The role of folate metabolism-related gene polymorphisms in the development of meningiomas

Meningiomas are (usually) slow-growing benign tumors, and several factors have been implicated in their development. Increasing age, previous exposure to ionizing radiation, endogenous hormone status and history, hormone replacement therapy, genetic variants and polymorphisms are the main factors that have been proven or assumed to be involved in meningioma formation. The complex genetic background supporting the pathogenesis of meningiomas includes a large number of mutations and polymorphisms that might be actively involved in tumor development, progression and recurrence. The aim of this mini-review is to summarize the current data concerning the role of folate metabolism-related gene polymorphisms in the development of meningiomas

The neuroprotective role of L-cysteine towards the effects of short-term exposure to lanthanum on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase

Lanthanum (La) is a rare earth element that is widely used for industrial, medical and agricultural purposes. Its neurotoxic effects are linked to its physical and chemical properties and its interaction with certain trace elements and membrane-bound enzymes. The aim of this study was to investigate the effects of short-term La-administration (as LaCl(3), 53 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase, as well as the potential effect of the co-administration of the antioxidant L: -cysteine (Cys, 7 mg/kg) on the above parameters. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (La), C (Cys),and D (La and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above mentioned parameters were measured spectrophotometrically. Rats treated with La exhibited a significant reduction in brain TAS (-36%, P < 0.001, BvsA), that was partially limited by the co-administration of Cys (-13%, P < 0.01, DvsA), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both La (+23%, P < 0.001, BvsA) and Cys (+59%, P < 0.001, CvsA), while it was adjusted to control levels by the co-administration of La and Cys. The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by La-administration (-28%, P < 0.001, BvsA), while Cys supplementation could not reverse this decrease. The activity of Mg(2+)-ATPase exhibited a slight but statistically significant reduction due to La (-8%, P < 0.01, BvsA), that was further reduced by Cys co-administration (-25%, P < 0.001, DvsA). The above findings suggest that La short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed into control levels by Cys co-administration, which could thus be considered for future applications as a neuroprotective agent against chronic exposure to La. The activities of Na(+),K(+)- and Mg(2+)-ATPase that were inhibited by La, could not be reversed by Cys co-administration. A role for the already reported concentration-dependent interaction of La with Ca-binding sites (such as Ca(2+)-ATPase) might be considered for certain of the above phenomena

Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats

Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (-11% vs Control, p < 0.01) and CD+TAA administration (-19% vs Control, p < 0.001), but was not significantly altered due to TAA administration. The rat brain AChE activity was found significantly increased by TAA administration (+11% vs Control, p < 0.01), as well as by CD+TAA administration (+14% vs Control, p < 0.01). However, AChE was not found to be significantly altered by the 30-day dietary CD. On the other hand, CD caused a significant increase in brain Na(+),K(+)-ATPase activity (+16% vs Control, p < 0.05) and had no significant effect on Mg(2+)-ATPase. Exposure to TAA had no significant effect on Na(+),K(+)-ATPase, but inhibited Mg(2+)-ATPase (-20% vs Control, p < 0.05). When administered to CD rats, TAA caused a significant decrease in Na(+),K(+)-ATPase activity (-41% vs Control, p < 0.001), but Mg(2+)-ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na(+),K(+)-ATPase, but caused a dramatic decrease in its activity (-41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na(+),K(+)-ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission)

Short-term exposure to nickel alters the adult rat brain antioxidant status and the activities of crucial membrane-bound enzymes: neuroprotection by L-cysteine

Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation) and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of short-term Ni-administration (as NiCl(2), 13 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase, and Mg(2+)-ATPase; in addition, the potential effect of the co-administration of the antioxidant L-cysteine (Cys, 7 mg/kg) on the above parameters was studied. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Ni), C (Cys), and D (Ni and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above-mentioned parameters were measured spectrophotometrically. Rats treated with Ni exhibited a significant reduction in brain TAS (-47%, p < 0.001, BvsA) that was efficiently limited by the co-administration of Cys (-4%, p > 0.05, DvsA; +83%, p < 0.001, DvsB), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Ni (+30%, p < 0.001, BvsA) and Cys (+62%, p < 0.001, CvsA), while it tended to adjust to control levels by the co-administration of Ni and Cys (+13%, p < 0.001, DvsA; -13%, p < 0.001, DvsB). The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by Ni-administration (-49%, p < 0.001, BvsA), while Cys supplementation could not reverse this decrease (-44%, p < 0.001, DvsA). The activity of Mg(2+)-ATPase was not affected by Ni-administration (-3%, p > 0.05, BvsA), but was significantly reduced when combined with Cys administration (-17%, p < 0.001, DvsA). The above findings suggest that Ni short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed to control levels by Cys co-administration; Cys could thus be considered (for future applications) as a potential neuroprotective agent against chronic exposure to Ni. The activity of Na(+),K(+)-ATPase that was inhibited by Ni, could not be reversed by Cys co-administration. The matter requires further investigation in order to fully elucidate the spectrum of the neurotoxic effects of Ni

Effects of adult-onset choline deprivation on the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase in crucial rat brain regions.

Choline (Ch) plays an important role in brain neurotransmission, while Ch-deprivation (CD) has been linked to various pathophysiological states. Prolonged ingestion of Ch-deficient diet (CDD) is known to produce CD causing a reduction of rat brain acetylcholine (ACh) levels, as well as memory and growth disorders. The aim of this study was to investigate the effect of a 2-month adult-onset CD on the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-ATPase in crucial brain regions of male rats. Adult rats were divided into two groups (control and CD). The CD group was fed with CDD for 2-months. At the end of the second month, rats were sacrificed by decapitation and the brain regions were rapidly removed. Enzyme activities were measured spectrophotometrically in the homogenated frontal cortex, hippocampus, hypothalamus, cerebellum, and pons. In CD rats, AChE activity was found statistically significantly increased in the hippocampus and the cerebellum (+28%, P<0.001 and +46%, P<0.001, respectively, as compared to control), while it was found unaltered in the other three regions (frontal cortex, hypothalamus and pons). (Na+,K+)-ATPase activity was found increased by CD in the frontal cortex (+30%, P<0.001), decreased in both hippocampus and hypothalamus (-68%, P<0.001 and -51%, P<0.001, respectively), and unaltered in both cerebellum and pons. No statistically significant changes were observed in the activities of Mg2+-ATPase in the frontal cortex and the hypothalamus, while statistically significant increases were recorded in the hippocampus (+21%, P<0.01), the cerebellum (+85%, P<0.001) and the pons (+19%, P<0.05), as compared to control levels. Our data suggest that adult-onset CD can have significant effects on the examined brain parameters in the examined crucial brain regions, as well as that CD is a metabolic disorder towards which different and brain region specific neurophysiological responses seem to occur. Following a 2-month adult-onset CD, the activity of AChE was found to be increased in the hippocampus and the cerebellum and unaltered in the other three regions (frontal cortex, hypothalamus and pons), while Na+,K+-ATPase activity was found to be increased in the frontal cortex, decreased in both hippocampus and hypothalamus, and unaltered in both cerebellum and pons. Moreover, Mg2+-ATPase activity was found to be unaltered in the frontal cortex and the hypothalamus, and increased in the hippocampus, the cerebellum and the pons. The observed differentially affected activities of AChE, (Na+,K+)-ATPase and Mg2+-ATPase (induced by CD) could result in modulations of cholinergic neurotransmission, neural excitability, metabolic energy production, Mg2+ homeostasis and protein synthesis (that might have a variety of neurophysiological consequences depending on the brain region in which they seem to occur)

Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na(+),K(+))- and Mg(2+)-ATPase: modulation by L-cysteine

Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L: -cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase. Thirty-eight male Wistar rats were divided into six groups: C(A) (8-week-control), C(B) (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), D(A) (8-week-diabetic), D(B) (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated). All diabetic rats were once treated with an intraperitoneal (i.p.) STZ injection (50 mg/kg body weight) at the beginning of the experiment, while all Cys-treated groups received i.p. injections of Cys 7 mg/kg body weight (daily, for 1-week, during the 9th-week). Whole rat brain parameters were measured spectrophotometrically. In vitro incubation with 0.83 mM of Cys or 10 mM of STZ for 3 h was performed on brain homogenate samples from groups C(B) and D(B), in order to study the enzymes' activities. Diabetic rats exhibited a statistically significant reduction in brain TAS (-28%, D(A) vs C(A);-30%, D(B) vs C(B)) that was reversed after 1-week-Cys-administration into basal levels. Diabetes caused a significant increase in AChE activity (+27%, D(A) vs C(A); +15%, D(B) vs C(B)), that was further enhanced by Cys-administration (+57%, D + Cys vs C(B)). The C + Cys group exhibited no significant difference compared to the C(B) group in TAS (+2%), but showed a significantly increased AChE activity (+66%, C + Cys vs C(B)). Diabetic rats exhibited a significant reduction in the activity of Na(+),K(+)-ATPase (-36%, D(A) vs C(A);-48%, D(B) vs C(B)) that was not reversed after 1-week Cys administration. However, in vitro incubation with Cys partially reversed the diabetes-induced Na(+),K(+)-ATPase inhibition. Mg(2+)-ATPase activity was not affected by STZ-induced diabetes, while Cys caused a significant inhibition of the enzyme, both in vivo (-14%, C + Cys vs C(B);-17%, D + Cys vs C(B)) and in vitro (-16%, D(B) + in vitro Cys vs C(B)). In vitro incubation with STZ had no effect on the studied enzymes. The present data revealed a protective role for Cys towards the oxidative effect of diabetes on the adult rat brain. Moreover, an increase in whole brain AChE activity due to diabetes was recorded (not repeatedly established in the literature, since contradictory findings exist), that was further increased by Cys. The inhibition of Na(+),K(+)-ATPase reflects a possible mechanism through which untreated diabetes could affect neuronal excitability, metabolic energy production and certain systems of neurotransmission. As concerns the use of Cys as a neuroprotective agent against diabetes, our in vitro findings could be indicative of a possible protective role of Cys under different in vivo experimental conditions