scholarly journals Altered central TRPV4 expression and lipid raft association related to inappropriate vasopressin secretion in cirrhotic rats

2009 ◽  
Vol 296 (2) ◽  
pp. R454-R466 ◽  
Author(s):  
Flávia Regina Carreño ◽  
Lisa L. Ji ◽  
J. Thomas Cunningham
Keyword(s):  
Lipid Raft ◽  
Supraoptic Nucleus ◽  
Molecular Mechanisms ◽  
Bile Duct Ligation ◽  
Plasma Osmolality ◽  
Plasma Renin ◽  
Duct Ligation ◽  
The Central Nervous System ◽  
Vasopressin Secretion ◽  
The Brain

Inappropriate vasopressin (AVP) release causes dilutional hyponatremia in many pathophysiological states such as cirrhosis. The central molecular mechanisms that mediate inappropriate AVP release are unknown. We tested the hypothesis that changes in the expression or trafficking of TRPV4 in the central nervous system may contribute to inappropriate AVP release in the bile duct ligation (BDL) model of cirrhosis in the rat. Four weeks after surgery, BDL rats demonstrated significantly increased plasma vasopressin and plasma renin activity (PRA), hypervolemia, and decreased plasma osmolality. These effects were blocked by providing BDL rats with 2% saline to drink for 15 days. TRPV4 protein expression was significantly increased in brain punches from BDL rats containing the supraoptic nucleus (SON) of the hypothalamus (100% ± 11 to 157% ± 4.8), and this effect was blocked in BDL rats given saline. Immunohistochemistry demonstrated a significant increase in TRPV4-positive cells and the percentage of AVP neurons that also were TRPV4-positive in the SON of BDL rats. In the hypothalamus of BDL rats, TRPV4 lipid raft association increased compared with sham (from 100% ± 2.1 to 326.1% ± 16). This effect was significantly attenuated in BDL rats given 2% saline to drink (174% ± 11). In the brain stem, TRPV4 lipid raft association was reduced by BDL and inversely related to plasma AVP and PRA. We speculate that changes in TRPV4 expression and compartmentalization within lipid rafts could contribute to a feed-forward mechanism related to AVP release in cirrhosis.

scholarly journals Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiangyue Zhou ◽  
Youwei Li ◽  
Cameron Lenahan ◽  
Yibo Ou ◽  
Minghuan Wang ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Glymphatic System ◽  
System A ◽  
Function Recovery ◽  
The Central Nervous System ◽  
The Stability ◽  
The Brain

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 3

Psychiatry ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 125-134
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Microglial Cells ◽  
Inflammatory Reactions ◽  
Mental Diseases ◽  
The Central Nervous System ◽  
The Brain

Background: at present, the important role of the monocyte-macrophage link of immunity in the pathogenesis of mental diseases has been determined. In the first and second parts of our review, the cellular and molecular mechanisms of activation of monocytes/macrophages, which secreting proinflammatory CD16 receptors, cytokines, chemokines and receptors to them, in the development of systemic immune inflammation in the pathogenesis of somatic diseases and mental disorders, including schizophrenia, bipolar affective disorder (BAD) and depression were analyzed. The association of high levels of proinflammatory activity of monocytes/macrophages in patients with mental disorders with somatic comorbidity, including immune system diseases, is shown. It is known that proinflammatory monocytes of peripheral blood, as a result of violation of the integrity of the hematoencephalic barrier can migrate to the central nervous system and activate the resident brain cells — microglia, causing its activation. Activation of microglia can lead to the development of neuroinammation and neurodegenerative processes in the brain and, as a result, to cognitive disorders. The aim of review: to analyze the results of the main scientific studies concerning the role of cellular and molecular mechanisms of peripheral blood monocytes interaction with microglial cells and platelets in the development of neuroinflammation in the pathogenesis of mental disorders, including Alzheimer’s disease (AD). Material and methods: keywords “mental disorders, AD, proinflammatory monocytes, microglia, neuroinflammation, cytokines, chemokines, cell adhesion molecules, platelets, microvesicles” were used to search for articles of domestic and foreign authors published over the past 30 years in the databases PubMed, eLibrary, Science Direct and EMBASE. Conclusion: this review analyzes the results of studies which show that monocytes/macrophages and microglia have similar gene expression profiles in schizophrenia, BAD, depression, and AD and also perform similar functions: phagocytosis and inflammatory responses. Monocytes recruited to the central nervous system stimulate the increased production of proinflammatory cytokines IL-1, IL-6, tumor necrosis factor alpha (TNF-α), chemokines, for example, MCP-1 (Monocyte chemotactic protein-1) by microglial cells. This promotes the recruitment of microglial cells to the sites of neuronal damage, and also enhances the formation of the brain protein beta-amyloid (Aβ). The results of modern studies are presented, indicating that platelets are involved in systemic inflammatory reactions, where they interact with monocytes to form monocyte-platelet aggregates (MTA), which induce the activation of monocytes with a pro inflammatory phenotype. In the last decade, it has been established that activated platelets and other cells of the immune system, including monocytes, detached microvesicles (MV) from the membrane. It has been shown that MV are involved as messengers in the transport of biologically active lipids, cytokines, complement, and other molecules that can cause exacerbation of systemic inflammatory reactions. The presented review allows us to expand our knowledge about the cellular and molecular aspects of the interaction of monocytes/macrophages with microglial cells and platelets in the development of neuroinflammation and cognitive decline in the pathogenesis of mental diseases and in AD, and also helps in the search for specific biomarkers of the clinical severity of mental disorder in patients and the prospects for their response to treatment.

Regulation of vasopressin secretion in a patient with chronic hypernatraemia

1985 ◽  
Vol 110 (3) ◽  
pp. 346-351 ◽  
Author(s):  
Simon Smitz ◽  
Jean-Jacques Legros
Keyword(s):  
Hypertonic Saline ◽  
Arginine Vasopressin ◽  
Plasma Osmolality ◽  
Concomitant Increase ◽  
Specific Radioimmunoassay ◽  
Vasopressin Secretion ◽  
Plasma Arginine ◽  
The Brain ◽  
Unrestricted Diet ◽  
Hypertonic Saline Infusion

Abstract. A patient with the chronic hypernatraemia syndrome is described. Using a sensitive and specific radioimmunoassay, the plasma arginine-vasopressin (AVP) level was measured under various conditions. With an unrestricted diet, the plasma AVP level was inappropriately low for the degree of plasma hyperosmolality (0.9 pmol/l and 302 mOsm/kg, respectively). After chronic water loading, plasma osmolality was 271 mOsm/kg, plasma AVP level 1.5 pmol/l, and the urine remained hypertonic with respect to the plasma. During hypertonic saline infusion, plasma osmolality increased from 271 to 294 mOsm/kg without a concomitant increase in the plasma AVP concentration. After sc injection of apomorphine and after haemodynamic stimulation, the plasma AVP concentration increased from 0.8 to 36 pmol/l and from 1.2 to 6.3 pmol/I, respectively. These data demonstrate a selective deficiency in the osmoregulation of the AVP secretion. The observed neuroendocrine abnormalities may be linked to a congenital malformation of the brain.

scholarly journals Methamphetamine-Triggered Neurotoxicity in Human Dorsolateral Prefrontal Cortex

2021 ◽  
Vol 10 ◽  
pp. 2016
Author(s):  
Ali Zare ◽  
Alireza Ghanbari ◽  
Mohammad Javad Hoseinpour ◽  
Mahdi Eskandarian Boroujeni ◽  
Alimohammad Alimohammadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Metabolic Activation ◽  
Neural Cells ◽  
Dorsolateral Prefrontal ◽  
The Central Nervous System ◽  
The Brain

Background: Methamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity. Materials and Methods: In this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content. Results: The expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Discussion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity. [GMJ.2021;10:e2016]

scholarly journals Primary Amoebic Meningoencephalitis by Naegleria fowleri: Pathogenesis and Treatments

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1320 ◽  
Author(s):  
Andrea Güémez ◽  
Elisa García
Keyword(s):  
Molecular Mechanisms ◽  
Case Reports ◽  
Naegleria Fowleri ◽  
Initial Exposure ◽  
Immunomodulatory Agents ◽  
Primary Amoebic Meningoencephalitis ◽  
The Central Nervous System ◽  
Nægleria Fowleri ◽  
Amoebic Meningoencephalitis ◽  
The Brain

Naegleria fowleri is a free-living amoeba (FLA) that is commonly known as the “brain-eating amoeba.” This parasite can invade the central nervous system (CNS), causing an acute and fulminating infection known as primary amoebic meningoencephalitis (PAM). Even though PAM is characterized by low morbidity, it has shown a mortality rate of 98%, usually causing death in less than two weeks after the initial exposure. This review summarizes the most recent information about N. fowleri, its pathogenic molecular mechanisms, and the neuropathological processes implicated. Additionally, this review includes the main therapeutic strategies described in case reports and preclinical studies, including the possible use of immunomodulatory agents to decrease neurological damage.

Alcohol Dementia, Wernicke’s Encephalopathy, and Korsakoff’s Syndrome

2019 ◽  
pp. 742-758
Author(s):  
Marlene Oscar-Berman, ◽  
Nasim Maleki
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Complications ◽  
Wernicke’S Encephalopathy ◽  
Wernicke's Encephalopathy ◽  
Korsakoff’S Syndrome ◽  
Emotional Processes ◽  
Korsakoff's Syndrome ◽  
Neuropsychological Characteristics ◽  
The Central Nervous System ◽  
The Brain

Chronic alcohol consumption has direct effects on the central nervous system and is among the leading causes of cognitive impairment and dementia. Alcohol-related dementia, Wernicke’s encephalopathy, and Korsakoff’s syndrome are among the most common forms of severe alcoholism-related neurological complications that are associated with widespread abnormalities in the brain, as well as impairments of multiple mental and emotional processes. Abnormalities have been consistently reported in association with Wernicke’s encephalopathy and Korsakoff’s syndrome, but alcohol-related dementia remains less well characterized. This chapter reviews the neurological and neuropsychological characteristics of these conditions, associated changes in the brain, potential molecular mechanisms involved, and some of the treatment or rehabilitation options. Future use of evidence-based diagnostic test-selection is advised to assist in refining differential diagnoses.

Origin, utilization, and recycling of nucleosides in the central nervous system

2011 ◽  
Vol 35 (4) ◽  
pp. 342-346 ◽  
Author(s):  
Piero Luigi Ipata
Keyword(s):  
Extracellular Space ◽  
Active Sites ◽  
Molecular Mechanisms ◽  
Brain Cell ◽  
Nucleoside Triphosphate ◽  
Pyrimidine Salvage ◽  
The Central Nervous System ◽  
Hydrolysis Of ◽  
The Brain ◽  
Brain Extracellular Space

The brain relies on the salvage of preformed purine and pyrimidine rings, mainly in the form of nucleosides, to maintain its nucleotide pool in the proper qualitative and quantitative balance. The transport of nucleosides from blood into neurons and glia is considered to be an essential prerequisite to enter their metabolic utilization in the brain. Recent lines of evidence have also suggested that local extracellular nucleoside triphosphate (NTP) degradation may contribute to brain nucleosides. Plasma membrane-located ectonucleotidases, with their active sites oriented toward the extracellular space, catalyze the successive hydrolysis of NTPs to their respective nucleosides. Apart from the well-established modulation of ATP, ADP, adenosine (the purinergic agonists), UTP, and UDP (the pyrimidinergic agonists) availability at their respective receptors, ectonucleotidases may also serve the local reutilization of nucleosides in the brain. After their production in the extracellular space by the ectonucleotidase system, nucleosides are transported into neurons and glia and converted back to NTPs via a set of purine and pyrimidine salvage enzymes. Finally, nucleotides are transported into brain cell vescicles or granules and released back into the extracellular space. The key teaching concepts to be included in a two-to three-lecture block on the molecular mechanisms of the local nucleoside recycling process, based on a cross talk between the brain extracellular space and cytosol, are discussed in this article.

Indirect hypertensive actions of long-term intracarotid angiotensin II infusion during ovine pregnancy

1994 ◽  
Vol 72 (4) ◽  
pp. 311-316 ◽  
Author(s):  
S. C. Mukaddam-Daher ◽  
G. W. Aberdeen ◽  
S. C. Cha ◽  
J. Gutkowska ◽  
B. S. Nuwayhid ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Urine Volume ◽  
Plasma Renin ◽  
Sodium Balance ◽  
Angiotensin System ◽  
The Central Nervous System ◽  
The Brain ◽  
Internal Carotid Arteries

Angiotensin II (AngII) influences the regulation of mean arterial pressure (MAP) through numerous mechanisms, including an action of circulating AngII on the brain to alter autonomic activity. We have obtained evidence that the relative importance of this effect is increased during pregnancy. Consequently, these studies were undertaken to assess the effects of bilateral infusion of AngII (0.35 ng∙kg−1∙min−1∙artery−1) into the internal carotid arteries (ica) of sheep for 13 days. Six nonpregnant (NP) and six 105- to 125-day pregnant (PG) ewes were maintained in large metabolism cages, where MAP was continuously monitored. By day 10 of ica AngII infusion in NP ewes, MAP was increased from 83.9 ± 1.6 to 92.9 ± 2.8 mmHg (1 mmHg = 133.3 Pa) (p = 0.001). Twenty-four hour urine volume (UV, 2664 ± 341 to 1583 ± 228 mL; p = 0.005) and sodium excretion (UNaV, 190 ± 5 to 113 ± 19 mmol/day; p = 0.005) were decreased. 51Cr-tagged blood volume (BV) was increased on day 13 (3643 ± 187 to 4379 ± 446 mL; p = 0.05). In contrast, by only day 6 of ica AngII infusion in PG ewes, MAP increased from 79.1 ± 1.9 to 84.1 ± 1.4 mmHg (p = 0.03) in association with a BV expansion from 3999 ± 274 to 4207 ± 275 mL. These changes were preceded by decreases in UV (2813 ± 413 to 2198 ± 362 mL; p = 0.01) and UNaV (190 ± 15 to 118 ± 26 mmol/day; p = 0.01). By day 13, MAP had plateaued at 93.0 ± 1.2 mmHg. There were no changes in plasma AngII, plasma renin activity, arginine vasopressin, and atrial natriuretic factor during ica AngII infusion in either NP or PG ewes, suggesting that these effects are mediated via the central nervous system. Moreover, the data suggest that MAP is increased secondary to volume expansion associated with sodium and water retention. This effect appears to be more readily exhibited during pregnancy. Furthermore, this study demonstrates the importance of the rennin–angiotensin system in blood pressure homeostasis by actions other than direct vasoconstriction.Key words: angiotensin II, blood pressure, hypertension, sheep, pregnancy, sodium balance.

scholarly journals The Central Nervious System Acts as a Transducer of Stress-Induced Masculinization through Corticotropin-Releasing Hormone B

2018 ◽  
Author(s):  
DC Castañeda Cortés ◽  
LF Arias Padilla ◽  
VS Langlois ◽  
GM Somoza ◽  
JI Fernandino
Keyword(s):  
Molecular Mechanisms ◽  
Sex Reversal ◽  
Environmental Stressors ◽  
Mrna Levels ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Downstream Effector ◽  
The Central Nervous System ◽  
First Time ◽  
The Brain

ABSTRACTExposure to environmental stressors during early development has important implications for rescheduling many cellular and molecular mechanisms. In some fish species, environmental stressors, like high temperatures (HT), cause an increase in cortisol levels. In turn, this mechanism induces sex reversal of genotypic females, overriding genetic factors related to development of the gonad. However, the involvement of the brain in this process is not well clarified. In the present work, we investigated the mRNA levels of corticotropin-releasing hormone b (crhb) and its receptors (crhr1 and crhr2), and found out that they were up-regulated at HT during the critical period of gonadal sex determination in medaka (Oryzias latipes), i.e., when the gonadal primordium is sexually labile. In order to clarify their roles in sex reversal, biallelic mutants for crhr1 and crhr2 were produced by CRISPR/Cas9 technology. Remarkably, biallelic mutant of both loci (crhr1 and crhr2) did not undergo female-to-male sex reversal upon HT exposition, whereas mutants for either crhr1 or crhr2 showed partial, or intersex phenotypes, suggesting that both crh receptors are required for HT-induced masculinization. Inhibition of this process in double crhrs mutants could be successfully rescued through the administration of the downstream effector of the hypothalamic-pituitary interrenal axis, the cortisol. Taken together, these results revealed for the first time the participation of the central nervous system acting as a transducer of masculinization induced by thermal stress.

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