricular leptin dose. Intraperitoneal injection had no effect on food intake and neuropeptide Y mRNA. The fa/fa Zucker rat is therefore less sensitive to leptin given intracerebroventricularly and particularly intraperitoneally, suggesting that the fa mutation interferes both with leptin's direct effects on neurons and its transport into the central nervous system. Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons.

scholarly journals Spread and Replication of and Immune Response to γ134.5-Negative Herpes Simplex Virus Type 1 Vectors in BALB/c Mice

2004 ◽  
Vol 78 (23) ◽  
pp. 13139-13152 ◽  
Author(s):  
Eeva K. Broberg ◽  
Jutta Peltoniemi ◽  
Michaela Nygårdas ◽  
Tero Vahlberg ◽  
Matias Röyttä ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Herpes Simplex ◽  
Trigeminal Ganglia ◽  
Rt Pcr ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

ABSTRACT We have previously shown that intracranial infection of herpes simplex virus type 1 (HSV-1) vector R8306 expressing interleukin-4 (IL-4) can abolish symptoms of experimental autoimmune encephalomyelitis, which is used as a model for human multiple sclerosis (Broberg et al., Gene Ther. 8:769-777, 2001). The aim of the current study was to search for means other than intracranial injection to deliver HSV-derived vectors to the central nervous system of mice. We also aimed to study the replication efficiency of these vectors in nervous system tissues and to elucidate the effects of the viruses on the immune response. We studied the spread and replication of the following viruses with deletions in neurovirulence gene γ134.5: R3616, R849 (lacZ transgene), R3659 (alpha-tk), R8306 (murine IL-4 transgene), and R8308 (murine IL-10 transgene). The samples were taken from trigeminal ganglia and brains of BALB/c mice after corneal, intralabial, and intranasal infection, and the viral load was examined by viral culture, HSV DNA PCR, and VP16 reverse transcription (RT)-PCR. The results show that (i) intranasal infection was the most efficient means of spread to the central nervous system (CNS) besides intracranial injection; (ii) the viruses did not grow in the culture from the brain samples, but the viral DNA persisted even until day 21 postinfection; (iii) viral replication, as observed by VP16 mRNA RT-PCR, occurred mainly on days 4 and 7 postinfection in trigeminal ganglia and to a low extent in brain; (iv) R3659, R8306, and R8308 showed reactivation from the trigeminal ganglia in explant cultures; (v) in the brain, the vectors spread to the midbrain more efficiently than to other brain areas; and (vi) the deletions in the R3659 genome significantly limited the ability of this virus to replicate in the nervous system. The immunological studies show that (i) the only recombinant to induce IL-4 mRNA expression in the brain was R8306, the gamma interferon response was very low in the brain for R3659 and R8306, and the IL-23p19 response to R8306 decreased by day 21 postinfection, unlike for the other viruses; (ii) Δγ134.5 HSV vectors modulated the subsets of the splenocytes differently depending on the transgene; (iii) R3659 infection of the nervous system induces expression and production of cytokines from the stimulated splenocytes; and (iv) HSV vectors expressing IL-4 or IL-10 induce expression and production of both of the Th2-type cytokines from splenocytes. We conclude that the intranasal route of infection is a possible means of delivery of Δγ134.5 HSV vectors to the CNS in addition to intracranial infection, although replication in the CNS remains minimal. The DNA of the HSV vectors is able to reside in the brain for at least 3 weeks. The features of the immune response to the vectors must be considered and may be exploited in gene therapy experiments with these vectors.

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