Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

Fisher, Stephen K.; Novak, James E.; Agranoff, Bernard W.

doi:10.1046/j.1471-4159.2002.01041.x

Cited by 353 publications

(318 citation statements)

References 191 publications

(268 reference statements)

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“…From studies in cultured cells, there is evidence that m-Ins is preferentially located in glial cells (Brand et al, 1993), although it remains uncertain to what extent it is a specific astrocyte marker (Fisher et al, 2002). We may speculate that the dramatic elevation in lesions and NAWM associated with SSPE accompanies the pathology of astrocytic proliferation and gliosis.…”

Section: Discussionmentioning

confidence: 95%

Serial proton spectroscopy in a case of adult-onset subacute sclerosing panencephalitis

Michael

Erfurth

Lüdemann

et al. 2005

Psychiatry Research: Neuroimaging

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A case of subacute sclerosing panencephalitis in a 27-year-old man was serially evaluated with proton magnetic resonance spectroscopy. Metabolic abnormalities included decreased N-acetylaspartate and elevated choline and myo-inositol in a lesion visible on magnetic resonance imaging and in normal-appearing white matter. Lactate appeared increased within the lesion. Metabolic impairment was persistent after intrathecal interferon-a treatment. Spectroscopy pointing to ongoing inflammation, gliosis, and possible membrane turnover was more sensitive than imaging in detecting widespread pathology within the white matter. D

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Section: Discussionmentioning

confidence: 95%

Serial proton spectroscopy in a case of adult-onset subacute sclerosing panencephalitis

Michael

Erfurth

Lüdemann

et al. 2005

Psychiatry Research: Neuroimaging

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“…The fact that the adult IMPA1 À/À mice did not show reduced inositol levels in various brain regions does not rule out inositol depletion as a mechanism of the observed seizures. Several pools of inositol are suggested to exist in the brain (Bersudsky et al, 1994;Brand et al, 1993;Fisher et al, 2002;Frey et al, 1998;Novak et al, 1999Novak et al, , 2000a and the IMPA1-dependent inositol pool likely makes up only a small, possibly spatially delineated but clearly significant part. Actually, inositol depletion as a result of dietary inositol restriction (Shaldubina et al, 2006b) or hyponatremia (Bersudsky et al, 1994) has been shown not to sensitize pilocarpine-induced seizures.…”

Section: Discussionmentioning

confidence: 99%

IMPA1 is Essential for Embryonic Development and Lithium-Like Pilocarpine Sensitivity

Cryns¹,

Shamir

Acker

et al. 2007

Neuropsychopharmacol

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Lithium has been the standard pharmacological treatment for bipolar disorder over the last 50 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. We characterized the phenotype of mice with a dysfunctional IMPA1 gene (IMPA1 À/À ) to study the in vivo physiological functions of IMPA1, in general, and more specifically its potential role as a molecular target in mediating lithium-dependent physiological effects. Homozygote IMPA1 À/À mice died in utero between days 9.5 and 10.5 post coitum (p.c.) demonstrating the importance of IMPA1 in early embryonic development. Intriguingly, the embryonic lethality could be reversed by myo-inositol supplementation via the pregnant mothers. In brains of adult IMPA1 À/À mice, IMPase activity levels were found to be reduced (up to 65% in hippocampus); however, inositol levels were not found to be altered. Behavioral analysis of the IMPA1 À/À mice indicated an increased motor activity in both the open-field test and the forced-swim test as well as a strongly increased sensitivity to pilocarpine-induced seizures, the latter supporting the idea that IMPA1 represents a physiologically relevant target for lithium. In conclusion the IMPA1 À/À mouse represents a novel model to study inositol homeostasis, and indicates that genetic inactivation of IMPA1 can mimic some actions of lithium.

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“…Indeed, an increase in functional anisotropy of subcortical gray matter in HD patients suggests fiber tract disruption may occur throughout the brain (Douaud et al, 2009). Elevated myo-Ins, principally found within astrocytes, is considered a marker for gliosis and is elevated in a number of neurodegenerative diseases (Fisher et al, 2002;Oz et al, 2010a). Similarly, increases in myo-Ins and decreases in NAA have been found in both R6/2 mice and presymptomatic and early stage HD patients (Jenkins et al, 2005;Tsang et al, 2006;Sturrock et al, 2010).…”

Section: Metabolite Changes Reliably Anticipated Volume Changesmentioning

confidence: 99%

Cortical Metabolites as Biomarkers in the R6/2 Model of Huntington's Disease

Zacharoff

Tkáč

Song³

et al. 2011

J Cereb Blood Flow Metab

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To improve the ability to move from preclinical trials in mouse models of Huntington's disease (HD) to clinical trials in humans, biomarkers are needed that can track similar aspects of disease progression across species. Brain metabolites, detectable by magnetic resonance spectroscopy (MRS), have been suggested as potential biomarkers in HD. In this study, the R6/2 transgenic mouse model of HD was used to investigate the relative sensitivity of the metabolite profiling and the brain volumetry to anticipate the disease progression. Magnetic resonance imaging (MRI) and 1 H MRS data were acquired at 9.4 T from the R6/2 mice and wild-type littermates at 4, 8, 12, and 15 weeks. Brain shrinkage was detectable in striatum, cortex, thalamus, and hypothalamus by 12 weeks. Metabolite changes in cortex paralleled and sometimes preceded those in striatum. The entire set of metabolite changes was compressed into principal components (PCs) using Partial Least Squares-Discriminant Analysis (PLS-DA) to increase the sensitivity for monitoring disease progression. In comparing the efficacy of volume and metabolite measurements, the cortical PC1 emerged as the most sensitive single biomarker, distinguishing R6/2 mice from littermates at all time points. Thus, neurochemical changes precede volume shrinkage and become potential biomarkers for HD mouse models.

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Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

Cited by 353 publications

References 191 publications

Serial proton spectroscopy in a case of adult-onset subacute sclerosing panencephalitis

Serial proton spectroscopy in a case of adult-onset subacute sclerosing panencephalitis

IMPA1 is Essential for Embryonic Development and Lithium-Like Pilocarpine Sensitivity

Cortical Metabolites as Biomarkers in the R6/2 Model of Huntington's Disease

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