Differences in the metabolism of inositol and phosphoinositides by cultured cells of neuronal and glial origin

Glanville, N. Theresa; Byers, David M.; Cook, Harold W.; Spence, Matthew W.; Palmer, Frederick B.

doi:10.1016/0005-2760(89)90265-8

Cited by 111 publications

(77 citation statements)

References 46 publications

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“…Astrocytes appear to be particularly important for the myo-inositol homeostasis in the brain since they accumulate inositol more intensely (Glanville et al 1989) and express much higher amounts of SMIT mRNA than neurons (our unpublished results). Thus, while the original inositol depletion hypothesis has only implied neurons as the target of lithiums dampening effect on phosphoinositol signaling, there is no inherent reason to restrict this action to neuronal cells, since also glial cells express this signal transduction system (Verkhratsky et al 1998) and are actively involved in information processing.…”

Section: Discussionmentioning

confidence: 60%

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

Lubrich

Calker

1999

Neuropsychopharmacology

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Manic-depressive disorder is an at least in part genetically transmitted illness that affects one to two percent of the population and is characterized by episodic mood swings in the form of depressive, and manic episodes (Goodwin and Jamison 1990). It can be effectively treated acutely and prophylactically by antibipolar drugs like lithium salts, carbamazepine and valproate. Recent evidence indicates that lithium's beneficial effects might be related to a modulation of cellular signal transducing mechanisms (for review see Berridge et al. 1989;Jope and Williams 1994). In particular, the "inositol depletion" hypothesis (Berridge et al. 1989) conjectures that lithium might act via depletion of susceptible brain areas of myo-inositol, which is necessary to form inositolphospholipids, an integral part of the cell membrane. The breakdown of these lipids by receptor-triggered activation of phospholipase C leads to the formation of the two second messenger molecules, inositol-1,4,5-trisphosphate and diacylglycerol (DAG), which regulate many cellular activities. The lithium induced decrease of the cellular inositol content is postulated to selectively impair pathological overactivation of this system via insufficient supply of inositol for the resynthesis of inositolphospholipid or perhaps other mechanisms secondary to inositol depletion such as activation of protein kinase C (PKC) by accumulated DAG (Jope and Williams 1994). The reason for lithium's inositol depleting effect and for its selectivity for overactivated neural circuits is believed to be the inhibition of inositolmonophosphatase (IMPase), which is of the uncompetitive type and therefore the more pronounced the more substrate (inositolmonophosphate, IMP) is formed by breakdown of inositolphospholipids. The inositol depletion hypothesis rests

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Section: Discussionmentioning

confidence: 60%

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

Lubrich

Calker

1999

Neuropsychopharmacology

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“…MI is primarily isolated from glial cells (34). MI levels correlate with glial proliferation in inflammatory CNS demyelination (23).…”

Section: Discussionmentioning

confidence: 99%

¹ H MR spectroscopy in common dementias

Kantarci

Petersen²,

Boeve³

et al. 2004

Neurology

214

147

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Objective-To determine the 1 H MR spectroscopic (MRS) findings and inter-group differences among common dementias: Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD).Methods-We consecutively recruited 206 normal elderly, 121 patients with AD, 41 with FTLD, 20 with DLB, and 8 with VaD. We evaluated the 1 H MRS metabolite ratio changes in common dementias with respect to normal, and also differences among the common dementias.Results-N-acetylaspartate/Creatine (NAA/Cr) was lower than normal in patients with AD, FTLD, and VaD. Myo-inositol (mI)/Cr was higher than normal in patients with AD and FTLD. Choline (Cho)/Cr was higher than normal in patients with, AD, FTLD, and DLB. There were no metabolite differences between patients with AD and FTLD, nor between patients with DLB and VaD. NAA / Cr was lower in patients with AD and FTLD than DLB. MI /Cr was higher in patients with AD and FTLD than VaD. MI /Cr was also higher in patients with FTLD than DLB.Conclusions-NAA/Cr levels are decreased in dementias that are characterized by neuron loss such as AD, FTLD, and VaD. MI/Cr levels are elevated in dementias that are pathologically characterized by gliosis such as AD and FTLD. Cho/Cr levels are elevated in dementias that are characterized by a profound cholinergic deficit such as AD and DLB.

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“…Accordingly, Yao et al (1999) reported an increase of phosphatidylinositol that may be incorporated into lipid membranes (Quarles et al, 2006) during mouse brain development. In several neurological disorders, myoinositol was found to be increased (Bitsch et al, 1999;Horská et al, 2009;Kantarci, 2007) and this is generally assumed to be a marker of gliosis, based on the fact that higher myo-inositol levels are found in cultured astrocytes as compared to neurons in vitro (Brand et al, 1993;Glanville et al, 1989). However, brain myo-inositol levels may not always correlate with other molecular markers of gliosis (Duarte et al, 2009a;Kim et al, 2005;Kunz et al, 2011).…”

Section: Neurotransmitter Metabolismmentioning

confidence: 99%

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

et al. 2012

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Differences in the metabolism of inositol and phosphoinositides by cultured cells of neuronal and glial origin

Cited by 111 publications

References 46 publications

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

¹ H MR spectroscopy in common dementias

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

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Differences in the metabolism of inositol and phosphoinositides by cultured cells of neuronal and glial origin

Cited by 111 publications

References 46 publications

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

1 H MR spectroscopy in common dementias

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

Contact Info

Product

Resources

About

¹ H MR spectroscopy in common dementias