PK11195 might selectively suppress the quinolinic acid-induced enhancement of anaerobic glycolysis in glial cells

Momosaki, Sotaro; Imamoto, Natsumi; Hosoi, Rie; Sawada, Yuko; Abe, Kohji; Zhang, Ming Rong; Ito, Osamu

doi:10.1016/j.brainres.2010.04.063

Cited by 3 publications

(2 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that TSPO may not be the optimal target for imaging microglial activation and neuroinflammation in schizophrenia. This might partly be due to other TSPO mechanisms related to astrocytes, TSPO density, 50 glucose metabolism, 51 glial mitochondria 52 or transcriptional events 53 that contribute to the PET TSPO signal, potentially underlying the mixed results and heterogeneity observed across and within studies. 18 , 20 In addition, microglial activation is a highly diverse and dynamic process, involving classically pro-inflammatory (M1) and neuroprotective (M2) phenotypes, which may change in disease-specific contexts.…”

Section: Discussionmentioning

confidence: 99%

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

et al. 2017

View full text Add to dashboard Cite

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.

show abstract

Section: Discussionmentioning

confidence: 99%

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

et al. 2017

View full text Add to dashboard Cite

show abstract

“…[ 13 N]Ammonia uptake after infusion of MSO Microinjection of MSO (50 nmol) into the striatum was carried out with minor modifications as previously reported (Momosaki et al, 2007(Momosaki et al, , 2010. Briefly, rats were anesthetized with 2% of isoflurane, and MSO (50 nmol) was infused into one side of the striatum, according to the Atlas of Paxinos and Watson, as follows: 0.2 mm anterior to the bregma, 3.2 mm lateral to the midline, and 6.5 mm below the cortical surface.…”

Section: Materials and Methods Animals And Chemicalsmentioning

confidence: 99%

Assessment of glutamine synthetase activity by [¹³N]ammonia uptake in living rat brain

Momosaki

Ito

Tonomura

et al. 2014

Synapse

Self Cite

View full text Add to dashboard Cite

Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [(13) N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [(13) N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [(13) N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ-glutamyl transferase reaction. Autoradiograms showed a decrease of [(13) N]ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [(15) O]H2 O. The reduction of [(13) N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [(13) N]ammonia may enable measurement of GS activity in the living brain.

show abstract

Treatment of Donor Cell/Embryo with Different Approaches to Improve Development After Nuclear Transfer

Mizutani

Wakayama

2014

Methods in Molecular Biology

View full text Add to dashboard Cite

The successful production of cloned animals by somatic cell nuclear transfer (SCNT) is a promising technology with many potential applications in basic research, medicine, and agriculture. However, the low efficiency and the difficulty of cloning are major obstacles to the widespread use of this technology. Since the first mammal cloned from an adult donor cell was born, many attempts have been made to improve animal cloning techniques, and some approaches have successfully improved its efficiency. Nuclear transfer itself is still difficult because it requires an accomplished operator with a practiced technique. Thus, it is very important to find simple and reproducible methods for improving the success rate of SCNT. In this chapter, we will review our recent protocols, which seem to be the simplest and most reliable method to date to improve development of SCNT embryos.

show abstract

PK11195 might selectively suppress the quinolinic acid-induced enhancement of anaerobic glycolysis in glial cells

Cited by 3 publications

References 25 publications

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

Assessment of glutamine synthetase activity by [¹³N]ammonia uptake in living rat brain

Treatment of Donor Cell/Embryo with Different Approaches to Improve Development After Nuclear Transfer

Contact Info

Product

Resources

About

PK11195 might selectively suppress the quinolinic acid-induced enhancement of anaerobic glycolysis in glial cells

Cited by 3 publications

References 25 publications

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain

Treatment of Donor Cell/Embryo with Different Approaches to Improve Development After Nuclear Transfer

Contact Info

Product

Resources

About

Assessment of glutamine synthetase activity by [¹³N]ammonia uptake in living rat brain