Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging

Ramaprasad, S.; Ripp, Elzbieta; Pi, Jiaxiong; Lyon, Melvin

doi:10.1016/j.mri.2005.07.007

Cited by 19 publications

(23 citation statements)

References 16 publications

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“…We evaluated the expression of Homer genes by means of in situ hybridization histochemistry, focusing on the cortex, caudate-putamen, and nucleus accumbens; all of these areas are believed to be involved in the pathophysiology of bipolar disorder (Green et al, 2007) and in the mechanism of action of mood stabilizers (Ramaprasad et al, 2005). We chose to explore both inducible and constitutive Homer isoforms (i.e.…”

Section: Introductionmentioning

confidence: 99%

Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and Inositol 1,4,5-trisphosphate receptor

Bartolomeis¹,

Tomasetti²,

Cicale³

et al. 2012

European Neuropsychopharmacology

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Homer proteins are associated with both dopaminergic and glutamatergic function. In addition, these proteins are implicated in many signal transduction pathways that are also putative targets of the mood stabilizers lithium and valproate (VPA). This study investigated the effect of in vivo chronic administration of therapeutically-relevant doses of lithium and VPA on the expression of the inducible (Homer1a and ania-3) and constitutive (Homer1b/c) isoforms of the Homer1 gene in rat brain, and of two other Homer-related genes: Inositol 1,4,5 trisphosphate receptor (IP3R) and Shank. Homer1b/c was significantly decreased in cortex by VPA, and in striatal and accumbal subregions by both lithium and VPA. Both mood stabilizers reduced Homer1b/c expressionin the dorsolateral caudate-putamen, while only VPA decreased gene expression in all other striatal subregions. Shank and IP3R were downregulated by both mood stabilizers in the cortex. Neither chronic lithium nor VPA affected Homer immediate-early genes. These results suggest that lithium and VPA similarly modulate the expression of structural postsynaptic genes with topographic specificity in cortical and subcortical regions. Thus, Homer may represent an additional molecular substrate for mood stabilizers, and a potential link with dopaminergic function.

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Section: Introductionmentioning

confidence: 99%

Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and Inositol 1,4,5-trisphosphate receptor

Bartolomeis¹,

Tomasetti²,

Cicale³

et al. 2012

European Neuropsychopharmacology

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“…The images, however, suggest a predominantly cerebral localization of 6 Li, in particular considering that the maximum signal does not colocalize with major blood vessels. Although lithium uptake into the brain is considered slow, it is of interest to note that all studies measuring lithium uptake show a sizeable fraction of their maximum lithium signal in the first measurement within minutes (5, 19, 20). Our present study suggests that a sufficient fraction of lithium enters the brain over the time of 6 Li hyperpolarization, i.e., 3–5 min.…”

Section: Discussionmentioning

confidence: 99%

“…It naturally exists as a mixture of two stable isotopes (3): lithium‐6 (7.42%) and lithium‐7 (92.58%). Because of its higher natural abundance, shorter relaxation times, and higher relative sensitivity, 7 Li NMR has been established as a noninvasive tool to study lithium pharmacokinetics and distribution in vivo (4, 5). Given the interest in psychiatric treatment, most studies have focused on the brain.…”

mentioning

confidence: 99%

Hyperpolarized lithium‐6 as a sensor of nanomolar contrast agents

Heeswijk

Uffmann

Comment

et al. 2009

Magnetic Resonance in Med

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Lithium is widely used in psychotherapy. The 6Li isotope has a long intrinsic longitudinal relaxation time T1 on the order of minutes, making it an ideal candidate for hyperpolarization experiments. In the present study, we demonstrated that lithium-6 can be readily hyperpolarized within 30 min, while retaining a long polarization decay time on the order of a minute. We used the intrinsically long relaxation time for the detection of 500 nM contrast agent in vitro. Hyperpolarized lithium-6 was administered to the rat and its signal retained a decay time on the order of 70 s in vivo. Localization experiments imply that the lithium signal originated from within the brain and that it was detectable up to 5 min after administration. We conclude that the detection of sub-micromolar contrast agents using hyperpolarized NMR nuclei such as 6Li may provide a novel avenue for molecular imaging.

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“…Some activity was also seen in prefrontal cortex, but only minimal amounts in the cerebellum and metencephalic brainstem [71]. A 7 Li and 1 H magnetic resonance spectroscopy analysis of the relationship between brain lithium levels and the metabolites N-acetyl aspartate and myo-inositol in the anterior cingulate cortex of older adults with bipolar disorder showed a direct association between brain lithium and higher levels of both metabolites.…”

Section: Journal Of Diagnostic Imaging Inmentioning

confidence: 91%

“…A 7 Li magnetic resonance spectroscopy study of the distribution and regional pharmacokinetics of lithium in rat brain suggested that lithium is most active in a region stretching from the anterior cingulate cortex and striatum to the caudal midbrain, with greatest activity in the preoptic area and hypothalamic region. Some activity was also seen in prefrontal cortex, but only minimal amounts in the cerebellum and metencephalic brainstem [71]. A 7 Li and 1 H magnetic resonance spectroscopy analysis of the relationship between brain lithium levels and the metabolites N-acetyl aspartate and myo-inositol in the anterior cingulate cortex of older adults with bipolar disorder showed a direct association between brain lithium and higher levels of both metabolites.…”

Section: Lithiummentioning

confidence: 91%

NMR-Active Nuclei for Biological and Biomedical Applications

Patching¹

2016

J Diagn Imaging Ther

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Nuclear magnetic resonance (NMR) spectroscopy is a principal well-established technique for analysis of chemical, biological, food and environmental samples. This article provides an overview of the properties and applications of NMR-active nuclei (39 nuclei of 33 different elements) used in NMR measurements (solution-and solid-state NMR, magnetic resonance spectroscopy, magnetic resonance imaging) with biological and biomedical systems and samples. The samples include biofluids, cells, tissues, organs or whole body from different organisms (humans, animals, bacteria, fungi, plants) for detecting and quantifying metabolites or environmental samples (water, soils, sediments). Isolated biomolecules (peptides, proteins, nucleic acids) can be analysed for elucidation of atomic-resolution structure, conformation and dynamics and for characterisation of ligand and drug binding, and of protein-ligand, protein-protein and protein-nucleic acid interactions. NMR can be used for drug screening and pharmacokinetics and to provide information in the design and discovery of new drugs. NMR can also measure translocation of ions and small molecules across lipid bilayers and membranes, characterise structure, phase behaviour and dynamics of membranes and elucidate atomic-resolution structure, orientation and dynamics of membrane-embedded peptides and proteins.Keywords: biological and biomedical applications; drug screening; dynamics; magnetic resonance imaging; membrane proteins; metabolomics; MRI; NMR-active nuclei; nuclear magnetic resonance; protein structure INTRODUCTION1 UCLEAR magnetic resonance (NMR) spectroscopy is one of the principal techniques used for analysis of biological and biomedical systems and samples. This can include the identification, quantification and monitoring of ions, small molecules and biomolecules in studies of metabolism and biological function in human and animal cells and tissues, bacterial cells and spores, fungi and plants. Similar types of measurements can be performed on environmental samples such as water, soils and sediment. NMR is able to elucidate atomic-resolution structure, conformation, molecular mechanism, dynamics and exchange processes (on timescales of picoseconds to seconds) in biomolecules, especially peptides, proteins and nucleic acids. NMR can be used for the observation, quantification and characterisation of ligand and drug binding to biomolecules, and for characterisation of ligandprotein, protein-protein and protein-nucleic acid interactions. NMR can be used for drug screening and it can acquire structural, binding and kinetic information for the design and discovery of new drugs. It can then monitor the absorption, distribution, metabolism and excretion (ADME) of administered drugs in pharmacokinetics studies. OPEN ACCESS PEER-REVIEWED*NMR can be used for the observation, quantification and kinetic characterisation of ion and smallmolecule translocation across lipid bilayers and biological membranes, including those of cells, tissues and vesicles. Solid-state NM...

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Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging

Cited by 19 publications

References 16 publications

Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and Inositol 1,4,5-trisphosphate receptor

Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and Inositol 1,4,5-trisphosphate receptor

Hyperpolarized lithium‐6 as a sensor of nanomolar contrast agents

NMR-Active Nuclei for Biological and Biomedical Applications

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