Effects of chronic lithium administration on rat brain phosphatidylinositol cycle constituents, membrane phospholipids and amino acids

Pettegrew, Jay W.; Panchalingam, K.; McClure, Richard J.; Gershon, Samuel; Muenz, Larry R.; Levine, Joseph

doi:10.1034/j.1399-5618.2001.30404.x

Cited by 20 publications

(17 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…42 However, a second study with a short treatment course found creatine to be unchanged, but also failed to identify myo-inositol depletion after lithium treatment. 55 This is the first report to show creatine decreasing after long-term treatment with mood-stabilizing medications.…”

Section: Post-mortem Brain Tissue Analysismentioning

confidence: 79%

Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder

et al. 2008

View full text Add to dashboard Cite

Bipolar affective disorder is a severe and debilitating psychiatric condition characterized by the alternating mood states of mania and depression. Both the molecular pathophysiology of the disorder and the mechanism of action of the mainstays of its treatment remain largely unknown. Here, 1 H NMR spectroscopy-based metabonomic analysis was performed to identify molecular changes in post-mortem brain tissue (dorsolateral prefrontal cortex) of patients with a history of bipolar disorder. The observed changes were then compared to metabolic alterations identified in rat brain following chronic oral treatment with either lithium or valproate. This is the first study to use 1 H NMR spectroscopy to study post-mortem bipolar human brain tissue, and it is the first to compare changes in disease brain with changes induced in rat brain following mood stabilizer treatment. Several metabolites were found to be concordantly altered in both the animal and human tissues. Glutamate levels were increased in post-mortem bipolar brain, while the glutamate/glutamine ratio was decreased following valproate treatment, and c-aminobutyric acid levels were increased after lithium treatment, suggesting that the balance of excitatory/inhibitory neurotransmission is central to the disorder. Both creatine and myo-inositol were increased in the post-mortem brain but depleted with the medications. Lastly, the level of N-acetyl aspartate, a clinically important metabolic marker of neuronal viability, was found to be unchanged following chronic mood stabilizer treatment. These findings promise to provide new insight into the pathophysiology of bipolar disorder and may be used to direct research into novel therapeutic strategies.

show abstract

Section: Post-mortem Brain Tissue Analysismentioning

confidence: 79%

Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder

et al. 2008

View full text Add to dashboard Cite

show abstract

“…45 Lithium-7 NMR has been used in an essentially analytical capacity in two related studies. Pettegrew et al 46 investigated the effect of chronic Li on the molecular constituents of rat brain. Brain Li levels in the range of 70 R. A. KOMOROSKI 0.5-0.6 mM were measured directly by 7 Li NMR on excised samples of whole brain tissue vs an inserted capillary standard of Li with shift reagent.…”

Section: Cns Modelsmentioning

confidence: 99%

Biomedical applications of7Li NMR

Komoroski

2005

NMR Biomed.

View full text Add to dashboard Cite

The biomedical applications of 7 Li MRS and MRI have been progressing slowly. The interest derives primarily from the clinical use of Li to treat bipolar disorder. One area of concern is the nature of ionic transport and binding, so as to elucidate the mechanism(s) of therapeutic action and toxicity. Another is the development of a non-invasive, in vivo analytical tool to measure brain Li concentration and environment in humans, both as an adjunct to treatment and as a mechanistic probe. Here we review the most recent progress toward these goals.

show abstract

“…Their average serum lithium level was 0.65 ± 0.08 mmol/L at the end of the 30-day period. This experimental period was selected for study because although the efficacy of lithium on individuals as a mood stabilizer is associated with prolonged treatment, in studies concerning lithium effects in rat tissues the usual duration of treatment is between 15 to 30 days [21,35]. Animals were treated with lithium intraperitoneally instead of per os because the latter treatment evokes more pronounced renal problems to experimental species with compared to those after other routes of administration [36].…”

Section: Lithium Administrationmentioning

confidence: 99%

Effect of lithium administration on collagen and breaking pressure of the rat thoracic descending aorta

Tzaphlidou¹,

Berillis²

2004

J Trace Elements Exper Med

View full text Add to dashboard Cite

Lithium is widely used in medicine as an antidepressive drug. Despite abundant literature on the subject, questions on the effects of lithium on collagen, which is one of the major components of tissues and organs, are far from being answered. We have examined the effects of lithium chloride (1.5 mEq Li/kg of body weight) on rat thoracic descending aorta: 1) on collagen fibrils by electron microscopy and image analysis and 2) on breaking pressure. Animals were sacrificed 1 day, 2, and 12 months after the end of a 30 consecutive days experimental period. In all cases investigated, structural abnormalities in collagen fibrils, at the ultrastructural level, were found. These abnormalities consist of decreased mean diameter and high variability in width as well as marked disorganization in the packing of the fibrils. The observed alterations seem to be permanent. Rupture of the rat thoracic aorta following pressure is significantly influenced by lithium.

show abstract

Effects of chronic lithium administration on rat brain phosphatidylinositol cycle constituents, membrane phospholipids and amino acids

Abstract: Lithium alters levels of key membrane phospholipids and appears to affect the balance between inhibitory and excitatory amino acids in rat brain. Co-administration of myo-inositol attenuates some of these lithium effects on brain metabolites.

Cited by 20 publications

References 91 publications

Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder

Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder

Biomedical applications of7Li NMR

Effect of lithium administration on collagen and breaking pressure of the rat thoracic descending aorta

Contact Info

Product

Resources

About