Lithium-induced increase in human brain grey matter

Moore, Gregory J.; Bebchuk, Joseph M.; Wilds, Ian B.; Chen, Guang; Menji, Husseini K

doi:10.1016/s0140-6736(00)02793-8

Cited by 597 publications

(331 citation statements)

References 5 publications

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“…Lithium's ability to block NMDA-initiated increments in k* for AA (this paper) is consistent with evidence that chronic lithium can be neuroprotective in animal models of neurodegeneration and even in BD patients (Moore et al, 2000;Rowe and Chuang, 2004;Zarate et al, 2003). Excess PLA 2 -mediated release of AA, with concurrent formation of excess lyso-phospholipids, can engender neurotoxic sequellae (Bazan et al, 1995;Farooqui et al, 1997;Sapirstein and Bonventre, 2000).…”

Section: Discussionsupporting

confidence: 88%

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

106

132

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It has been proposed that lithium is effective in bipolar disorder (BD) by inhibiting glutamatergic neurotransmission, particularly via N-methyl-D-aspartate receptors (NMDARs). To test this hypothesis and to see if the neurotransmission could involve the NMDARmediated activation of phospholipase A 2 (PLA 2 ), to release arachidonic acid (AA) from membrane phospholipid, we administered subconvulsant doses of NMDA to unanesthetized rats fed a chronic control or LiCl diet. We used quantitative autoradiography following the intravenous injection of radiolabeled AA to measure regional brain incorporation coefficients k* for AA, which reflect receptormediated activation of PLA 2 . In control diet rats, NMDA (25 and 50 mg/kg i.p.) compared with i.p. saline increased k* significantly in 49 and 67 regions, respectively, of the 83 brain regions examined. The regions affected were those with reported NMDARs, including the neocortex, hippocampus, caudate-putamen, thalamus, substantia nigra, and nucleus accumbens. The increases could be blocked by pretreatment with the specific noncompetitive NMDA antagonist MK-801 ((5R,10S)-( + )-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine hydrogen maleate) (0.3 mg/kg i.p.), as well by a 6-week LiCl diet sufficient to produce plasma and brain lithium concentrations known to be effective in BD. MK-801 alone reduced baseline values for k* in many brain regions. The results show that it is possible to image NMDA signaling via PLA 2 activation and AA release in vivo, and that chronic lithium blocks this signaling, consistent with its suggested mechanism of action in BD.

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Section: Discussionsupporting

confidence: 88%

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

106

132

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“…Manji and co-workers Chen et al, 1999b) have demonstrated in vivo that the apoptosis-inhibiting gene bcl-2 is induced both by lithium and valproate, assigning a potential neuroprotective role to these mood stabilizers. This group also reported that lithium treatment is associated with an increase in grey matter volume in patients (Moore et al, 2000). Importantly, valproate also inhibits GSK-3b .…”

Section: Introductionmentioning

confidence: 86%

Lithium- and Valproate-Induced Alterations in Circadian Locomotor Behavior in Drosophila

Dokucu

Taghert

2005

Neuropsychopharmacol

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Lithium and valproate are commonly used mood stabilizers, but their action pathways are not clearly understood. They also suffer from multiple toxic effects that limit their utility. Elucidating their action mechanisms could lead to newer agents and better understanding of the etiopathogenesis of bipolar disorder. We have expanded the study of signaling mechanisms of lithium and valproate by using Drosophila circadian locomotor activity as a robust behavioral assay that is amenable to genetic manipulations. We demonstrate that lithium affects the circadian system of Drosophila similarly to what has been reported in the mammalian studies. We show that lithium and valproate share effects on the circadian locomotor activity of Drosophila: they lengthen the period of circadian rhythms and increase arrhythmicity. Valproate exerts these effects in a weaker fashion than does lithium. We also tested the circadian alterations in multiple mutant lines of Drosophila bearing defects in the GSK-3b gene and other clock genes in response to lithium administration. We show that lithium partially rescues the shortening of circadian period when the GSK-3b gene is overexpressed only in specific circadian pacemaker neurons, thus implicating GSK-3b as a component in lithium's effect on the circadian oscillator. Moreover, lithium also lengthens the period in GSK-3b heterozygous mutants and doubletime long mutants. These results establish a basis for using Drosophila genetics to investigate more fully lithium and valproate action mechanisms.

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“…Proton magnetic resonance spectroscopy has been used to show that total gray-matter content in the human brain of Nacetylaspartate (NAA, a putative marker of neuronal variability and function 172,173 ) were significantly increased after 4 weeks of lithium treatment. 174 In a longitudinal highresolution volumetric MRI study in well-characterized, medication-free bipolar depressed subjects (Moore et al, submitted), total brain gray matter (GM), prefrontal GM, and left subgenual GM were determined at baseline and after 4 weeks of blinded lithium treatment. 175 Significant increases in total brain GM in bipolar subjects were observed after chronic lithium administration.…”

Section: Neurotrophic Effects Of Lithium and Divalproexmentioning

confidence: 99%

Neural circuitry and neuroplasticity in mood disorders: Insights for novel therapeutic targets

Carlson¹,

Singh²,

Zarate³

et al. 2006

NeuroRX

136

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Summary:Major depressive disorder and bipolar disorder are severe mood disorders that affect the lives and functioning of millions each year. The majority of previous neurobiological research and standard pharmacotherapy regimens have approached these illnesses as purely neurochemical disorders, with particular focus on the monoaminergic neurotransmitter systems. Not altogether surprisingly, these treatments are inadequate for many individuals afflicted with these devastating illnesses. Recent advances in functional brain imaging have identified critical neural circuits involving the amygdala and other limbic structures, prefrontal cortical regions, thalamus, and basal ganglia that modulate emotional behavior and are disturbed in primary and secondary mood disorders. Growing evidence suggests that mechanisms of neural plasticity and cellular resilience, including impairments of neurotrophic signaling cascades as well as altered glutamatergic and glucocorticoid signaling, underlie the dysregulation in these circuits. The increasing ability to monitor and modulate activity in these circuits is beginning to yield greater insight into the neurobiological basis of mood disorders. Modulation of dysregulated activity in these affective circuits via pharmacological agents that enhance neuronal resilience and plasticity, and possibly via emerging nonpharmacologic, circuitry-based modalities (for example, deep brain stimulation, magnetic stimulation, or vagus nerve stimulation) offers promising targets for novel experimental therapeutics in the treatment of mood disorders.

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Lithium-induced increase in human brain grey matter

Cited by 597 publications

References 5 publications

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Lithium- and Valproate-Induced Alterations in Circadian Locomotor Behavior in Drosophila

Neural circuitry and neuroplasticity in mood disorders: Insights for novel therapeutic targets

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