Knockdown of phospholipase C-β1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes

Background

Decreased expression of phospholipase C-β1 (PLC-β1) has been observed in the brains of patients with schizophrenia, but, to our knowledge, no studies have shown a possible association between this altered PLC-β1 expression and the pathogenesis of schizophrenia. Although PLC-β1-null (PLC-β1^−/−) mice exhibit multiple endophenotypes of schizophrenia, it remains unclear how regional decreases in PLC-β1 expression in the brain contribute to specific behavioural defects.

Methods

We selectively knocked down PLC-β1 in the medial prefrontal cortex (mPFC) using a small hairpin RNA strategy in mice.

Results

Silencing PLC-β1 in the mPFC resulted in working memory deficits, as assayed using the delayed non-match-to-sample T-maze task. Notably, however, other schizophrenia- related behaviours observed in PLC-β1^−/− mice, including phenotypes related to locomotor activity, sociability and sensorimotor gating, were normal in PLC-β1 knockdown mice.

Limitations

Phenotypes of PLC-β1 knockdown mice, such as locomotion, anxiety and sensorimotor gating, have already been published in our previous studies. Further, the neural mechanisms underlying the working memory deficit in mice may be different from those in human schizophrenia.

Conclusion

These results indicate that PLC-β1 signalling in the mPFC is required for working memory. Importantly, these results support the notion that the decrease in PLC-β1 expression in the brains of patients with schizophrenia is a pathogenically relevant molecular marker of the disorder.     

Olfactory performance and resting state functional connectivity in non‐demented drug naïve patients with Parkinson's disease

Olfactory performance in Parkinson's disease (PD) is closely associated with subsequent cognitive decline. In the present study, we analyzed the olfaction‐dependent functional connectivity with a hypothesis that olfactory performance would influence functional connectivity within key brain areas of PD. A total of 110 nondemented drug‐naïve patients with PD were subdivided into three groups of high score (PD‐H, n = 23), middle score (PD‐M, n = 64), and low score (PD‐L, n = 23) based on olfactory performance. We performed the resting‐state functional connectivity with seed region of interest in the posterior cingulate cortex (PCC) and caudate. An analysis of functional connectivity revealed that PD‐L patients exhibited a significant attenuation of cortical functional connectivity with the PCC in the bilateral primary sensory areas, right frontal areas, and right parietal areas compared to PD‐H or PD‐M patients. Meanwhile, PD‐L patients exhibited a significant enhancement of striatocortical functional connectivity in the bilateral occipital areas and right frontal areas compared to PD‐H or PD‐M patients. In the voxel‐wise correlation analysis, olfactory performance was positively associated with cortical functional connectivity with the PCC in similar areas of attenuated cortical connectivity in PD‐L patients relative to PD‐H patients. On the other hand, the cortical functional connectivity with the caudate was negatively correlated with olfactory performance in similar areas of increased connectivity in PD‐L patients relative to PD‐H patients. The present study demonstrated that resting state functional connectivity exhibits a distinctive pattern depending on olfactory performance, which might shed light on a meaningful relationship between olfactory impairment and cognitive dysfunction in PD. Hum Brain Mapp 36:1716–1727, 2015. © 2014 Wiley Periodicals, Inc.     

Differentiation of Parkinsonism-Predominant Multiple System Atrophy from Idiopathic Parkinson Disease Using 3T Susceptibility-Weighted MR Imaging,Focusing on Putaminal Change and Lesion Asymmetry

BACKGROUND AND PURPOSE:Asymmetric presentation of clinical feature in parkinsonism is common, but correlatable radiologic feature is not clearly defined. Our aim was to evaluate 3T susceptibility-weighted imaging findings for differentiating parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease, focusing on putaminal changes and lesion asymmetry.MATERIALS AND METHODS:This retrospective cohort study included 27 patients with parkinsonism-predominant multiple system atrophy and 50 patients with idiopathic Parkinson disease diagnosed clinically. Twenty-seven age-matched subjects without evidence of movement disorders who underwent SWI were included as the control group. A consensus was reached by 2 radiologists who visually assessed SWI for the presence of putaminal atrophy and marked signal hypointensity on each side of the posterolateral putamen. We also quantitatively measured putaminal width and phase-shift values.RESULTS:The mean disease duration was 4.7 years for the patients with parkinsonism-predominant multiple system atrophy and 7.8 years for the patients with idiopathic Parkinson disease. In the patients with parkinsonism-predominant multiple system atrophy, putaminal atrophy was frequently observed (14/27, 51.9%) and was most commonly found in the unilateral putamen (13/14). Marked signal hypointensity was observed in 12 patients with parkinsonism-predominant multiple system atrophy (44.4%). No patients with idiopathic Parkinson disease or healthy controls showed putaminal atrophy or marked signal hypointensity. Quantitatively measured putaminal width, phase-shift values, and the ratio of mean phase-shift values for the dominant and nondominant sides were significantly different between the parkinsonism-predominant multiple system atrophy group and the idiopathic Parkinson disease and healthy control groups (P < .001).CONCLUSIONS:3T SWI can visualize putaminal atrophy and marked signal hypointensity in patients with parkinsonism-predominant multiple system atrophy with high specificity. Furthermore, it clearly demonstrates the dominant side of putaminal changes, which correlate with the contralateral symptomatic side of patients.

Parkinsonism-predominant multiple system atrophy (MSA-p) is one of the Parkinson-plus syndromes that has a clinical manifestation similar to that of idiopathic Parkinson disease (IPD) and is often challenging to diagnose in its early stage. MR imaging plays a role in differentiating MSA-p from IPD and is included as an additional feature for the diagnosis of possible multiple system atrophy.¹ Various conventional and functional MR imaging findings regarding the putamen in MSA-p have been reported.^2–6 However, these findings had limited sensitivity and specificity.⁶An asymmetric presentation of clinical features is common for IPD in its early stage, while symmetric symptoms are more common in MSA-p than in IPD.^7,8 However, the clinical manifestation of parkinsonism develops asymmetrically in many patients with MSA-p, and it has been reported that approximately 40%–50% of patients with MSA-p present with initial asymmetric symptoms.^8,9 This presentation increases the difficulty of clinically differentiating IPD from MSA-p in the early stage of disease. However, to our knowledge, there are few previous reports that used imaging to examine the asymmetry of putaminal abnormalities in MSA-p.Susceptibility-weighted imaging (SWI), which was recently introduced and is now widely used in clinical brain imaging, reflects the physical magnetic properties of tissues because susceptibility changes in tissues, such as iron deposition, are very sensitive.¹⁰ In addition to the sensitivity of SWI to paramagnetic material, corrected phase images that are calculated to form final SWI can provide quantitative phase-shift values that reflect tissue iron content.¹¹ Recently published studies attempted to use SWI to differentiate movement disorders, including MSA-p,¹² and demonstrated different iron-deposition patterns between MSA-p and IPD by measuring phase-shift values by using corrected phase images of SWI sequences.¹³ However, most previous studies regarding SWI were performed on 1.5T or weaker main magnetic field MR imaging machines. When main magnetic field is increased to 3T, spins process at a higher frequency, which may result in phase shifts caused by susceptibility changes being more exaggerated on SWI.Thus, the purpose of the present study was to evaluate the imaging findings of 3T SWI for differentiating MSA-p from IPD, focusing on putaminal changes and lesion asymmetry.     

Evaluation of Selective Arterial Embolization Effect by Chitosan Micro-Hydrogels in Hindlimb Sarcoma Rodent Models Using Various Imaging Modalities

Purpose

Embolization is mainly used to reduce the size of locally advanced tumors. In this study, selective arterial catheterization with chitosan micro-hydrogels (CMH) into the femoral artery was performed and the therapeutic effect was validated using different imaging methods.

Methods

Male SD rats (n = 18, 6 weeks old) were randomly assigned into three groups: Group 1 as control, Group 2 without any ligation of distal femoral artery, and Group 3 with temporary ligation of the distal femoral artery. RR1022 sarcoma cell lines were inoculated into thigh muscle. After 1 week, CMH was injected into the proximal femoral artery. Different imaging modalities were performed during a 3-week follow-up.

Results

The tumor size was significantly (P < 0.001) decreased in both Group 2 and Group 3 (P < 0.001) after selective arterial embolization therapy. ¹⁸F-FDG-PET/CT revealed decreased intensity of ¹⁸F-FDG uptake in tumors. The accumulation status of ¹²⁵I-CMH near the tumor was verified by gamma camera.

Conclusions

Appropriate selective arterial embolization therapy with CMH was.     

Anti-inflammatory,Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.

The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin E₂ (PGE₂), and proinflammatory cytokine (IL-1β , IL-6, and IL-10) production. Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, (91.0±3.2%), similar to α-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases.