Regional and Subcellular Localization of Li+ and Other Cations in the Rat Brain Following Long‐Term Lithium Administration
- 5 October 1992
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 59 (4) , 1372-1380
- https://doi.org/10.1111/j.1471-4159.1992.tb08450.x
Abstract
Rats were given LiCl in their diet (40 mmol/kg dry weight) for at least 3 months to elucidate the regional and subcellular localization of Li+ in the brain as well as the effect of chronic lithium administration on the distribution of other cations. At steady-state the mean concentrations of Li+ were 0.66 mmol/kg wet weight in the whole brain and 0.52 mM in plasma. The tissue/plasma concentration ratio exceeded unity in all anatomical regions. No region showed excessive accumulation of Li+. Whole brain or regional contents of Na+ or K+ were unaffected by lithium treatment. Subcellular Li+ localization was demonstrated in nuclear, crude mitochondrial, and microsomal fractions of whole brain homogenate. Subfractionation of the crude mitochondrial fraction revealed energy-independent intrasynaptosomal and intramitochondrial Li+ and K+ localization at 0-4 degrees C. Li+ administered in vivo disappeared within 10 min from synaptosomes incubated at 37 degrees C. Li+ added in vitro at 1 mM attained a synaptosomal steady-state concentration within 30 min at 37 degrees C. In control rats, synaptosomal concentrations and synaptosomal/medium concentration gradients of cations paralleled their respective in vivo concentrations and gradients. Lithium treatment caused synaptosomal depletion of K+ and Mg2+ and hence probably partial membrane depolarization. Addition of 1 mM Li+ in vitro also caused synaptosomal Mg2+ depletion. The results indicate that Li+ is "accumulated" in brain sediments and synaptosomes following its long-term treatment. The estimated intracellular and intrasynaptosomal Li+ concentrations are lower than predicted by passive distribution according to the Nernst equation, evidencing active extrusion of Li+.Keywords
This publication has 27 references indexed in Scilit:
- Determination of lithium in rat brain regions and synaptosomes by graphite furnace atomic absorption spectrophotometryJournal of Pharmacological Methods, 1990
- Change of synaptic membrane lipid composition and fluidity by chronic administration of lithiumBiochimica et Biophysica Acta (BBA) - Biomembranes, 1988
- A lithium-7 NMR investigation of the lithium ion interaction with phosphatidylcholine-phosphatidylglycerol membranes. Observation of calcium and magnesium ion competitionJournal of Magnetic Resonance (1969), 1985
- Studies on the transport of carnitine in the brain using synaptosomes isolated from guinea-pig cerebral cortexBiochimica et Biophysica Acta (BBA) - Biomembranes, 1983
- The Effect of Long‐term Lithium Treatment on the Incorporation and Distribution of 32P‐Orthosphosphate into the Phospholipids from Rat SynaptosomesActa Pharmacologica et Toxicologica, 1983
- Potassium Movements in Relation to Synaptosomal MorphologyJournal of Neurochemistry, 1980
- Distribution of Sodium, Potassium and Lithium in the Brain of Lithium‐treated RatsActa Pharmacologica et Toxicologica, 1975
- Accumulation of lithium in the particulate fraction of rat brain following its long‐term administrationJournal of Neurochemistry, 1974
- Effect of Lithium on the Uptake of Noradrenaline by SynaptosomesNature, 1967
- REGIONAL STUDIES OF CATECHOLAMINES IN THE RAT BRAIN‐IJournal of Neurochemistry, 1966