Quantitative microlocation of lithium in the brain by a (n, α) nuclear reaction

Thellier, Michel; Wissocq, Jean-Claude; Heurteaux, Catherine

doi:10.1038/283299a0

Cited by 27 publications

(19 citation statements)

References 13 publications

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“…Previously, it was shown that lithium accumulates in areas of the brain with higher cell density and our ToF-SIMS and ICP-AES analysis confirmed this232425. A reason for lithium localizing to regions with higher cellular density could be that lithium uptake occurs chiefly at the cellular body level rather than at the axonal level as previous studies also hypothesized2425. Overall, our findings contribute to a better understanding of lithium accumulation in the developing brain, providing not only a qualitative spatial lithium distribution as judged by ToF-SIMS but also supporting this with the more precise quantitative approach of ICP-AES.…”

Section: Discussionsupporting

confidence: 86%

“…As ToF-SIMS itself as a surface- sensitive technique cannot be considered to be quantitative1935, the present in situ data and complemental ex vivo results highlight its suitability for relative quantification of spatial ion intensity distributions in situ 1521. Previously, it was shown that lithium accumulates in areas of the brain with higher cell density and our ToF-SIMS and ICP-AES analysis confirmed this232425. A reason for lithium localizing to regions with higher cellular density could be that lithium uptake occurs chiefly at the cellular body level rather than at the axonal level as previous studies also hypothesized2425.…”

Section: Discussionsupporting

confidence: 79%

“…This is of particular relevance when studying complex and heterogeneous samples, such as brain tissue, which arguably constitutes the most complex and least understood system in the body202122. Previous studies on adult rodent brain showed that once lithium reaches a steady state, it displays a regional distribution in the brain, and by using a neutron radiation technique the highest lithium concentrations were observed in the thalamus, neo-cortex, the gray matter of the cerebellum and the hippocampus232425.…”

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confidence: 99%

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Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

Zanni

Michno

Martino

et al. 2017

Sci Rep

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Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

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Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

Zanni

Michno

Martino

et al. 2017

Sci Rep

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“…RIA neurons express at least three types of non-NMDA-type ionotropic glutamate receptors, of which GLR-3 and GLR-6 are expressed exclusively in RIA neurons (Brockie et al 2001). Because non-NMDA receptors conduct lithium as well as sodium (Kabakov et al 1998), it is possible that a large number of synapses containing many glutamate receptors promote lithium uptake, resulting in a higher concentration of lithium in RIA neurons than in other neurons, similar to the uneven accumulation of lithium in mouse brain (Thellier et al 1980). Given that C. elegans probably has inositol-producing enzymes other than TTX-7/IMPase as discussed above, dependence of each neuronal subtype on a different enzyme may be an additional reason for the IMPase-dependence of RIA neurons.…”

Section: Loss Of Ttx-7/impase Causes Specific Defects In Ria Interneumentioning

confidence: 99%

Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans

et al. 2006

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Although recent studies have provided significant molecular insights into the establishment of neuronal polarity in vitro, evidence is lacking on the corresponding phenomena in vivo, including correct localization of synaptic components and the importance of this process for function of the nervous system as a whole. RIA interneurons act as a pivotal component of the neural circuit for thermotaxis behavior in the nematode Caenorhabditis elegans and provide a suitable model to investigate these issues, having a neurite clearly divided into pre-and post-synaptic regions. In a screen for thermotaxis mutants, we identified the gene ttx-7, which encodes myo-inositol monophosphatase (IMPase), an inositol-producing enzyme regarded as a bipolar disorder-relevant molecule for its lithium sensitivity. Here we show that mutations in ttx-7 cause defects in thermotaxis behavior and localization of synaptic proteins in RIA neurons in vivo. Both behavioral and localization defects in ttx-7 mutants were rescued by expression of IMPase in adults and by inositol application, and the same defects were mimicked by lithium treatment in wild-type animals. These results suggest that IMPase is required in central interneurons of the mature nervous system for correct localization of synaptic components and thus for normal behavior.[Keywords: C. elegans; thermotaxis behavior; protein localization; synapse; myo-inositol monophosphatase; lithium] Supplemental material is available at http://www.genesdev.org. Received April 19, 2006; revised version accepted October 23, 2006. Neurons are the most highly polarized animal cell type and are composed of several subcellular compartments, including axons, dendrites, and cell bodies, each of which has its own molecular and physiological characteristics. How these polarized compartments are established has been extensively investigated using cultured hippocampal neurons as a model system (Dotti and Banker 1987;Dotti et al. 1988). Recent studies have demonstrated that GSK-3␤ and small GTPase-mediated signaling pathways are critical in assigning axonal fate to the immature neurite in hippocampal neurons (Arimura and Kaibuchi 2005;Jiang et al. 2005). The established axonal compartment is physically separated from the cell body by a molecular diffusional barrier, which is at least partly responsible for maintaining the distinct character of these two compartments (Nakada et al. 2003). However, it remains to be determined whether these mechanisms are common to all neuronal types or other mechanisms exist as well. Furthermore, to understand the physiological importance of polarization and consequent subcellular heterogeneity such as localization of synaptic proteins, it is essential to evaluate how these subcellular phenomena in vivo correlate with the function of neurons and the nervous system as a whole.The nematode Caenorhabditis elegans has a simple nervous system that consists of 302 neurons, the synaptic connectivity of which has been described in its entirety by electron microscopy (White et al...

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“…The difficulty with plant systems is that the cells engaged in the processes of transferring or storing of information are not as easily identified as they are in animal systems. An interesting possibility might consist of studying their interactions with Li"*", especially as we have recently described new methods permitting the study of the location, transport and role of Li"^ in cellu-lar systems despite the lack of any radiotracer of lithium (Thellier et al 1980a, b, Lassalles et al 1980, 1981. The very notion of memory, as applicable to plants, will also have to be rediscussed from an epistemological point of view, especially in relation to other types of memorization mechanism possibly encountered in plants.…”

Section: Discussionmentioning

confidence: 99%

Do memory processes occur also in plants?

Thellier¹,

Desbiez²,

Champagnat³

et al. 1982

Physiologia Plantarum

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Thellier, M., Desbiez, M. O. Champagnat, P. and Kergosien, Y. 1982. Do memory processes occur also in plants? -Physiol. JPlant. 56: 281-284.Plantlets of Bidens pilosus L. "remembered" a symmetry-breaking signal (the puncturing of one of the cotyledons), but expressed it only after being made permissive (by removing the apex). The mean value of the memorization index was 0.52. There was a labile short-temn and a well-fixed long-term memory. The memorization process was dependent on the number of stimuli, .and on the mineral status of the plant.Additional key words -Bidens pilosus, mineral nutrition, lithium. Sciences, B. P. 67, France; M. O. Desbiez and P. Champagnat, Phytomorphogenese, Univ. de Clermont,[4][5][6] M. Thellier (reprint requests), Echange cellulalres, Faculte des

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Quantitative microlocation of lithium in the brain by a (n, α) nuclear reaction

Cited by 27 publications

References 13 publications

Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans

Do memory processes occur also in plants?

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