Role of calcium regulation in pathophysiology model of schizophrenia and possible interventions

Yarlagadda, Atmaram

doi:10.1054/mehy.2001.1511

Cited by 19 publications

(11 citation statements)

References 19 publications

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“…In contrast, NCS-1 expression is increased in the prefrontal cortex of schizophrenic and bipolar patients (17). Unfortunately, little is known about the underlying pathomechanism of these human diseases although misregulation of calcium homeostasis has been proposed to play a role (18,19).…”

Section: Introductionmentioning

confidence: 99%

Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

Schlecker¹,

Boehmerle²,

Jeromin³

et al. 2006

J. Clin. Invest.

133

119

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Regulation and dysregulation of intracellular calcium (Ca 2+ ) signaling via the inositol 1,4,5-trisphosphate receptor (InsP 3 R) has been linked to many cellular processes and pathological conditions. In the present study, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, calcium-binding protein, to purified InsP 3 R type 1 (InsP 3 R1) increased the channel activity in both a calcium-dependent and -independent manner. In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway. To determine whether InsP 3 R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders. Lithium inhibited the enhancing effect of NCS-1 on InsP 3 R1 function, suggesting that InsP 3 R1/NCS-1 interaction is an essential component of the pathomechanism of bipolar disorder.

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Section: Introductionmentioning

confidence: 99%

Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

Schlecker¹,

Boehmerle²,

Jeromin³

et al. 2006

J. Clin. Invest.

133

119

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“…Ca 2ϩ ions are not only crucial in several steps in neuronal signaling during normal brain activity but are also associated with a variety of pathologies such as ischemia, hypoglycemia, and seizures. 16 The involvement of Ca 2ϩ has been implicated in neurometabolic disorders such as in Parkinson disease, 17 Huntington disease, 18 amyotropic lateral sclerosis, 19 schizophrenia, 20,21 muscular dystrophy, 22 etc, suggesting a broad spectral role of Ca in neuropsychiatric disorders. While Ca 2ϩ has been an important target for MR imaging probes, so far, to our knowledge, no agents responsive to neurotransmitters or transmembrane potentials have been reported.…”

Section: Ca Sensingmentioning

confidence: 99%

Smart MR Imaging Agents Relevant to Potential Neurologic Applications

Bonnet¹,

Tóth²

2009

AJNR Am J Neuroradiol

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SUMMARY: Molecular imaging is aimed at the noninvasive visualization of the expression and function of bioactive molecules that often represent specific molecular signatures in disease processes. Any molecular imaging procedure requires an imaging probe that is specific to a given molecular event, which puts an important emphasis on chemistry development. In MR imaging, the past years have witnessed significant advances in the design of molecular agents, though most of these efforts have not yet progressed to in vivo studies. In this review, we present some examples relevant to potential neurobiologic applications. Our aim was to show what chemistry can bring to the area of molecular MR imaging with a focus on the 2 main classes of imaging probes: Gd 3ϩ -based and PARACEST agents. We will discuss responsive probes for the detection of metal ions such as Ca, Zn, Fe, and Cu, pH, enzymatic activity, and oxygenation state.ABBREVIATIONS: BBB ϭ blood-brain barrier; BOLD ϭ blood oxygen levelϪdependent; bpy ϭ bipyridine; C, carbon; Ca ϭ calcium; CEST ϭ chemical exchange saturation transfer; CO 3 ϭ carbonate; Cu ϭ copper; DTPA ϭ diethylene-triamine pentaacetic acid; DOTA ϭ 1,4,7,10-tetraaza-1,4,7,10-tetrakis(carboxymethyl)cyclododecane; Eu ϭ europium; Fe ϭ iron; Gd ϭ gadolinium; H ϭ hydrogen; HSA ϭ human serum albumin; k ex ϭ exchange rate; M ϭ metal ion; Mn ϭ manganese; N ϭ nitrogen; O ϭ oxygen; OH ϭ hydroxide; PARACEST ϭ paramagnetic CEST; PO 4 ϭ phosphate; q ϭ number of water molecules coordinated to Gd 3ϩ ; T 1,2e ϭ electron spin relaxation times; TPEN ϭ N,N,NЈ,NЈ-tetrakis(2-pyridylmethyl)ethylene-diamine; tpps ϭ 5,10,15,20-tetrakis-(p-sulfonatophenyl porphinate; tpy ϭ terpyridine; Yb ϭ ytterbium; Zn ϭ zinc; tau R ϭ reorientational correlation time of the molecule M olecular imaging is an emerging science area aimed at noninvasive visualization of the expression and function of bioactive molecules that often represent specific molecular signatures in disease processes. It seeks the biochemical or physiologic abnormalities underlying the disease, rather than the structural consequences of these abnormalities. Potential clinical applications of molecular imaging have been widely recognized, though the limited sensitivity and specificity of current molecular imaging approaches are often a major roadblock for clinical applications. Besides clinical settings, drug development can also largely benefit from the integration of molecular imaging. Molecular imaging not only allows rationalization of the parameters related to disease processes but it can also replace the common invasive research techniques (such as histology, which requires sacrificing animals for each time point in the experiment) by time-effective repeatable real-time visualization of biologically relevant processes. Currently, progress in the molecular imaging area is simultaneously moving at 3 levels: 1) improving the imaging hardware for use in preclinical and clinical settings, 2) identifying and validating new biologically relevant imaging targets, and 3...

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“…Tnnt 1 is known to have higher Ca 2+ affinity as compared with other subunits in peripheral tissues (Kischel et al, 2005). There is evidence that calcium homeostasis, especially in the context of the central nervous system, may have crucial implications in many neuropsychiatric conditions (Yarlagadda, 2002). Mobilization of calcium, both extra-and intracellularly, has tremendous implications in the brain because of its buffering capacity and its second messenger functions (Yarlagadda, 2002;Eguiagaray et al, 2004).…”

Section: The Significance Of Tnnt 1 Expression In Adult Mouse Brain Imentioning

confidence: 99%

“…There is evidence that calcium homeostasis, especially in the context of the central nervous system, may have crucial implications in many neuropsychiatric conditions (Yarlagadda, 2002). Mobilization of calcium, both extra-and intracellularly, has tremendous implications in the brain because of its buffering capacity and its second messenger functions (Yarlagadda, 2002;Eguiagaray et al, 2004). It will be interesting to explore whether the up-regulated Tnnt 1 expression is a transient stress response after exogenous insults or portends persistent damage or cascade pathways changes that lead to neuropsychiatric diseases observed in the patients treated with these agents.…”

Section: The Significance Of Tnnt 1 Expression In Adult Mouse Brain Imentioning

confidence: 99%

Molecular stress response in the CNS of mice after systemic exposure to interferon-α, ionizing radiation and ketamine

et al. 2009

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We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adult mice 30 minutes after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt

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Role of calcium regulation in pathophysiology model of schizophrenia and possible interventions

Cited by 19 publications

References 19 publications

Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

Smart MR Imaging Agents Relevant to Potential Neurologic Applications

Molecular stress response in the CNS of mice after systemic exposure to interferon-α, ionizing radiation and ketamine

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