2 -Deoxy – d-glucose at chronic low dose acts as a caloric restriction mimetic through a mitohormetic induction of ROS in the brain of accelerated senescence model of rat

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

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Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

Journal of Molecular Biology Research ◽

10.5539/jmbr.v7n1p171 ◽

2017 ◽

Vol 7 (1) ◽

pp. 171

Author(s):

Hamid Reza Adeli Bhroz ◽

Kazem Parivar ◽

Iraj Amiri ◽

Nasim Hayati Roodbari

Keyword(s):

Dose Group ◽

Low Dose ◽

Pure Water ◽

Intervention Group ◽

Control Group ◽

High Dose ◽

Endocrine Glands ◽

Blood Samples ◽

High Doses ◽

The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

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The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

International Journal of Endocrinology ◽

10.1155/2015/245459 ◽

2015 ◽

Vol 2015 ◽

pp. 1-17 ◽

Cited By ~ 33

Author(s):

Kira V. Derkach ◽

Vera M. Bondareva ◽

Oxana V. Chistyakova ◽

Lev M. Berstein ◽

Alexander O. Shpakov

Keyword(s):

Type 2 Diabetes ◽

High Fat Diet ◽

Low Dose ◽

Diabetic Rats ◽

Brain Serotonin ◽

Serotonin Level ◽

High Fat ◽

Brain Serotonin Level ◽

The Brain

In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation byβ-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.

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Effect of low dose exposure to the herbicide atrazine and its metabolite on cytochrome P450 aromatase and steroidogenic factor-1 mRNA levels in the brain of premetamorphic bullfrog tadpoles (Rana catesbeiana)

Aquatic Toxicology ◽

10.1016/j.aquatox.2010.12.019 ◽

2011 ◽

Vol 102 (1-2) ◽

pp. 31-38 ◽

Cited By ~ 20

Author(s):

Mark P. Gunderson ◽

Nik Veldhoen ◽

Rachel C. Skirrow ◽

Magnus K. Macnab ◽

Wei Ding ◽

...

Keyword(s):

Cytochrome P450 ◽

Low Dose ◽

Rana Catesbeiana ◽

Mrna Levels ◽

Steroidogenic Factor 1 ◽

P450 Aromatase ◽

Cytochrome P450 Aromatase ◽

Herbicide Atrazine ◽

The Brain

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CD8+ T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

Journal of Virology ◽

10.1128/jvi.77.24.13323-13334.2003 ◽

2003 ◽

Vol 77 (24) ◽

pp. 13323-13334 ◽

Cited By ~ 226

Author(s):

Yang Wang ◽

Mario Lobigs ◽

Eva Lee ◽

Arno Müllbacher

Keyword(s):

T Cells ◽

Dose Group ◽

Low Dose ◽

Neuronal Degeneration ◽

High Dose ◽

West Nile ◽

Activation Markers ◽

High Doses ◽

The Brain ◽

Deficient Mice

ABSTRACT C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (108 PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (103 PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8+, but not CD4+, T cells. CD8+ T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8+ T-cell-deficient mice infected with 103 PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8+ T cells are involved in both recovery and immunopathology in WNV infection.

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Correction: A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

PLoS ONE ◽

10.1371/annotation/7d56e94e-3582-413d-b987-fccd0da79081 ◽

2008 ◽

Vol 3 (6) ◽

Author(s):

Jamie L. Barger ◽

Tsuyoshi Kayo ◽

James M. Vann ◽

Edward B. Arias ◽

Jelai Wang ◽

...

Keyword(s):

Caloric Restriction ◽

Low Dose

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Efficacy of Low-dose Dextromethorphan in the Treatment of Nonketotic Hyperglycinemia

PEDIATRICS ◽

10.1542/peds.97.6.924 ◽

1996 ◽

Vol 97 (6) ◽

pp. 924-926

Author(s):

Ramin Alemzadeh ◽

Karsten Gammeltoft ◽

Karla Matteson

Keyword(s):

Sodium Benzoate ◽

Low Dose ◽

Epileptiform Activity ◽

Therapeutic Effects ◽

Psychomotor Delay ◽

Aspartate Receptor ◽

Nonketotic Hyperglycinemia ◽

Electroencephalographic Activity ◽

The Brain ◽

Stimulation Of

Nonketotic hyperglycinemia (NKH) is an inborn error of glycine degradation causing muscular hypotonia, seizures, apnea, and lethargy; it has a poor prognosis. Accumulation of glycine in the brain is thought to cause excessive stimulation of the N-methyl-D-aspartate receptor. Dextromethorphan (DM), an N-methyl-D-aspartate receptor antagonist, in doses of 5 to 35 mg/kg per day has been shown to have beneficial therapeutic effects in some patients with NKH. We report the case of a 1-year-old infant with NKH, seizure disorder, and psychomotor delay who was clinically seizure free during treatment with sodium benzoate, arginine, benzodiazepam, and phenobarbital. Although sodium benzoate normalized serum glycine levels (103 to 125 µmol/L), cerebrospinal fluid glycine levels remained elevated (42 to 47 µmol/L), with epileptiform activity on electroencephalography. The addition of low-dose DM (0.25 mg/kg per day) to the treatment led to improvement of electroencephalographic activity, resolution of nystagmus with increased eye contact, and modest progression of developmental milestones. These data suggest that DM at doses significantly lower than previously reported may be beneficial in some patients with NKH. Treatment with low-dose DM needs further evaluation.

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Abstract P331: Angiotensin-salt Hypertension Requires Ouabain-sensitive Na + Pumps

Hypertension ◽

10.1161/hyp.70.suppl_1.p331 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Ling Chen ◽

Jerry B Lingrel ◽

John M Hamlyn ◽

Mordecai P Blaustein

Keyword(s):

Low Dose ◽

High Dose ◽

Ang Ii ◽

Wild Type ◽

Dietary Salt ◽

Endogenous Ligand ◽

Ouabain Binding ◽

Fab Fragments ◽

Salt Hypertension ◽

The Brain

Dietary salt is a major factor in the pathogenesis of essential hypertension (EH), but the underlying links are unresolved. Animal models indicate that angiotensin (Ang) II and high dietary salt (HS) are convergent signals that act via the brain to elevate blood pressure (BP). Low-dose sc Ang II+HS is a common model for EH. We tested the Na + pump ouabain binding site’s role in this model because it is crucial in some other hypertension models (e.g., ACTH and Nedd4-2-knockout +HS). Mice that express Na + pumps with a mutant, ouabain-resistant α2 catalytic subunit (α2 R/R ; cation transport is normal), and wild type (WT), ouabain sensitive controls (α2 S/S ) were studied. [80-90% of rodent artery myocyte Na + pumps are ouabain-resistant (α1 R/R ); only 10-20% are α2.] BP was measured by telemetry. First, 3 basal 24 hr BPs were recorded. Osmotic 4-week minipumps were then implanted sc in all mice to deliver vehicle (saline; Expt. #1,3), or 400 (Expt. #1,2) or 800 (Expt. #3) ng/kg/min Ang II; simultaneously, in Expt. #2, the diet was switched from 0.4% (standard) to 2% NaCl (HS). BPs were monitored every 3-4 days for up to 4 weeks. Also, in Expt. #2, on day 21, all mice received 2 ip injections, 4 hrs apart, of 10 mg/kg DigiFab, Fab fragments that immuno-neutralize ouabain, while BP was continuously monitored; on day 23, the mice received 2 ip injections of CroFab, anti-crotalus toxin (‘control’) Fab fragments. Results: 1. Basal mean BP (MBP) was 10±2 mm Hg higher in α2 R/R than in WT mice ( P <0.01; n =21 & 29; ANOVA). 2. In WT mice, 400 ng/kg/min sc Ang II and Ang II+HS raised MBP by 15±1 and 34±1 mm Hg, respectively ( P <0.01; n =7-8; ANOVA). 3. The MPB elevation in Ang II+HS α2 R/R (17±2 mm Hg) was only half that in WT mice ( P <0.01; n =7 each; ANOVA). 4. DigiFab rapidly (<1 hr) reduced MBP by 14±2 mm Hg in Ang II+HS hypertensive WT mice ( P <0.001; n =7; T-test), but not in α2 R/R mice ( P <0.01; n =7 each; ANOVA); CroFab did not lower MBP in either strain. 5. 800 ng/kg/min sc Ang II elevated systolic BP by 55±3 mm Hg in WT mice, but by only 37±3 mm Hg in α2 R/R mice ( P <0.05; n =3-5; ANOVA). Conclusions: Ouabain-sensitive α2 Na + pumps and their endogenous ligand are both required for full expression of low-dose Ang II-salt hypertension. Ouabain-sensitive α2 pumps apparently also contribute to high-dose Ang II-hypertension.

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M211. NEUROPROTECTIVE EFFECT OF SHI-ZHEN-AN-SHEN-TANG, A CHINESE HERB FORMULA ON MICE EXPOSED TO CUPRIZONE

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.523 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S216-S217

Author(s):

Chao Ma ◽

Yan Wu ◽

Pei Chen ◽

Yuan Jia ◽

Dongqing Yin ◽

...

Keyword(s):

Low Dose ◽

Neuroprotective Effect ◽

Chinese Herb ◽

Large Body ◽

High Dose ◽

Neuregulin 1 ◽

The Brain ◽

Different Doses ◽

Medium Dose

Abstract Background Our previous study indicated a therapeutic effect of Shi-Zhen-An-Shen-Tang (SZAST), a Chinese herb formula, on schizophrenia, but the related mechanism is unknown(citation). A large body of evidence suggests the important role of white matter of the brain in the pathophysiology of schizophrenia. This study was designed to evaluate the effect of SZAST on schizophrenia with demyelinated mice. Methods Male C57BL/6 mice were given mixed cuprizone (CPZ, a copper chelator, 0.2 %, w/w) rodent chow for six successive weeks to induce demyelination. During the last two weeks, mice were given an oral gavage of saline, or SZAST of three different doses (a low dose of 5.5g·kg-1·d-1, a medium dose of 8.24g·kg-1·d-1, or a high dose of 10.98 g·kg-1·d-1), or quetiapine, respectively. Behavioral tests were conducted after the last treatment. Meanwhile, the expression of myelin basic protein (MBP) and neuregulin-1(NRG1) in the brain was tested by immunohistochemistry staining or Western Blot. Results Mice exposed to CPZ for six weeks showed obvious schizophrenia-like behaviors, including lower nest-building activity, sensory gating activity, and higher locomotor activity. CPZ-fed mice also displayed a lower myelin density in the corpus callosum, hippocampus, and cerebral cortex and a reduction of MBP and NRG1 protein in the hippocampus compared with controls. Both quetiapine and SZAST significantly alleviated the abnormal schizophrenia-like behaviors and the impairment of myelin sheath in CPZ-fed mice, however, SZAST with medium dose showed better neuroprotective effect than the low dose or the high dose of SZAST. Furthermore, the expression of NRG1protein in the hippocampus was slightly, but not significantly increased in all SZAST-treated and quetiapine-treated groups. Discussion These results indicate that the neuroprotective effect of SZAST in demyelinated mice might partially relate to remyelination in the hippocampus in CPZ-fed mice.

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