The cholinergic receptor-linked phosphoinositide metabolism in mouse cerebrum and cerebellum in vivo

Lin, Tai-An; Zhang, Jianping; Sun, Grace Y.

doi:10.1016/0006-8993(93)90816-6

Cited by 4 publications

(2 citation statements)

References 24 publications

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“…The inositol-depletion hypothesis suggests that because of this inhibition of the PI-cycle by lithium, there is decreased calcium release intracellularly [121,122]. This hypothesis has been supported in several pre-clinical studies [117,[123][124][125][126][127][128][129][130][131][132][133][134]. It is also of interest to note that some clinical studies suggest that there may also be an intrinsic abnormality in the PI-cycle in bipolar patients.…”

Section: Study Field Strength N Findings Notesmentioning

confidence: 96%

Current Pathophysiological Findings in Bipolar Disorder and in its Subtypes

Silverstone¹,

McGrath²,

Wessels³

et al. 2005

CPSR

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There have been many studies that have examined various aspects of the pathophysiology of bipolar disorder, with many positive findings in several areas of neuroimaging and metabolic abnormality. These studies might allow some conclusions to be drawn about the underlying pathophysiology. Additionally, it is of significant interest to determine if there are pathophysiological differences between patients with bipolar disorder type I (BPD-I) and those with bipolar disorder type II (BPD-II). The present review examines imaging studies in bipolar patients of possible structural changes (magnetic resonance imaging (MRI)) functional changes (focusing on functional MRI (fMRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT)), and those examining brain chemistry (utilizing magnetic resonance spectroscopy (MRS)). Metabolic studies reviewed were those that examined 3-methoxy-4-hydroxyphenylglycol (MHPG), cellular calcium, and protein kinase C (PKC). The results clearly suggest that BPD patients differ from controls on many of these measures. However, while there is evidence from genetic studies suggesting possible differences between BPD-II patients and BPD-I patients, the neuroimaging and metabolic studies to date do not support this, and there appear to be no consistent pathophysiological differences between these subtypes from evidence available at present.

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Section: Study Field Strength N Findings Notesmentioning

confidence: 96%

Current Pathophysiological Findings in Bipolar Disorder and in its Subtypes

Silverstone¹,

McGrath²,

Wessels³

et al. 2005

CPSR

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“…After equilibration of labeled inositol in the brain, regional differences in inositol metabolism were observed. 16 Using this protocol, we demonstrated the inhibitory effect of acute ethanol on lithium-mediated accumulation of IP,, suggesting a decrease in the poly-PI signaling activity. However, the effect of chronic ethanol administration on the poly-PI signaling pathway has not been examined.…”

mentioning

confidence: 96%

Chronic Ethanol Inhibits Inositol Metabolism in Specific Brain Regions

Zhang¹,

Xia²,

Sun³

1997

Alcoholism Clin & Exp Res

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Many neurotransmitters and hormones in the nervous system transmit signals through receptors coupled to the poly-phosphoinositide (PI) signaling pathway. In this study, an in vivo protocol with [3H]inositol was used to examine the effect of chronic ethanol administration on inositol metabolism and poly-PI turnover in the cerebral cortex, hippocampus, and cerebellum of mouse brain. C57BL/6 mice were given a nutritionally complete liquid diet containing either ethanol (5%, w/v) or isocaloric sucrose for 2 months. Mice were injected intracerebrally with [3H]inositol; after 16 or 24 hr, they were injected intraperitoneally with lithium (8 mEq/kg body weight) to inhibit the inositol monophosphatase (IP1) activity. All mice were decapitated 4 hr after lithium injection. Labeled inositol phospholipids accounted for 16 to 23% of total labeled inositol in different regions of control mouse brain, and the percentages in the hippocampus were consistently higher than the cerebral cortex and cerebellum. In control mice, the percentages of labeled IP1 after a 4-hr lithium treatment were 11.5%, 9.9%, and 3.7% for cerebral cortex, hippocampus, and cerebellum, respectively. Chronic ethanol feeding resulted in a significant (p < 0.05) decrease in the percent of labeled IP1 and inositol phospholipids, and this effect was observed in the cerebral cortex and, to a lesser extent, hippocampus but not cerebellum. When ratios of labeled IP1 were expressed against labeled inositol phospholipids as an index of the poly-PI turnover activity, significant decreases in IP/lipid ratios were observed in the cerebral cortex, but not the hippocampus or cerebellum. Although mice killed 24 + 4 hr after the last ethanol feeding would have experienced an 8-hr period of ethanol withdrawal, compared with the 16 + 4-hr group, no differences in IP/lipid ratios were observed between the two time groups. These results illustrate regional differences in the effect of chronic ethanol on inositol metabolism in the brain, but no difference in poly-PI turnover in brain due to ethanol withdrawal.

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In utero hypoxic ischemia decreases the cholinergic agonist-stimulated poly-phosphoinositide turnover in the developing rat brain

Hersey

Zhang

et al. 1995

Neurochem Res

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Perinatal hypoxic-ischemic (HI) insult is known to cause cellular and molecular disturbances leading to functional and behavioral abnormalities during brain development. In this study, we examined the effects of an in utero HI insult on poly-phosphoinositide turnover in vivo in the cerebrum and cerebellum as well as cholinergic-stimulated turnover in cortical slices from developing rat brain. In utero HI treatment was carried out by clamping the uterine blood vessels of near-term fetuses for 5, 10 and 15 min followed by resuscitation of the newborn pups. The in vivo protocol for examining poly-PI signaling activity in 2 week-old pup brain involved intracerebral injection of [3H]inositol for 16 hr and subsequent intraperitoneal injection with lithium (8 meq/kg) for 4 hr prior to decapitation. In the control pups, lithium elicited a 2.6 fold increase in labeled inositol phosphate (IP) in the cerebrum as compared to a 1.3 fold increase in the cerebellum. In utero HI insult (5 to 15 min) resulted in a small increase in labeled IP in the cerebrum but not in the cerebellum. Carbachol stimulation of poly-PI turnover was examined in brain slices prelabeled with [3H]inositol in vivo. Incubation of the prelabeled slices with carbachol in the presence of LiCl (10 mM) resulted in a time-, dose- and age-dependent increase in labeled IP. Brain slices from 2 week-old pups that experienced in utero HI-treatment for 10 and 15 min (but not 5 min) showed a significant decrease in carbachol-stimulation of labeled IP as compared with control pups. These results indicate the effects of in utero HI on the choninergic-stimulated poly-PI signaling pathway and its implication on related functional deficits in the developing brain.

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The cholinergic receptor-linked phosphoinositide metabolism in mouse cerebrum and cerebellum in vivo

Cited by 4 publications

References 24 publications

Current Pathophysiological Findings in Bipolar Disorder and in its Subtypes

Current Pathophysiological Findings in Bipolar Disorder and in its Subtypes

Chronic Ethanol Inhibits Inositol Metabolism in Specific Brain Regions

In utero hypoxic ischemia decreases the cholinergic agonist-stimulated poly-phosphoinositide turnover in the developing rat brain

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