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Chronic Lithium Treatment (chronic + lithium_treatment)
Selected AbstractsHyperactivity, startle reactivity and cell-proliferation deficits are resistant to chronic lithium treatment in adult Nr2e1frc/frc miceGENES, BRAIN AND BEHAVIOR, Issue 7 2010B. K. Y. Wong The NR2E1 region on Chromosome 6q21-22 has been repeatedly linked to bipolar disorder (BP) and NR2E1 has been associated with BP, and more specifically bipolar I disorder (BPI). In addition, patient sequencing has shown an enrichment of rare candidate-regulatory variants. Interestingly, mice carrying either spontaneous (Nr2e1frc) or targeted (Tlx,) deletions of Nr2e1 (here collectively known as Nr2e1 -null) show similar neurological and behavioral anomalies, including hypoplasia of the cerebrum, reduced neural stem cell proliferation, extreme aggression and deficits in fear conditioning; these are the traits that have been observed in some patients with BP. Thus, NR2E1 is a positional and functional candidate for a role in BP. However, no Nr2e1 -null mice have been fully evaluated for behaviors used to model BP in rodents or pharmacological responses to drugs effective in treating BP symptoms. In this study we examine Nr2e1frc/frc mice, homozygous for the spontaneous deletion, for abnormalities in activity, learning and information processing, and cell proliferation; these are the phenotypes that are either affected in patients with BP or commonly assessed in rodent models of BP. The effect of lithium, a drug used to treat BP, was also evaluated for its ability to attenuate Nr2e1frc/frc behavioral and neural stem cell-proliferation phenotypes. We show for the first time that Nr2e1 -null mice exhibit extreme hyperactivity in the open field as early as postnatal day 18 and in the home cage, deficits in open-field habituation and passive avoidance, and surprisingly, an absence of acoustic startle. We observed a reduction in neural stem/progenitor cell proliferation in Nr2e1frc/frc mice, similar to that seen in other Nr2e1 -null strains. These behavioral and cell-proliferation phenotypes were resistant to chronic-adult-lithium treatment. Thus, Nr2e1frc/frc mice exhibit behavioral traits used to model BP in rodents, but our results do not support Nr2e1frc/frc mice as pharmacological models for BP. [source] Chronic lithium administration to FTDP-17 tau and GSK-3, overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revertJOURNAL OF NEUROCHEMISTRY, Issue 6 2006Tobias Engel Abstract Glycogen synthase kinase-3 (GSK-3) has been proposed as the main kinase able to aberrantly phosphorylate tau in Alzheimer's disease (AD) and related tauopathies, raising the possibility of designing novel therapeutic interventions for AD based on GSK-3 inhibition. Lithium, a widely used drug for affective disorders, inhibits GSK-3 at therapeutically relevant concentrations. Therefore, it was of great interest to test the possible protective effects of lithium in an AD animal model based on GSK-3 overexpression. We had previously generated a double transgenic model, overexpressing GSK-3, in a conditional manner, using the Tet-off system and tau protein carrying a triple FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) mutation. This transgenic line shows tau hyperphosphorylation in hippocampal neurones accompanied by neurofibrillary tangles (NFTs). We used this transgenic model to address two issues: first, whether chronic lithium treatment is able to prevent the formation of aberrant tau aggregates that result from the overexpression of FTDP-17 tau and GSK-3,; second, whether lithium is able to change back already formed NFTs in aged animals. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Furthermore, it is still possible to partially reverse tau pathology in advanced stages of the disease, although NFT-like structures cannot be changed. The same results were obtained after shut-down of GSK-3, overexpression, supporting the possibility that GSK-3 inhibition is not sufficient to reverse NFT-like aggregates. [source] A Bizarre Electrocardiographic Pattern Due to Chronic Lithium TherapyANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2010Mehmet Kayrak M.D. Cardiotoxicity that results from lithium overdose is uncommon and electrocardiographic (ECG) changes are rarely reported. However, some authors have specifically reported the occurrence of ischemic ECG changes due to a lithium overdose. This article describes a case that is demonstrating ECG changes that mimic inferior myocardial infarction during the course of chronic lithium treatment and showing QTc prolongation in this patient. The patients' ECG changes were partially recovered after hemodialysis. Ann Noninvasive Electrocardiol 2010;15(3):289,292 [source] Neuroprotective effect of chronic lithium treatment against hypoxia in specific brain regions with upregulation of cAMP response element binding protein and brain-derived neurotrophic factor but not nerve growth factor: comparison with acute lithium treatmentBIPOLAR DISORDERS, Issue 3 2008N Omata Objectives:, We evaluated the neuroprotective effect of chronically or acutely administered lithium against hypoxia in several brain regions. Furthermore, we investigated the contribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and cAMP response element binding protein (CREB) to the neuroprotective effect of lithium. Methods:, Brain slices were prepared from rats that had been treated chronically or acutely with lithium. The cerebral glucose metabolic rate (CMRglc) before and after hypoxia loading to brain slices was measured using the dynamic positron autoradiography technique with [18F]2-fluoro-2-deoxy- d -glucose. The changes of expression of proteins were investigated using Western blot analysis. Results:, Before hypoxia loading, the CMRglc did not differ between the lithium-treated and untreated groups. After hypoxia loading, the CMRglc of the untreated group was significantly lower than that before hypoxia loading. However, the CMRglc of the chronic lithium treatment group recovered in the frontal cortex, caudate putamen, hippocampus and cerebellum, but not in the thalamus. In contrast, the CMRglc of the acute lithium treatment group did not recover in any analyzed brain regions. After chronic lithium treatment, the levels of expression of BDNF and phospho-CREB were higher than those of untreated rats in the frontal cortex, but not in the thalamus. However, the expression of NGF did not change in the frontal cortex and thalamus. Conclusions:, These results demonstrated that lithium was neuroprotective against hypoxia only after chronic treatment and only in specific brain regions, and that CREB and BDNF might contribute to this effect. [source] Lithium isotopes: differential effects on renal function and histologyBIPOLAR DISORDERS, Issue 4 2001Peter M Stoll Objectives: Reduction in renal concentrating ability has been reported in patients undergoing chronic lithium treatment. Prior work has demonstrated differences in physiological effects of the stable lithium isotopes, 6Li and 7Li. Here, we measured the degree of polyuria, polydipsia and kidney histological changes induced in rats by equimolar amounts of 6LiCl, 7LiCl and the commercially available mixture of both isotopes. Methods: Rats were given 1.0 mEq/kg of either 6LiCl, 7LiCl or ,nLiCl' (isotope mixture, 93% 7LiCl) by subcutaneous injection twice daily for up to 49 days. Twenty-four-hour urine volume and water intake were measured daily. Kidneys from rats treated for 7 days with 1.5 mEq/kg 6LiCl, 7LiCl and vehicle were examined under light microscopy and histopathologic changes graded on a 4-point scale of severity. Results: All rats showed loss in renal concentrating ability manifested by increasing urine volume and water intake. Peak effects occurred after 9,13 days treatment, then declined to stable levels at two to three times pre-treatment level. Mean peak effect was significantly greater for 6LiCl than for 7LiCl. Chronic effects of 6LiCl (weeks 3,7 of treatment) on polyuria and polydipsia were persistently higher than that of 7LiCl. nLiCl effect was intermediate. Kidneys from rats treated for 7 days with 6LiCl showed more frequently severe lesions in renal tubules than did 7LiCl-treated rats. Conclusions: Our current data and prior studies suggest that elimination or reduction of 6Li from pharmaceutical preparations may merit further evaluation as a possibly less potentially nephrotoxic form of lithium treatment. [source] |