Disturbance Of Water Homeostasis Research Articles

Multifaceted Roles of Aquaporins in the Pathogenesis of Alzheimer’s Disease

The central nervous system is highly dependent on water, and disturbances in water homeostasis can have a significant impact on its normal functions. The regulation of water balance is, at least in part, carried out via specialized water channels called aquaporins. In the central nervous system, two major aquaporins (AQPs), AQP1 and AQP4, and their potential involvements have been long implicated in the pathophysiology of many brain disorders such as brain edema and Neuromyelitis optica. In addition to these diseases, there is growing attention to the involvement of AQPs in the removal of waste products in Alzheimer's disease (AD). This indicates that targeting fluid homeostasis is a novel and attractive approach for AD. This review article aims to summarize recent knowledge on the pathological implications of AQPs in AD, discussing unsolved questions and future prospects.

Thorium impact on tobacco root transcriptome

Thorium is natural actinide metal with potential use in nuclear energetics. Contamination by thorium, originated from mining activities or spills, represents environmental risk due to its radioactivity and chemical toxicity. A promising approach for cleaning of contaminated areas is phytoremediation, which need to be based, however, on detail understanding of the thorium effects on plants. In this study we investigated transcriptomic response of tobacco roots exposed to 200μM thorium for one week. Thorium application resulted in up-regulation of 152 and down-regulation of 100 genes (p-value <0.01, fold change ≥2). The stimulated genes were involved in components of jasmonic acid and salicylic acid signaling pathways and various abiotic (e.g. oxidative stress) and biotic stress (e.g. pathogens, wounding) responsive genes. Further, up-regulation of phosphate starvation genes and down-regulation of genes involved in phytic acid biosynthesis indicated that thorium disturbed phosphate uptake or signaling. Also expression of iron responsive genes was influenced. Negative regulation of several aquaporins indicated disturbance of water homeostasis. Genes potentially involved in thorium transport could be zinc-induced facilitator ZIF2, plant cadmium resistance PCR2, and ABC transporter ABCG40. This study provides the first insight at the processes in plants exposed to thorium.

Astroglial Redistribution of Aquaporin 4 During Spongy Degeneration in a Canavan Disease Mouse Model

Canavan disease is a spongiform leukodystrophy caused by an autosomal recessive mutation in the aspartoacylase gene. Deficiency of oligodendroglial aspartoacylase activity and a subsequent increase of its substrate N-acetylaspartate are the etiologic factors for the disease. N-acetylaspartate acts as a molecular water pump. Therefore, an osmotic-hydrostatic mechanism is thought to be involved in the development of the Canavan disease phenotype. Astrocytes express water transporters and are critically involved in regulating and maintaining water homeostasis in the brain. We used the ASPA(Nur7/Nur7) mouse model of Canavan disease to investigate whether a disturbance of water homeostasis might be involved in the disease's progression. Animals showed an age-dependent impairment of motor performance and spongy degeneration in various brain regions, among the basal ganglia, brain stem, and cerebellar white matter. Astrocyte activation was prominent in regions which displayed less tissue damage, such as the corpus callosum, cortex, mesencephalon, and stratum Purkinje of cerebellar lobe IV. Immunohistochemistry revealed alterations in the cellular distribution of the water channel aquaporin 4 in astrocytes of ASPA(Nur7/Nur7) mice. In control animals, aquaporin 4 was located exclusively in the astrocytic end feet. In contrast, in ASPA(Nur7/Nur7) mice, aquaporin 4 was located throughout the cytoplasm. These results indicate that astroglial regulation of water homeostasis might be involved in the partial prevention of spongy degeneration. These observations highlight aquaporin 4 as a potential therapeutic target for Canavan disease.

Copeptin as a Diagnostic Marker in the Management of Neurosurgical Patients with Disturbance of Water Homeostasis

Copeptin as a Diagnostic Marker in the Management of Neurosurgical Patients with Disturbance of Water Homeostasis

Urinary aquaporin‐2 excretion during ibuprofen or indomethacin treatment in preterm infants with patent ductus arteriosus

Water channel AQP2 is the target for vasopressin (AVP) and a major determinant of urinary concentrating capacity. In mature kidneys, prostaglandins counteract the effect of AVP on AQP2 expression at functional sites. We investigated whether disturbances in water homeostasis in infants with patent ductus arteriosus (PDA) treated with prostaglandin inhibitors can be attributed to activation of AQP2. In 53 infants with symptomatic PDA (gestational age 24-33 weeks), 30 receiving ibuprofen and 23 indomethacin starting at 2-15 days of life, clinical and biochemical data were collected before treatment and after each dose of the drugs. Urinary AQP2 was determined by dot immunoblotting. Urinary AQP2 level and osmolality were decreased in both groups. Urinary osmolality was overall low and correlated inversely with fluid uptake. In ibuprofen group, there was no correlation of AQP2 level with urinary osmolality. There was no AQP2 upregulation in the infants. The low urinary osmolality and dissociation between urinary osmolality and urinary AQP2 level indicate that the fluid retention sometimes observed in PDA infants treated with prostaglandin inhibitors is not caused by increased levels of functional AQP2. Thus, knowledge about the renal physiology of the adult cannot always be transferred to the infant kidney.

Water Channels (Aquaporins) and Their Role for Postnatal Adaptation

Birth is a transition from an underwater life in the uterus to a terrestrial life in a milieu where supply of water is limited. Rapid adaptation to the new environment is crucial for survival and health of infants. The discovery of a family of molecules-aquaporin (AQP) water channels-that are responsible for regulated water transport across cell membranes has made it possible to identify the molecular mechanisms behind the postnatal homeostatic adaptation and to better understand water imbalance-related disorders in infancy and childhood. Thirteen mammalian AQP isoforms have been identified, most of them having a unique tissue-specific pattern of expression. Most mammalian AQPs can be dynamically regulated, which makes them potential targets for the development of new drugs for diseases associated with disturbances in water homeostasis. This review deals with AQP in kidney, lung, and brain. Evidence is presented that AQPs are expressed in a specific age-dependent manner and that the timed expression of AQPs may have a crucial role during the early postnatal period.

Renal water handling in rats with decompensated liver cirrhosis.

The present study was performed to investigate the renal handling of water in rats with decompensated liver cirrhosis. Liver cirrhosis was induced by intraperitoneal administration of carbon tetrachloride twice weekly for 16 wk. Control rats were treated with vehicle. The cirrhotic rats developed severe disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentration and ascites, and the ability to excrete an intravenous water load was significantly impaired. Plasma concentrations of vasopressin and aldosterone were increased. Mean arterial pressure, glomerular filtration rate (GFR), and fractional lithium excretion were decreased. Acute vasopressin type 2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg. kg(-1). h(-1)) was performed during conditions whereby volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. The aquaretic response to OPC-31260 was similar in cirrhotic and control rats. However, the OPC 31260-induced rises in fractional water excretion (delta V/GFR; +24%) and fractional distal water excretion (delta V/C(Li); +46%) were significantly increased in the cirrhotic rats, where V is flow rate and delta is change. This suggests that vasopressin-mediated renal water reabsorption capacity was increased in the cirrhotic rats. Semiquantitative immunoblotting revealed that the expression of the vasopressin-regulated water channel aquaporin-2 was unchanged in membrane fractions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duct water reabsorption in rats with decompensated liver cirrhosis.

Water Channels in Renal and Nonrenal Tissues

A family of structurally similar channel-forming membrane glycoproteins, termed water channels or aquaporins, accounts for the constitutive as well as vasopressin-regulated water permeability in respective epithelia. Heterogeneity of aquaporins provides a molecular basis for some genetic diseases and treatment of certain diseases with disturbances in water homeostasis.

Water transport in renal tubules is mediated by aquaporins.

Water reabsorption in mammalian renal tubules is mediated by channel-forming membrane glycoproteins termed aquaporins (AQP). So far three different kinds of AQP have been described in renal tubules. AQP CHIP is localized to the luminal and contraluminal membranes of the proximal tubule and descending thin limb cells, i.e., in tubule segments that exhibit a constitutive high permeability to water that is insensitive to vasopressin. AQP-CD is present in subapical vesicles and the luminal membrane of collecting duct principal cells. Its intracellular distribution depends on vasopressin or hydration status of the animal and, thus, may represent the vasopressin-sensitive water channel. The basolateral integral protein (BLIP) may represent the vasopressin-insensitive water channel in basolateral membrane of collecting duct principal cells. The exact localization of a recently cloned homologue, WCH3, which may be either related to BLIP or represent yet another kind of AQP, is not known. Heterogeneity of aquaporins in the renal tubule may provide a molecular basis for the treatment of certain diseases with disturbances in water homeostasis.

The relationship between plasma osmolality and plasma vasopressin concentration is altered in old male Lewis rats.

Kidney dysfunction has been observed in aged humans and rats, the primary cause of which may reside in the kidney itself or in the hypothalamus. The latter possibility is suggested by the increased release of AVP in response to salt infusion in humans. The effect of age on the relationship between plasma osmolality and plasma AVP concentration has never been verified in an animal model. Therefore, in the present study, 9% salt solution was infused into adult and aged Lewis rats, and plasma AVP concentration and osmolality were measured. Basal plasma AVP concentration, osmolality and total water intake were not altered in aged Lewis rats as compared with adult animals, indicating the absence of overt disturbances in water homeostasis. Infusion of 9% salt solution resulted in a linear increase in plasma osmolality in both adult and aged rats. Plasma osmolality increased more with time in aged animals than in adult animals, suggesting an age-related difference in kidney function during salt infusion. Plasma AVP concentration increased 50% less with osmolality at relatively low osmolalities, but not at relatively high osmolalities. The altered relationship between plasma osmolality and plasma AVP concentration in rats with age may be related to changes in neurons monitoring osmolality or to changes in baroreflex regulation. The data suggest that reduced kidney function with age does not result from an altered relationship between plasma osmolality and plasma AVP concentration.

Elevated angiotensin-converting enzyme (kininase II) in the cerebrospinal fluid of neuroleptic-treated schizophrenic patients

Disturbances of water homeostasis have frequently been reported in schizophrenia. Water homeostasis is regulated by arginine vasopressin (AVP), the renin-angiotensin system and natriuretic hormones. The aim of this study was to determine the activity of the central renin-angiotensin system in schizophrenia by measuring levels of angiotensin-converting enzyme (ACE) in the cerebrospinal fluid (CSF) and blood in 14 in-patients with schizophrenia on neuroleptic medication and in 9 healthy volunteers. The levels of CSF ACE were significantly higher in the schizophrenia group. There were no correlations between CSF ACE and gender, age, age at first episode, duration of illness, term of hospitalization or neuroleptic dosage. No correlations between CSF ACE and serum ACE were found in either group. The authors suggest an activated central renin-angiotensin system in schizophrenia at least during antipsychotic drug treatment, which may cause ‘psychogenic’ polydipsia in some patients. ACE and the brain renin-angiotensin system may also play a role in the regulation of neuron growth and differentiation in schizophrenia.

Disturbances of thirst and water homeostasis in patients with affective illness

Three patients with recurrent affective disorders experienced polydipsia and the syndrome of inappropriate secretion of antidiuretic hormone in association with acute exacerbations of their affective disorders. These disturbances of water homeostasis responded to treatment of the affective disorders.