Int J Physiol Pathophysiol Pharmacol [JOURNAL]
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200 papers
Low-dose ethanol excites lateral habenula neurons projecting to VTA, RMTg, and raphe.
Fu R, Mei Q, Zuo W … +4 more , Li J, Gregor D, Bekker A, Ye J
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348799
It is unclear how social drinking can contribute to the development of addiction in susceptible individuals. However, alcohol's aversive properties are a well-known factor contributing to its abuse. The lateral habenula...
It is unclear how social drinking can contribute to the development of addiction in susceptible individuals. However, alcohol's aversive properties are a well-known factor contributing to its abuse. The lateral habenula (LHb) is a key brain structure responding to various aversive stimuli, including those related to alcohol. We recently reported that ethanol at 10 mM or less that can be achieved by social drinking activates many LHb neurons and drives aversive conditioning. The current study sought to identify LHb circuits that are activated by a low-dose of ethanol using immunohistochemistry and anatomic tracing techniques on adult Sprague-Dawley rats. We showed here that an intraperitoneal injection of ethanol (0.25 g/kg), resulting in a blood ethanol concentration of 5.6 mM, significantly increased the number of cFos immunoreactive (IR) neurons in the LHb. Most of the ethanol-activated cFos-IR LHb neurons expressed vGluT2 (vesicular glutamate transporters 2, a marker of a glutamatergic phenotype). These LHb neurons projected to the ventral tegmental area (VTA), rostromedial tegmental nucleus (RMTg), and dorsal raphe. Moreover, injections of the anterograde tracer AAV-CaMKIIa-eGFP into the lateral hypothalamus produced a significant amount of labeled fibers with vGluT2 positive terminals on the ethanol-activated LHb cells. These results indicate that the LHb neurons stimulated by a low-dose of ethanol project to the VTA, RMTg, and dorsal raphe, and receive excitatory projections from the lateral hypothalamus. These neurocircuits may play a crucial role in mediating the initial aversive effects produced by a low-dose of ethanol.
TRPM7 is a unique target for therapeutic intervention of stroke.
Lin J, Xiong ZG
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348798
Ischemic stroke is a leading cause of death and long-term disabilities. The current therapy is limited to thrombolysis and mechanical recanalization, which have limited success. A better understanding of the mechanisms u...
Ischemic stroke is a leading cause of death and long-term disabilities. The current therapy is limited to thrombolysis and mechanical recanalization, which have limited success. A better understanding of the mechanisms underlying ischemic brain injury is therefore needed for the development of more effective interventions. Glutamate receptor-mediated Ca overload and neurotoxicity have been well established for decades. However, clinical trials failed to show a satisfactory effect with the antagonists of glutamate receptors. Other glutamate-independent mechanisms, such as activation of acid-sensing ion channels and transient receptor potential melastatin 7 (TRPM7), have recently emerged as important events responsible for neuronal injury under ischemic conditions. In this review, we discuss how TRPM7 channels participate in ischemic brain injury.
Experimentally-induced ventricular arrhythmias.
Merrill GF
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348797
Hypoxia and reoxygenation, ischemia and reperfusion, catecholamine infusion, ouabain, sodium pentobarbital and caffeine, can all be used experimentally to induce ventricular arrhythmias. According to the Lambeth Conventi...
Hypoxia and reoxygenation, ischemia and reperfusion, catecholamine infusion, ouabain, sodium pentobarbital and caffeine, can all be used experimentally to induce ventricular arrhythmias. According to the Lambeth Convention guidelines our experimentally-induced ventricular arrhythmias include but are not limited to: ventricular premature beats (VPB), ventricular salvos (VS), ventricular bigeminy (VB), nonsustained ventricular tachycardia (VTn), sustained ventricular tachycardia (VTs) and ventricular fibrillation (VF, or if the heart is not defibrillated, sudden cardiac death). We have studied these arrhythmias in the absence and presence of adenosine deaminase, methyl xanthines, and more recently, acetaminophen. Our laboratory was the first to discover the anti-arrhythmic properties of acetaminophen an analgesic used in Western medicine for more than 100 years before our publication. We have also identified other cardioprotective properties of acetaminophen, and have begun to work out some of the cellular/molecular mechanisms. For example, we know that acetaminophen protects hypoxic/ischemic cardiac mitochondria, in part, by sustaining function of the mitochondrial permeability transition pore (MPTP, a protein involved in regulating mitochondrial pH). Acetaminophen also attenuates the actions of matrix metalloproteinases that can be harmful to myocardial contractile proteins. Of course, like all science, more work is needed to expand on these and related topics.
Condition-specific transcriptional regulation of neuronal ion channel genes in brain ischemia.
Hernandez-Encarnacion L, Sharma P, Simon R … +1 more , Zhou A
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348796
In the context of seeking novel therapeutic targets for treating ischemic stroke, the preconditioning ischemia-induced brain ischemic tolerance has been used as a model of endogenously operative, broad-based neuroprotect...
In the context of seeking novel therapeutic targets for treating ischemic stroke, the preconditioning ischemia-induced brain ischemic tolerance has been used as a model of endogenously operative, broad-based neuroprotective mechanisms. Targeting such mechanisms is considered potentially less prone to adverse side effects, as those seen in many failed clinical trials that focus on single targets using exogenous compounds. Results from previous studies have revealed an overall decrease in potassium channel activity in tolerance development. The objective of this study is to identify ion channel genes that are differentially regulated under different brain ischemic conditions, as a mean to identify those ion channels that are associated with ischemic brain injury and ischemic tolerance. In mice in vivo, transient focal cerebral ischemia was induced by middle cerebral artery occlusion. In cultured neuronal cells in vitro, simulated ischemia was modeled by oxygen-glucose deprivation. For both in vivo and in vitro studies, three principal ischemic conditions were included: ischemic-preconditioned, injured and tolerant, respectively, plus appropriate controls. In these model systems, transcript levels of a panel of 84 neuronal ion channels genes were analyzed with a quantitative real-time PCR mini-array. The results showed that, both in vivo and in vitro, there was a predominant down regulation in neuronal ion channel genes under ischemic-tolerant conditions, and an up regulation in ischemic injury. Similar changes were observed among potassium, sodium and calcium channel genes. A number of regulated genes exhibited opposing changes under ischemic-injured and ischemic-tolerant conditions. This subset of ion channel genes exemplifies potentially novel leads for developing multi-factorial therapeutic targets for treating ischemic stroke.
Therapeutic angiogenesis of exosomes for ischemic stroke.
Manuel GE, Johnson T, Liu D
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348795
Angiogenesis is the process through which new blood vessels are formed, while therapeutic angiogenesis aims to promote and control the angiogenic response. Ischemia results from the lack of blood flow with oxygen and nut...
Angiogenesis is the process through which new blood vessels are formed, while therapeutic angiogenesis aims to promote and control the angiogenic response. Ischemia results from the lack of blood flow with oxygen and nutrients. Therapeutic angiogenesis is crucial in preserving brain tissue and bodily functions after ischemic stroke. Various approaches have been proposed to promote angiogenesis in ischemic diseases. Traditional protein/gene and subsequent stem/progenitor cell approaches have not shown consistent efficacy for ischemic diseases in clinical trials. Exosomes are microparticles secreted from cells and conduct cell-cell communication including stem cell or cancer cell induced pro-angiogenesis. Utilization of exogenous exosomes for the treatment of ischemic diseases is an emerging approach which may prevent certain disadvantages such as easy degradation and tumor formation happened in other strategies. This review highlights recent reports on the use of exosomes as a therapeutic agent to promote angiogenesis in ischemic stroke.
Tubby-like protein 1 (Tulp1) is a target of microRNA-134 and is down-regulated in experimental epilepsy.
Rodriguez AS, Engel T, Palfi A … +3 more , Farrar GJ, Henshall DC, Jimenez-Mateos EM
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348794
MicroRNAs are important determinants of gene expression via post-transcriptional control of the protein levels of their mRNA targets. MicroRNA-134 (miR-134) has emerged as an important brain-specific microRNA which has b...
MicroRNAs are important determinants of gene expression via post-transcriptional control of the protein levels of their mRNA targets. MicroRNA-134 (miR-134) has emerged as an important brain-specific microRNA which has been implicated in the control of dendritic spine morphology, neuronal differentiation and apoptosis. Here we show that Tubby-like protein 1 (Tulp1) is a target of miR-134. Tulp1 protein showed a similar cellular distribution pattern in the hippocampus to miR-134 and displayed an inverse expression pattern in the mouse retina. Bioinformatics analyses identified a conserved miR-134 binding site in the 3' untranslated region of both mouse and human and luciferase reporter assays confirmed miR-134 targets Tulp1 in vitro. Induction of prolonged seizures in mice resulted in upregulation of miR-134 and downregulation of protein levels of Tulp1 which were reversed in animals injected with locked nucleic acid-modified antagomirs targeting miR-134. Finally, knockdown of Tulp1 in human neurons caused an increase in vulnerability to excitotoxicity. These data identify Tulp1/TULP1 as a novel target of miR-134, which may contribute to underlying pathomechanisms in epilepsy.
Inflammasome in drug abuse.
Xu E, Liu J, Wang X … +1 more , Xiong H
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29348793
Drug abuse disorders refer to a set of related negative health implications associated with compulsive drug seeking and use. Because almost all addictive drugs act on the brain, many of them cause neurological impairment...
Drug abuse disorders refer to a set of related negative health implications associated with compulsive drug seeking and use. Because almost all addictive drugs act on the brain, many of them cause neurological impairments after long-term abuse. Neuropathological studies have revealed a widespread impairment of the cellular elements. As the key components to limit the damage of neural cells, CNS immune system is also found affected by these drugs, directly or indirectly. It has been shown that drugs of abuse alter neuroimmune gene expression and signaling. Growing studies on neuroimmune factors further demonstrate their indispensable role in drugs-induced neurotoxicity. As an important proinflammatory intracellular receptor, inflammasome is activated in many neurodegenerative diseases in response to a broad range of damage-associated molecular patterns (DAMPs) signals. In the cases of drug abuse, especially in those with comorbid of HIV infection and sustained pain, inflammasome activation significantly promotes the neuroinflammation-associated toxicities. To understand inflammasome in drug-associated neurotoxic activity, we reviewed the role played by inflammasome in drug abuse-induced microglial neurotoxicity and evaluated the potential of imflammasone as a therapeutic target for drug abuse disorders based on recent development of various selective small-molecular inflammasome inhibitors.
Erratum: New insights and new hope for pulmonary arterial hypertension: natriuretic peptides clearance receptor as a novel therapeutic target for a complex disease.
Egom EE, Feridooni T, Pharithi RB … +7 more , Khan B, Shiwani HA, Maher V, El Hiani Y, Rose RA, Pasumarthi KB, Ribama HA
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29218116
[This corrects the article on p. 112 in vol. 9, PMID: 28951773.].
[This corrects the article on p. 112 in vol. 9, PMID: 28951773.].
Statistical methods and common problems in medical or biomedical science research.
Yan F, Robert M, Li Y
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29209453
Statistical thinking is crucial for studies in medical and biomedical areas. There are several pitfalls of using statistics in these areas involving in experimental design, data collection, data analysis and data interpr...
Statistical thinking is crucial for studies in medical and biomedical areas. There are several pitfalls of using statistics in these areas involving in experimental design, data collection, data analysis and data interpretation. This review paper describes basic statistical design problems in biomedical or medical studies and directs the basic scientists to better use of statistical thinking. The contents of this paper were based on previous literatures and our daily basic support work. It includes the sample size determination and sample allocation in experimental design stage, numerical and graphical data summarization, and statistical test methods as well as the related common errors at design and analytic stages. Literatures and our daily support works show that misunderstanding and misusing of statistical concept and statistical test methods are significant problems. These may include ignoring the sample size and data distribution, incorrect summarization measurement, wrong statistical test methods especially for repeated measures, ignoring the assumption for t-test or ANOVA test, failing to perform the adjustment for multiple comparison. This review intends to help the researchers in basic medical or biomedical areas to enhance statistical thinking and make fewer errors in study design and analysis of their studies.
Protective roles of hepatic GABA signaling in liver injury.
Wang S, Zhang L, Liu C … +1 more , Lu WY
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29209452
In addition to functioning as a neurotransmitter, γ-aminobutyric acid (GABA) generates signals, via its type A or type B receptors (GABARs or GABARs), in various types of cells. Studies, including ours, show that GABAR-m...
In addition to functioning as a neurotransmitter, γ-aminobutyric acid (GABA) generates signals, via its type A or type B receptors (GABARs or GABARs), in various types of cells. Studies, including ours, show that GABAR-mediated auto- and paracrine GABAergic signaling occurs in rodent hepatocytes and cholangiocytes, protecting the liver against toxic injuries. This short article briefly introduces the GABA signaling system in rodent livers and discusses potential mechanisms by which the hepatic GABA signaling protects the liver function.
miR-149 reduces while let-7 elevates ASIC1a expression in vitro.
Jiang YQ, Zha XM
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29209451
Acid-sensing ion channel 1a (ASIC1a) is the key subunit that determines acid-activated currents in neurons. ASIC1a is important for neural plasticity, learning, and for multiple neurological diseases, including stroke, m...
Acid-sensing ion channel 1a (ASIC1a) is the key subunit that determines acid-activated currents in neurons. ASIC1a is important for neural plasticity, learning, and for multiple neurological diseases, including stroke, multiple sclerosis, and traumatic injuries. These findings underline the importance for better defining mechanisms that regulate ASIC1a expression. During the past decade, microRNA has emerged as one important group of regulatory molecules in controlling protein expression. However, little is known about whether microRNA regulates ASIC1a. Here, we assessed several microRNAs that have predicted targeting sequences in the 3' untranslated region (UTR) of mouse ASIC1a. Our results indicated that miR-144 and -149 reduced ASIC1a expression while Let-7 increased ASIC1a protein levels. miR-30c, -98, -125, -182* had no significant effect. Since a reduction in ASIC1a expression may have translational potentials in treating neuronal injury, we further asked whether the effect of miR-144 and miR-149, both reduced ASIC1a expression, was through specific targeting of the predicted sites on ASIC1a. We mutated the targeting sequence of miR-144 and miR-149 in ASIC1a UTR. The effect of miR-149 was abolished in the corresponding mutation. In contrast, miR-144 still reduced ASIC1a level when its predicted target sequence was mutated. This result indicates that miR-149 targets the 3'UTR of ASIC1a and reduces its expression.
Zinc chelation promotes streptokinase-induced thrombolysis .
Wang Z, Yu X, Li YV
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29209450
Cardiovascular disorder occurs when a local blood clot obstructs an artery or a vein to its surround organs, causing related tissues to lose function and die. It is one of the leading causes of mortality and a major caus...
Cardiovascular disorder occurs when a local blood clot obstructs an artery or a vein to its surround organs, causing related tissues to lose function and die. It is one of the leading causes of mortality and a major cause of disability. The effect of thrombolysis induced by injecting intravenous thrombolytic agents is critical for reducing tissue damages. Streptokinase (SK) is a widely used thrombolytic agent in the treatment of thromboembolism in the blood vessels. A high unit of streptokinase is used in thrombolytic therapies for thrombotic disorders and could improve tissue reperfusion. It is a potent plasminogen activator. However, safety concerns for the usage of a high unit of streptokinase have been raised for the hemorrhagic transformation. In the present study, we studied how zinc would affect streptokinase-induced thrombolysis , and proposed a strategy to improve streptokinase's effectiveness in promoting thrombolysis. The mice whole blood was used to form the blood clot by incubating with calcium at 37°C for 30 minutes. Streptokinase was used for inducing thrombolysis measured with the spectrophotometer. Zinc and its chelator, Ca-EDTA, were applied with streptokinase, respectively. Results showed that the co-application zinc inhibited the thrombolytic effect of streptokinase in a dose-dependent manner. Zinc chelator, Ca-EDTA, significantly increased the effect of streptokinase-induced thrombolysis. Our results suggest that zinc chelation improved the efficiency of streptokinase in thrombolysis. The results may have a significant clinical implication by potentially reducing the adverse effect of streptokinase application.
Effect of oleanolic acid on small intestine morphology and enzymes of glutamine metabolism in diabetic rats.
Isah MB, Masola B
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 29209449
The small intestine (SI) is the main site for food absorption and glutamine utilization hence critical in metabolic disorders that involve energy balance such as diabetes. This study investigates the effects of oleanolic...
The small intestine (SI) is the main site for food absorption and glutamine utilization hence critical in metabolic disorders that involve energy balance such as diabetes. This study investigates the effects of oleanolic acid (OA) on SI morphology and some enzymes of glutamine metabolism in male Sprague-Dawley diabetic rats. High dose STZ-induced diabetes (HDD) and low dose STZ-induced diabetes (LDD) were induced by intraperitoneal injection of 60 and 40 mg streptozotocin/kg body weight respectively. Non-diabetic and diabetic rats were treated for two weeks with OA, insulin or OA + insulin in HDD study while animals in the in LDD study were treated with OA. There was significant (P<0.05) increase in the weight of the SI of diabetic animals and of villus height (VH) in the jejunum and duodenum of HDD animals. OA and insulin treatment significantly decreased VH in duodenum of HDD animals while OA treatment profoundly increased VH in normal rats. Jejunal of phosphate-dependent glutaminase (PDG) activity was unaffected by diabetes however alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were significantly (P<0.05) elevated by diabetes and treatments decreased these elevated aminotransferase activities. It is suggested that the intestine meets the energy demand in diabetes by modulating the activities of aminotransferases without change in PDG activity.
Erratum: Effects of Low-Dose acetazolamide on exercise performance in simulated altitude.
Ernst E, Gatterer H, Burtscher J … +3 more , Faulhaber M, Pocecco E, Burtscher M
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 28951775
[This corrects the article on p. 28 in vol. 9, PMID: 28533889.].
[This corrects the article on p. 28 in vol. 9, PMID: 28533889.].
The effect of epigallocatechin-3-gallate on the renal dysfunction in the obstructed kidney in the rat.
Hammad FT, Lubbad L
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 28951774
INTRODUCTION: Epigallocatechin-3-gallate (EGCG) is the most active catechin polyphenol extracted from the green tea. EGCG has protective effects in various renal and non-renal conditions. The aim of this study was to inv...
INTRODUCTION: Epigallocatechin-3-gallate (EGCG) is the most active catechin polyphenol extracted from the green tea. EGCG has protective effects in various renal and non-renal conditions. The aim of this study was to investigate the effect of EGCG on the alterations in renal functional parameters following reversible unilateral ureteral obstruction (UUO) in the rat. METHODS: Wistar rats underwent reversible left UUO for 72 hours. Group-EGCG (n=10) received intraperitoneal 50 mg/kg/day of EGCG whereas Group-Vx (n=10) had only normal saline. Five days post UUO reversal, renal functions of both kidneys were measured using clearance techniques and the gene expression of some of kidney injury markers (KIM-1 and NGL) and the pro-inflammatory mediator (TNF-α) were determined using real time PCR. RESULTS: Renal blood flow, glomerular filtration rate, urine volume and urinary sodium excretion were still altered 5 days post-UUO reversal. Fractional sodium excretion had returned to baseline values by that time. EGCG did not significantly affect any of the renal functional parameters of the obstructed kidney (P>0.05 for all). However, it significantly decreased the gene expressions of KIM-1, NGAL and TNF-α in the left obstructed kidney in Group-EGCG compared to Group-Vx (28±27 vs. 286±107, 1.1±0.2 vs. 10.9±4.3, and 0.8±0.1 vs. 1.5±0.2, P<0.05 for all). CONCLUSION: EGCG appears to have no significant protective effect on the haemodynamic or tubular glomerular functions when measured as early as five days post reversal of UUO despite the attenuation of some of the kidney injury markers and pro-inflammatory mediators.
New insights and new hope for pulmonary arterial hypertension: natriuretic peptides clearance receptor as a novel therapeutic target for a complex disease.
Egom EE, Feridooni T, Pharithi RB … +7 more , Khan B, Shiwani HA, Maher V, El Hiani Y, Rose RA, Pasumarthi KB, Ribama HA
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 28951773
BACKGROUND: Pulmonary Arterial Hypertension (PAH) is a deadly and disabling disease for which there is no marketed drug that addresses the underlying disease mechanism and targets to cure patients. The lack of understand...
BACKGROUND: Pulmonary Arterial Hypertension (PAH) is a deadly and disabling disease for which there is no marketed drug that addresses the underlying disease mechanism and targets to cure patients. The lack of understanding of the disease mechanism represents the main challenges in developing curative therapies. We here report, for the first time, that mice lacking natriuretic peptides clearance receptor develop PAH. METHODS AND RESULTS: Initial studies assessed cardiac structure and function in NPR-C (wild type) and age matched, littermate NPR-C mice by echocardiography. Mice lacking NPR-C had right atrial dilation, tricuspid regurgitation as well as echocardiographic signs of right ventricular pressure overload, including flattening and paradoxical bulging of the septum into the left ventricle during systole, and hypertrophy of the right ventricular free wall. Among the 10 NPR-C mice aged between 12 and 20 weeks studied, 8 showed the above typical echocardiographic features of PAH [80%, 95% CI: (0.4439-0.9748)], and only one had pericardial effusion [10%, 95% CI: (0.0025-0.4450)], finding that has a prognostic significance in subjects affected by this clinical entity. To confirm the presence of increased right ventricular systolic pressure (RVSP) among NPR-C mice, right heart catheterization was performed. Strikingly, RVSP was significantly elevated in NPR-C mice compared to their age matched, littermate NPR-C mice, at baseline (21.95±0.56 mmHg vs. 5.3±0.6 mmHg, respectively (P<0.001)). CONCLUSION: The above results suggest that NPR-C-mediated signalling pathways play a critical role in the development of PAH, indicating that NPR-C is an important protective receptor in the heart rather than just being a clearance receptor.
Generating CNS organoids from human induced pluripotent stem cells for modeling neurological disorders.
Brawner AT, Xu R, Liu D … +1 more , Jiang P
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 28694921
Understanding human brain development and disease is largely hampered by the relative inaccessibility of human brain tissues. Recent advances in human induced pluripotent stem cells (hiPSCs) have led to the generation of...
Understanding human brain development and disease is largely hampered by the relative inaccessibility of human brain tissues. Recent advances in human induced pluripotent stem cells (hiPSCs) have led to the generation of unlimited human neural cells and thereby facilitate the investigation of human brain development and pathology. Compared with traditional 2-dimensional (2D) culture methods, culturing the hiPSC-derived neural cells in a three-dimensional (3D) free-floating manner generates human central nervous system (CNS) organoids. These 3D CNS organoids possess the unique advantage of recapitulating multi-regional or region-specific cytoarchitecture seen in the early human fetal brain development. The CNS organoids are becoming a strong complement to the animal model in studying brain development and pathology, and developing new therapies to treat neurodevelopmental diseases. Further improvements to the long-term maintenance and neural maturation of the organoids may allow them to model neurodegenerative diseases. In this review, we will summarize the current development of hiPSCs to generate CNS organoids for modeling neurological disorders and future perspective.
Role of microglia in methamphetamine-induced neurotoxicity.
Xu E, Liu J, Liu H … +2 more , Wang X, Xiong H
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 28694920
Methamphetamine (Meth) is an addictive psychostimulant widely abused around the world. The chronic use of Meth produces neurotoxicity featured by dopaminergic terminal damage and microgliosis, resulting in serious neurol...
Methamphetamine (Meth) is an addictive psychostimulant widely abused around the world. The chronic use of Meth produces neurotoxicity featured by dopaminergic terminal damage and microgliosis, resulting in serious neurological and behavioral consequences. Ample evidence indicate that Meth causes microglial activation and resultant secretion of pro-inflammatory molecules leading to neural injury. However, the mechanisms underlying Meth-induced microglial activation remain to be determined. In this review, we attempt to address the effects of Meth on human immunodeficiency virus (HIV)-associated microglia activation both and . Meth abuse not only increases HIV transmission but also exacerbates progression of HIV-associated neurocognitive disorders (HAND) through activation of microglia. In addition, the therapeutic potential of anti-inflammatory drugs on ameliorating Meth-induced microglia activation and resultant neuronal injury is discussed.
8-pCPT-cGMP prevents mitochondrial depolarization and improves the outcome of steatotic partial liver transplantation.
Liu Q, Rehman H, Krishnasamy Y … +2 more , Lemasters JJ, Zhong Z
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 28694919
Permeant cGMP analogs prevent the mitochondria permeability transition (MPT) . In this study, we explored whether 8-pCPT-cGMP prevents the MPT and decreases post-transplant damage to fatty partial liver grafts (FPG) . Ra...
Permeant cGMP analogs prevent the mitochondria permeability transition (MPT) . In this study, we explored whether 8-pCPT-cGMP prevents the MPT and decreases post-transplant damage to fatty partial liver grafts (FPG) . Rats were fed a control or high-fat, high-fructose diet for 2-week. Lean and fatty liver explants were reduced in size to ~35% and stored in the University of Wisconsin solution with and without 8-pCPT-cGMP (300 µM) for 2 h. After transplantation, alanine aminotransferase release (indicator of hepatocellular injury), hyperbilirubinemia (indicator of poor liver function), and cell death were all higher in FPG than in lean partial grafts (LPG). Liver regeneration increased in LPG but was suppressed in FPG. 8-pCPT-cGMP blunted graft injury, improved liver regeneration and function, and increased survival of FPG. Hepatic mitochondrial depolarization detected by intravital multiphoton microscopy of rhodamine 123 in living rats was ~3.5-fold higher in FPG than in LPG. 8-pCPT-cGMP decreased mitochondrial depolarization in FPG almost to the level of LPG. Activation of mammalian target of rapamycin (mTOR), an energy sensitive kinase that stimulates cell proliferation and growth, and p70S6 kinase, a downstream signaling molecule of mTOR, was increased in LPG but suppressed in FPG. 8-pCPT-cGMP restored the activity of mTOR and p70S6 kinase in FPG. 8-pCPT-cGMP also increased activation of cAMP response element-binding protein (CREB) and expression of cyclins D1 and E in FPG. Non-alcoholic steatosis increases injury and suppresses regeneration after partial liver transplantation, at least in part, due to more severe mitochondrial dysfunction. Protection of mitochondria with a cGMP analog effectively improves outcomes of FPG transplantation.
Alteration of circadian rhythm during epileptogenesis: implications for the suprachiasmatic nucleus circuits.
Xiang Y, Li ZX, Zhang DY … +3 more , He ZG, Hu J, Xiang HB
Int J Physiol Pathophysiol Pharmacol · 2017 · PMID 28694918
It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasm...
It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN) circuits in overall circadian rhythm and seizure susceptibility both in animals and humans. Thus, we conclude that SCN circuits may exert modifying effects on circadian rhythmicity and neuronal excitability during epileptogenesis. SCN circuits will be studied in our brain centre and collaborating centres to explore further the interaction between the circadian rhythm and epileptic seizures. More and thorough research is warranted to provide insight into epileptic seizures with circadian disruption comorbidities such as disorders of cardiovascular parameters and core body temperature circadian rhythms.
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