ATPase In Brain Research Articles

A study on membrane enzyme Na+-K+-ATPase in lindane exposed fish, Channa punctatus

Na+-K+-ATPase is a membrane-bound enzyme responsible for the transport of ions through the membrane and the immediate release of energy. This enzyme is known to be an early target for oxygen radical-induced damage to intact cells. Exposure of C. punctatus to subacute concentrations of lindane for 96 h caused a significant reduction in the activities of Na+-K+-ATPase in all the tissues of the fish tested, with the brain being maximally affected and the heart being the least affected organ at the highest concentration of lindane (0.1 mg/L). The effect of pesticides was concentration-dependent. The percent decrease in the activity of Na+-K+-ATPase in brain, gills, heart, kidney, liver, and muscle was found to be 36.7, 23.4, 19.2, 29, 22.9, and 29.7, respectively. The order of level of enzyme activity recorded was as follows: liver > gills > kidney > brain > muscle > heart in the control.

The role of Na+ -K+ -ATPase in the epileptic brain.

Na+‐K+‐ATPase, a P‐type ATP‐powered ion transporter on cell membrane, plays a vital role in cellular excitability. Cellular hyperexcitability, accompanied by hypersynchronous firing, is an important basis for seizures/epilepsy. An increasing number of studies point to a significant contribution of Na+‐K+‐ATPase to epilepsy, although discordant results exist. In this review, we comprehensively summarize the structure and physiological function of Na+‐K+‐ATPase in the central nervous system and critically evaluate the role of Na+‐K+‐ATPase in the epileptic brain. Importantly, we further provide perspectives on some possible research directions and discuss its potential as a therapeutic target for the treatment of epilepsy.

Oral Exposure to Tributyltin Induced Behavioral Abnormality and Oxidative Stress in the Eyes and Brains of Juvenile Japanese Medaka (Oryzias latipes).

The widely used compound tributyltin (TBT), which can be continuously detected in aquatic species and seafood, may induce diverse adverse effects on aquatic organisms. However, little is known regarding the mechanistic links between behavioral abnormality and oxidative stress in different fish tissues in response to oral TBT exposure. Herein, juvenile Japanese medaka (Oryzias latipes) were orally exposed to TBT at 1 and 10 ng/g-bw/d for four weeks. After exposure, the locomotor activity and social interaction of juvenile medaka were found to be significantly reduced in the 10 ng/g-bw/d TBT-exposed group. Furthermore, the antioxidant biomarkers in different tissues of juvenile medaka showed different levels of sensitivity to TBT exposure. The eye superoxide dismutase (SOD) activities markedly increased in both groups exposed to 1 and 10 ng/g-bw/d TBT, while the eye and brain malondialdehyde (MDA) levels increased in the higher dose group. Furthermore, the eye and brain ATPase activities markedly declined in the 1 ng/g-bw/d TBT-exposed group. A correlation analysis revealed that the decreased locomotor activity and social interaction in medaka were associated with the eye antioxidant enzyme (i.e., SOD and catalase (CAT)) activity and brain oxidative damage level. Thus, our findings suggested that there might be some mechanistic links between the behavioral abnormality induced by TBT exposure and oxidative stress in the eyes and brains of medaka. Thus, our findings indicate that the impacts of oral exposure to TBT should be considered to better assess its risk to the aquatic ecosystem and human health.

Effect of Autranellacongolensis on Lipid Profile of Rats’ Brain with Experimentally Induced Alzheimer’s Disease

Lipids are essentials components of the brain. Changes in brain lipid composition affect the physical and functional properties of the neuronal cell membrane and have been implicated in the physiopathology of Alzheimer disease (AD). We evaluated in this study the effect of hydroethanolicbark extract of A. Congolensis on lipid profile of rats’ brain with experimentally induced AD. The experimental model consisted of female rats, which received orally for 8 consecutive weeks a single dose of 50 mg/Kg b.w./day of aluminum trichloride (AlCl3) (except control group) followed by distilled water (disease control group) or doses of the extract (150 or 300 mg/Kg b.w./day) or vitamin E (100 mg/Kg b.w./day) or galanthamine (2 mg/Kg b.w. /day). Brain cholesterol, phospholipids and plasmalogenlevels and fluidity were evaluated. Brain membranes ATPase activities, Ca2+, Mg2+and glucose levels were also assayed. Significant modifications of brain lipid composition and fluidity were observed in disease control group compared with control. In addition, Na+, K+-ATPase and Mg2+-ATPase activities significantly decreased, the level of intracellular Ca2+ increased, Mg2+ content decreased and brain glucose level was significantly higher. Standard drugs (vitamin E,galanthamine) showed a negative effect on brain lipid profile. The extract of 150 mg showed significant improvements of brain lipid profile and fluidity. It also indicated improved brain ATPase activities, ions and glucose brain homeostasis. The extract (150 mg/Kg b.w. dose) by maintaining the brain lipid composition may protect neuronal cell membraneand probably preventing the progression of AD.

Modulation of rat synaptosomal ATPases and acetylcholinesterase activities induced by chronic exposure to the static magnetic field

Purpose: It is considered that exposure to static magnetic fields (SMF) may have both detrimental and therapeutic effect, but the mechanism of SMF influence on the living organisms is not well understood. Since the adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) are involved in both physiological and pathological processes, the modulation of Na+/K+-ATPase, ecto-ATPases and AChE activities, as well as oxidative stress responses were followed in synaptosomes isolated from rats after chronic exposure toward differently oriented SMF.Material and methods: Wistar albino rats were randomly divided into three experimental groups (six animals per group): Up and Down group - exposed to upward and downward oriented SMF, respectively, and Control group. After 50 days, the rats were sacrificed, and synaptosomes were isolated from the whole rat brain and used for testing the enzyme activities and oxidative stress parameters.Results: Chronic exposure to 1 mT SMF significantly increased ATPases, AChE activities, and malondialdehyde (MDA) level in both exposed groups, compared to control values. The significant decrease in synaptosomal catalase activity (1.48 ± 0.17 U/mg protein) induced by exposure to the downward oriented field, compared to those obtained for Control group (2.60 ± 0.29 U/mg protein), and Up group (2.72 ± 0.21 U/mg protein).Conclusions: It could be concluded that chronic exposure to differently oriented SMF increases ATPases and AChE activities in rat synaptosomes. Since brain ATPases and AChE have important roles in the pathogenesis of several neurological diseases, SMF influence on the activity of these enzymes may have potential therapeutic importance

Memory deficit, toxic effects and activity of Na(+), K(+)-ATPase and NTPDase in brain of Wistar rats submitted to orally treatment with alpha-terpinene.

The neurotoxic effects and activity of Na(+), K(+)-ATPase and NTPDase in Wistar rats after treatment with α-terpinene (daily oral administration of 0.5, 0.75 and 1.0mLkg(-1) for 10days) were examined. Results of the inhibitory avoidance task showed a memory deficit (p<0.05) in rats treated with all doses of α-terpinene. The evaluation of DNA damage in brain tissue revealed an increase (p<0.05) on frequency of damage and damage index in all concentrations. According to the cytotoxicity assay, doses of 0.5, 0.75 and 1.0mLkg(-1) increase the lactate dehydrogenase levels, and doses of 1.0mLkg(-1) also decrease (p<0.05) cell viability in brain cells. A decrease (p<0.05) on Na(+), K(+)-ATPase activity in brain tissue and on NTPDase activity in serum were observed in all concentrations of α-terpinene. These results suggest that the α-terpinene was cytotoxic and genotoxic to the brain cells by inducing loss of cell viability and DNA damage, as well as causing alterations in Na(+), K(+)-ATPase and NTPDase activity, what may contribute to the memory deficit of treated animals. Thus, α-terpinene cannot be consumed by the population at the doses studied.

Estimation of toxic hazard – A revised Cramer–Ford–Hall decision tree

Aluminium is neurotoxic in humans and has been implicated in several neurological disorders. Chronic use of buffered aspirins, as aspegic, would likely constitute the major human aluminium uptake source. Low-dose aspirin is beneficial in secondary prevention of cardiovascular events, so it is widely used for long periods of time. We studied if oral administration of aspegic to rats modified the aluminium inhibitory effect on brain (Na+/K+)ATPase due to alteration in synaptosomal membrane aluminium content. Adult male Wistar rats were submitted to sub-acute (1.00 g/day during 10 days) and chronic (0.03 g/day during 4 months) dietary AlCl3 exposure and/or to aspegic (0.11 g/day). The exposure protocol increased the synaptosomal aluminium content especially after a long-term exposure to aluminium and aspegic. Although no alterations were observed in rat body weight gain and adenylate energy charge, the (Na+/K+)ATPase activity was significantly reduced when aluminium was orally administered to rats. The oral administration of aspegic increased the synaptosomal aluminium content and concomitantly enhanced the (Na+/K+)ATPase inhibition. In our exposure protocol the increase in synaptosomal aluminium content correlates with the reduction of the (Na+/K+)ATPase activity.

Potential protection of taurine on antioxidant system and ATPase in brain and blood of rats exposed to aluminum.

Taurine (Tau) is used in clinical treatments but its protection of brains against aluminum-induced oxidative damage has been explored for the first time. The positive effect of Tau was studied on the activities of antioxidant enzymes and ATPase. Aluminum (Al) intake caused significant increasement of malondialdehyde (MDA) but reduction of the activities of superoxide dismutase, glutathione peroxidase (GSH-Px), Na(+)K(+)-ATPase and Mg(2+)-ATPase in brain compared to control group (P < 0.05). Tau administration, however, significantly reduced the MDA content, and increased the activities of aforementioned enzymes (P < 0.05). The MDA content was higher and the activities of GSH-Px, Ca(2+)-ATPase and Mg(2+)-ATPase lower in the blood of the Al-treated group' (P < 0.05), while Tau markedly decreased MDA content and improved the activities of GSH-Px and Ca(2+)-ATPase (P < 0.05). Tau may play a crucial role in the protection of antioxidant system and ATPase against Al-induced toxicity in brain and blood of rats.

Effect of lysine acetylsalicylate on aluminium accumulation and (Na+/K+)ATPase activity in rat brain cortex synaptosomes after aluminium ingestion

Aluminium is neurotoxic in humans and has been implicated in several neurological disorders. Chronic use of buffered aspirins, as aspegic, would likely constitute the major human aluminium uptake source. Low-dose aspirin is beneficial in secondary prevention of cardiovascular events, so it is widely used for long periods of time. We studied if oral administration of aspegic to rats modified the aluminium inhibitory effect on brain (Na+/K+)ATPase due to alteration in synaptosomal membrane aluminium content. Adult male Wistar rats were submitted to sub-acute (1.00g/day during 10 days) and chronic (0.03g/day during 4 months) dietary AlCl3 exposure and/or to aspegic (0.11g/day). The exposure protocol increased the synaptosomal aluminium content especially after a long-term exposure to aluminium and aspegic. Although no alterations were observed in rat body weight gain and adenylate energy charge, the (Na+/K+)ATPase activity was significantly reduced when aluminium was orally administered to rats. The oral administration of aspegic increased the synaptosomal aluminium content and concomitantly enhanced the (Na+/K+)ATPase inhibition. In our exposure protocol the increase in synaptosomal aluminium content correlates with the reduction of the (Na+/K+)ATPase activity.

Delayed administration of zingerone mitigates the behavioral and histological alteration via repression of oxidative stress and intrinsic programmed cell death in focal transient ischemic rats

The neuronal mitochondria succumb to ischemia–reperfusion injury and release huge amount of reactive oxygen species and ultimately lead the neurons to intrinsic pathway of programmed cell death (iPCD). The present study was undertaken to elucidate the ischemia–reperfusion-induced oxidative stress and molecular events in iPCD 24h post ischemia–reperfusion injury and plausible mitigation by zingerone, a potent antioxidant of ginger rhizome. The right middle cerebral artery was occluded for 2h followed by reperfusion for 22hours. A maximum infarct volume (43.29%) and mitochondrial injury (56.99%) was observed in middle cerebral artery occlusion (MCAO) group. However, zingerone administration (50 and 100mg/kg b.wt. orally twice) at 5h and 12h from initiation of MCAO showed a significant reduction in infarct volume and mitochondrial injury (p<0.001). Zingerone treatment significantly improved behavioral outputs (p<0.05) and histological architecture (p<0.001) by reducing lipid peroxidation (p<0.01), augmenting the reduced glutathione content (p<0.01) and restoring Na+-K+ ATPase and superoxide dismutase activities (p<0.01) in MCAO brain. Zingerone successfully reduced the caspase-3 and -9 activities in MCAO group (p<0.05) and succeeded in lowering the expressions of pro-apoptotic proteins — Apaf-1 and Bax (p<0.001). The present study suggests that zingerone is a potent antioxidant that salvaged the ischemic penumbral zone neurons by inhibiting iPCD and oxidative stress.

Alteration of aluminium inhibition of synaptosomal (Na+/K+)ATPase by colestipol administration

The ability of aluminium to inhibit the (Na+/K+)ATPase activity has been observed by several authors. During chronic dietary exposure to AlCl3, brain (Na+/K+)ATPase activity drops, even if no alterations of catalytic subunit protein expression and of energy charge potential are observed. The aluminium effect on (Na+/K+)ATPase activity seems to implicate the reduction of interacting protomers within the oligomeric ensemble of the membrane-bound (Na+/K+)ATPase. The activity of (Na+/K+)ATPase is altered by the microviscosity of lipid environment. We studied if aluminium inhibitory effect on (Na+/K+)ATPase is modified by alterations in synaptosomal membrane cholesterol content. Adult male Wistar rats were submitted to chronic dietary AlCl3 exposure (0.03g/day of AlCl3) and/or to colestipol, a hypolidaemic drug (0.31g/day) during 4months. The activity of (Na+/K+)ATPase was studied in brain cortex synaptosomes with different cholesterol contents. Additionally, we incubate synaptosomes with methyl-β-cyclodextrin for both enrichment and depletion of membrane cholesterol content, with or without 300μM AlCl3. This enzyme activity was significantly reduced by micromolar AlCl3 added in vitro and when aluminium was orally administered to rats. The oral administration of colestipol reduced the cholesterol content and concomitantly inhibited the (Na+/K+)ATPase. The aluminium inhibitory effect on synaptosomal (Na+/K+)ATPase was reduced by cholesterol depletion both in vitro and in vivo.

Localization of Na+/K+-ATPase in silkworm brain: A possible mechanism for protection of Na+/K+-ATPase from Ca2+

In mammalian blood, the Na+ concentration is higher than the K+ concentration, whereas in hemolymph of lepidopterous insects, the K+ concentration is higher than the Na+ concentration. Na+/K+-ATPase regulates Na+ and K+ concentrations in mammalian blood. Therefore, the absence of Na+/K+-ATPase in lepidopterous insects might be expected. However, we have observed that Na+/K+-ATPase is abundant in nerve tissues of larvae of silkworm, a lepidopterous insect. Furthermore, we found that silkworm Na+/K+-ATPase was completely inhibited by 3mM Ca2+in vitro (Homareda, 2010), although the Ca2+ concentration is very high (30–50mM) in the hemolymph of silkworm larvae. To investigate the reason why silkworm Na+/K+-ATPase is not inhibited by Ca2+in vivo, we observed the localization of Na+/K+-ATPase in nerve tissues using immunohistochemical techniques. Na+/K+-ATPase was distributed in the cortex and neuropile but not in the perineurium of the silkworm brain, while plasma membrane Ca2+-ATPase appeared to distribute in the perineurium as well as in the cortex and neuropile. These results support a possibility that neuronal Na+/K+-ATPase is protected from a high Ca2+ concentration by the blood–brain barrier consisting of perineurial glial cells with plasma membrane Ca2+-ATPase.

Effect of Nicotine on ATPase, Catalase and Calcium Levels in the Presence of Oligoelements in Brain Regions of Young Rats

The effect of nicotine on membrane alterations and fluidity changes in very young models remains unclear. The aim of this study was to evaluate the effect of nicotine on total ATPase, H(2)O(2) and calcium in brain of young rats in the presence of oligoelements. Male Wistar rats (weight 80 g) received intraperitoneally either a single dose or repeated doses for 4 days as follows: Group 1 (control) NaCl 0.9%; group 2 nicotine (1mg/kg); group 3 oligoelements (50 μl); and group 4 nicotine (1mg/kg) + oligoelements (50 μl). The brain regions (cortex, hemispheres and cerebellum + medulla oblongata) of each rat were then obtained to measure the concentrations of total ATPase, H(2)O(2) and calcium using spectrophotometric methods. Total ATPase increased significantly (p < 0.05) in groups treated with oligoelements in repeated doses in hemisphere region, and in groups that received oligoelements + nicotine in single or repeated doses in medulla oblongata. Catalase showed significant decreased in cerebellum/medulla oblongata. Results suggest that nicotine induces changes in membrane fluidity in brain of young rats, and that ATPase could be a biomarker of nicotine consumption in young subjects.

Marked reduction of Na+, K+-ATPase and creatine kinase activities induced by acute lysine administration in glutaryl-CoA dehydrogenase deficient mice

Glutaric acidemia type I (GA I) is an inherited neurometabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase activity leading to accumulation of predominantly glutaric (GA) and 3-hydroxyglutaric (3HGA) acids in the brain and other tissues. Affected patients usually present with hypotonia and brain damage and acute encephalopathic episodes whose pathophysiology is not yet fully established. In this study we investigated important parameters of cellular bioenergetics in brain, heart and skeletal muscle from 15-day-old glutaryl-CoA dehydrogenase deficient mice (Gcdh−/−) submitted to a single intra-peritoneal injection of saline (Sal) or lysine (Lys — 8μmol/g) as compared to wild type (WT) mice. We evaluated the activities of the respiratory chain complexes II, II-III and IV, α-ketoglutarate dehydrogenase (α-KGDH), creatine kinase (CK) and synaptic Na+, K+-ATPase. No differences of all evaluated parameters were detected in the Gcdh−/− relatively to the WT mice injected at baseline (Sal). Furthermore, mild increases of the activities of some respiratory chain complexes (II-III and IV) were observed in heart and skeletal muscle of Gcdh−/− and WT mice after Lys administration. However, the most marked effects provoked by Lys administration were marked decreases of the activities of Na+, K+-ATPase in brain and CK in brain and skeletal muscle of Gcdh−/− mice. In contrast, brain α-KGDH activity was not altered in WT and Gcdh−/− injected with Sal or Lys. Our results demonstrate that reduction of Na+, K+-ATPase and CK activities may play an important role in the pathogenesis of the neurodegenerative changes in GA I.

Repeated Oral Dose Toxicity of Iron Oxide Nanoparticles: Biochemical and Histopathological Alterations in Different Tissues of Rats

Iron oxide (Fe2O3) nanoparticles are widely used in different fields of nanotechnology. However, studies on its toxicological effects in humans and the environment are scarce. Therefore in this investigation 28 days repeated dose oral toxicity studies were conducted on Fe2O3-30 nanoparticles and its counterpart Fe2O3-Bulk with special reference to target biochemical enzymes and histopathological changes in different tissues of female albino Wistar rats. The alterations observed after Fe2O3-30 treatment in various tissues of exposed rats were dose dependent. Low dose was less effective than medium and high doses with low dose demonstrating "no observed adverse effect" (NOAEL). Further, high dose treated rats showed toxic sign and symptoms but no mortality. Due to the repeated doses of Fe2O3-30 nanoparticles, significant inhibition was observed in total, Na(+)-K+, Mg2+ and Ca(2+)-ATPases in brain of exposed rats. Similarly, significant inhibition was recorded in RBC and brain acetylcholinesterase indicating that both synaptic transmission and nerve conduction were affected by this compound. Fe2O3-30 significantly increased aspartate amino transferase, alanine amino transferase and lactate dehydrogenase in serum and liver, whereas, these enzymes were significantly decreased in kidney indicating tissue necrosis and possible leakage of these enzymes into the blood stream. Increased levels of these enzymes in liver as well as in serum might be an adaptive mechanism due to the stress of iron nanoparticles. High dose treated rats of Fe2O3-30 showed dilated central vein, perivascular round cell collections in liver along with focal areas of necrosis, whereas kidney showed focal tubular damage and red pulp congestion, whereas prominent white pulp indices were observed in spleen. However, histopathological analysis of heart and brain tissues failed to show any adverse changes in their architecture exposed to repeated doses of Fe2O3-30 when compared with controls. Fe2O3-Bulk did not induce any adverse effects in either biochemical parameters or histopathology in the treated rats and the changes observed were near to controls and mostly insignificant, indicating that the counter part of nanoparticles i.e., bulk material is less potent than the nanoparticles in causing toxicity in the exposed animals. These results suggested that as particle size decreases, this iron nanoparticle showed increased toxicity, even though the same material is relatively inert in bulk form. The changes observed in these target enzyme activities could be useful as biomarkers of exposure to nanoparticles.

Effects of TCDD on Na+ K+ AtPase and Ca2+ ATPase in brain of mice

目的 研究2,3,7,8-四氯二苯并二噁英(TCDD)对小鼠脑组织中Na+-K+-ATP酶、Ca2+-ATP酶活力的影响.方法 将48只雌雄各半的昆明种小鼠按性别随机分为高、中、低剂量TCDD染毒组和对照组,每组雌雄各6只,TCDD染毒剂量分别为100、10、1 μg/kg,用腹腔注射的方式一次染毒,48 h后,测定脑组织中Na+-K+-ATP酶、Ca2+-ArrP酶活力.结果 雌性低剂量、中剂量染毒组和雄性高剂量染毒组小鼠脑组织中Na+-K+-ATP酶活力[分别为(17.35±3.07)、(16.13±2.42)、(20.25±2.72)μmolPi·mg pro-1·h-1]明显升高,与对照组[分别为(13.60±1.72)、(15.97±1.90) μmol Pi·mg pro-1·h-1相比,差异均有统计学意义(P 0.05).结论 TCDD急性染毒能提高小鼠脑组织中Na+-K+-ATP酶的活力,且存在性别差异。

Inhibition of lindane-induced toxicity using alpha-lipoic acid and vitamin E in the brain of Mus musculus

In the present investigation, we have used adenosine triphosphatase (ATPase) activity as biochemical test of toxic action of lindane that was explained by lipid peroxidation model. Study was also undertaken to ascertain the potential protective role of alpha-lipoic acid (ALA) and vitamin E on the same parameters. Highly acute dose of lindane, i.e., 40 mg/kg bw for 18 h exposure, was used for creating lesions in brain. Lipid peroxidation was measured in terms of glutathione peroxidase and thio barbituric acid-reacting substances (TBARS). Various brain regions under investigation were cerebellum and pons-medulla oblongata. Healthy, male, Swiss mice (7-8 weeks old) were allocated into four groups. First group was control, second group was treated with lindane, third group was treated purely with antioxidants, and fourth group received both antioxidants and lindane treatment. Results revealed the significant difference (at 1% and 5% in all groups) in all studied parameters from control. Increased TBARS level in second group suggests that lindane enhances the production of free radicals in studied brain regions. Antioxidants under test are efficient remedy for neurotoxicity caused by lindane. We conclude that lindane manifests toxic effects on brain ATPase and enhances lipid peroxidation. ALA and vitamin E in combination may provide protection against lindane-induced acute toxicity.

The antiepileptic effect of Centella asiatica on the activities of Na/K, Mg and Ca-ATPases in rat brain during pentylenetetrazol-induced epilepsy.

Background:To study the anticonvulsant effect of different extracts of Centella asiatica (CA) in male albino rats with reference to Na+/K+, Mg2+ and Ca2+-ATPase activities.Materials and Methods:Male Wistar rats (150±25 g b.w.) were divided into seven groups of six each i.e. (a) control rats treated with saline, (b) pentylenetetrazol (PTZ)-induced epileptic group (60 mg/kg, i.p.), (c) epileptic group pretreated with n-hexane extract (n-HE), (d) epileptic group pretreated with chloroform extract (CE), (e) epileptic group pretreated with ethyl acetate extract (EAE), (f) epileptic group pretreated with n-butanol extract (n-BE), and (g) epileptic group pretreated with aqueous extract (AE).Results:The activities of three ATPases were decreased in different regions of brain during PTZ-induced epilepsy and were increased in epileptic rats pretreated with different extracts of CA except AE.Conclusion:The extracts of C. asiatica, except AE, possess anticonvulsant and neuroprotective activity and thus can be used for effective management in treatment of epileptic seizures.

Ontogeny of ATP hydrolysis and isoform expression of the Plasma Membrane Ca2+-ATPase in mouse brain

BackgroundPlasma membrane Ca2+-ATPases (PMCAs) are high affinity Ca2+ transporters actively involved in intracellular Ca2+ homeostasis. Considering the critical role of Ca2+ signalling in neuronal development and plasticity, we have analyzed PMCA-mediated Ca2+-ATPase activity and PMCA-isoform content in membranes from mouse cortex, hippocampus and cerebellum during postnatal development.ResultsPMCA activity was detected from birth, with a faster evolution in cortex than in hippocampus and cerebellum. Western blots revealed the presence of the four isoforms in all regions, with similar increase in their expression patterns as those seen for the activity profile. Immunohistochemistry assays in cortex and hippocampus showed co-expression of all isoforms in the neuropil associated with synapses and in the plasma membrane of pyramidal cells soma, while cerebellum showed a more isoform-specific distribution pattern in Purkinje cells.ConclusionThese results show an upregulation of PMCA activity and PMCA isoforms expression during brain development in mouse, with specific localizations mainly in cerebellum. Overall, our findings support a close relationship between the ontogeny of PMCA isoforms and specific requirements of Ca2+ during development of different brain areas.

L-Cysteine’s Effect on Modulated Rat Brain Enzymes with Forced Swimming

Forced exercise is associated with oxidative stress, and L-cysteine (L-cys) administration reduces free-radical production. To investigate whether L-cys (5 mg/kg) intraperitoneal administration can ameliorate modulated total antioxidant status (TAS), protein concentration, and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase, and Mg2+-ATPase in rat brain after 2 and 3 hr of forced swimming. TAS, protein, and enzyme activities were measured spectrophotometrically before and after 2 and 3 hr of exercise without or with L-cys administration. TAS concentration (55.6 +/- 1.5 vs. 42.1 +/- 1.0 vs. 37.4 +/- 1.2 micromol/L, p < .001), protein concentration (5.68 +/- 0.36 vs. 5.40 +/- 0.18 vs. 4.01 +/- 0.16 mg/ml, p < .01), and AChE activity (0.89 +/- 0.05 vs. 0.61 +/- 0.04 vs. 0.48 +/- 0.03 DeltaOD/min x mg protein, p < .001) were significantly reduced, whereas Na+,K+-ATPase (6.00 +/- 0.36 vs. 10.44 +/- 1.04 vs. 11.90 +/- 1.21 micromol phosphorus inorganic/hr x mg protein, p < .001) and Mg2+-ATPase activity (7.20 +/- 0.65 vs. 10.88 +/- 1.08 vs. 11.55 +/- 1.22 mmol phosphorus inorganic/hr x mg protein, p < .001) were statistically significantly increased after 2 and 3 hr of forced exercise. Post-L-cys administration, AChE activity was decreased (0.90 +/- 0.04 vs. 0.47 +/- 0.02 DeltaOD/min x mg protein, p < .001) and remained unaltered (0.64 +/- 0.04 vs. 0.67 +/- 0.04 DeltaOD/min x mg protein, p > .05) 2 and 3 hr postexercise (0.47 +/- 0.02 vs. 0.54 +/- 0.02 DeltaOD/min x mg protein, p > .05). Na+,K+-ATPase was decreased and remained unchanged (1.85 +/- 0.17 vs. 1.77 +/- 0.19 mumol phosphorus inorganic/hr x mg protein, p > .05) 2 and 3 hr postswimming (1.91 +/- 0.19 vs. 2.06 +/- 0.17 mumol phosphorus inorganic/hr x mg protein, p > .05). Mg2+-ATPase activity was similar with L-cys supplementation pre- vs. postswimming. L-cys administration might ameliorate modulated rat brain enzyme activities induced by free-radical production during forced swimming.