CNS Neuroscience & Therapeutics最新文献

{"title":"mGluR1/IP3/ERK signaling pathway regulates vestibular compensation in ON UBCs of the cerebellar flocculus","authors":"Dan Liu,&nbsp;Jun Wang,&nbsp;E. Tian,&nbsp;Jingyu Chen,&nbsp;Weijia Kong,&nbsp;Yisheng Lu,&nbsp;Sulin Zhang","doi":"10.1111/cns.14419","DOIUrl":"10.1111/cns.14419","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the role of mGluR1α in cerebellar unipolar brush cells (UBC) in mediating vestibular compensation (VC), using mGluR1α agonist and antagonist to modulate ON UBC neurons, and explore the mGluR1/IP3/extracellular signal-regulated kinase (ERK) signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, AAV virus that knockdown ON UBC (mGluR1α) were injected into cerebellar UBC by stereotactic, and verified by immunofluorescence and western blot. The effect on VC was evaluated after unilateral labyrinthectomy (UL). Second, saline, (RS)-3,5-dihydroxyphenylglycine (DHPG), and LY367385 were injected into tubes implanted in rats at different time points after UL separately. The effect on ON UBC neuron activity was evaluated by immunofluorescence. Then, Phosphoinositide (PI) and p-ERK1/2 levels of mGluR1α were analyzed by ELISA after UL. The protein levels of p-ERK and total ERK were verified by western blot. In addition, the effect of mGluR1α activation or inhibition on VC-related behavior was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>mGluR1α knockdown induced VC phenotypes. DHPG increased ON UBC activity, while LY367385 reduced ON UBC activity. DHPG group showed an increase in PI and p-ERK1/2 levels, while LY367385 group showed a decrease in PI and p-ERK1/2 levels in cerebellar UBC of rats. The western blot results of p-ERK and total ERK confirm and support the observations. DHPG alleviated VC-related behavior phenotypes, while LY367385 exacerbated vestibular decompensation-like behavior induced by UL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>mGluR1α activity in cerebellar ON UBC is crucial for mediating VC through the mGluR1/IP3/ERK signaling pathway, which affects ON UBC neuron activity and contributes to the pathogenesis of VC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PGAM5 knockout causes depressive-like behaviors in mice via ATP deficiency in the prefrontal cortex","authors":"Weiwei Cui,&nbsp;Chunhui Chen,&nbsp;Liya Gong,&nbsp;Junyan Wen,&nbsp;Shanshan Yang,&nbsp;Min Zheng,&nbsp;Baogui Gao,&nbsp;Junxiong You,&nbsp;Xuecong Lin,&nbsp;Yanyu Hao,&nbsp;Zhimin Chen,&nbsp;Ziqi Wu,&nbsp;Liaoming Gao,&nbsp;Jiayu Tang,&nbsp;Zhen Yuan,&nbsp;Xuegang Sun,&nbsp;Linlin Jing,&nbsp;Ge Wen","doi":"10.1111/cns.14377","DOIUrl":"10.1111/cns.14377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Our study aimed to investigate how deficiency of PGAM5-mediated depressive behavior.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We firstly discovered that PGAM5 knockout (<i>PGAM5</i>^{<i>−/−</i>}) mice generated depressive-like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)-induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex <b>(</b>PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in <i>PGAM5</i>^{<i>−/−</i>} mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F₁F₀ synthase without influencing the interaction between ATP F₁F₀ synthase and Bcl-xl. We then conducted ATP administration to <i>PGAM5</i>^{<i>−/−</i>} mice and found that ATP could rescue the behavioral and neuronal phenotypes of <i>PGAM5</i>^{<i>−/−</i>} mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings provide convincing evidence that PGAM5 ablation generates depressive-like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stromal cell-derived factor-1 downregulation contributes to neuroprotection mediated by CXC chemokine receptor 4 interactions after intracerebral hemorrhage in rats","authors":"Yu Wu,&nbsp;Zhuwei Zhang,&nbsp;Xiaoou Sun,&nbsp;Jing Wang,&nbsp;Haitao Shen,&nbsp;Xue Sun,&nbsp;Zhong Wang","doi":"10.1111/cns.14400","DOIUrl":"10.1111/cns.14400","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) have a substantial role in neuronal formation, differentiation, remodeling, and maturation and participate in multiple physiological and pathological events. In this study, we investigated the role of SDF-1/CXCR4 in neural functional injury and neuroprotection after intracerebral hemorrhage (ICH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Western blot, immunofluorescence and immunoprecipitation were used to detect SDF-1/CXCR4 expression and combination respectively after ICH. TUNEL staining, Lactate dehydrogenase assay, Reactive oxygen species assay, and Enzyme-linked immunosorbent assay to study neuronal damage; Brain water content to assay brain edema, Neurological scores to assess short-term neurological deficits. Pharmacological inhibition and genetic intervention of SDF-1/CXCR4 signaling were also used in this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ICH induced upregulation of SDF-1/CXCR4 and increased their complex formation, whereas AMD3100 significantly reduced it. The levels of TNF-α and IL-1β were significantly reduced after AMD3100 treatment. Additionally, AMD3100 treatment can alleviate neurobehavioral dysfunction of ICH rats. Conversely, simultaneous SDF-1/CXCR4 overexpression induced the opposite effect. Moreover, immunoprecipitation confirmed that SDF-1/CXCR4 combined to initiate neurodamage effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study indicated that inhibition of SDF-1/CXCR4 complex formation can rescue the inflammatory response and alleviate neurobehavioral dysfunction after ICH. SDF-1/CXCR4 may have applications as a therapeutic target after ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10116439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The restoration ability of a short nap after sleep deprivation on the brain cognitive function: A dynamic functional connectivity analysis","authors":"Ziliang Xu,&nbsp;Yingjuan Chang,&nbsp;Fan Guo,&nbsp;Chen Wang,&nbsp;Na Chai,&nbsp;Minwen Zheng,&nbsp;Peng Fang,&nbsp;Yuanqiang Zhu","doi":"10.1111/cns.14413","DOIUrl":"10.1111/cns.14413","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The brain function impairment induced by sleep deprivation (SD) is temporary and can be fully reversed with sufficient sleep. However, in many cases, long-duration recovery sleep is not feasible. Thus, this study aimed to investigate whether a short nap after SD is sufficient to restore brain function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The data of 38 subjects, including resting state functional magnetic resonance imaging data collected at three timepoints (before SD, after 30 h of SD, and after a short nap following SD) and psychomotor vigilance task (PVT) data, were collected. Dynamic functional connectivity (DFC) analysis was used to evaluate changes in brain states among three timepoints, and four DFC states were distinguished across the three timepoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Before SD, state 2 (a resting-like FC matrix) was dominant (48.26%). However, after 30 h SD, the proportion of state 2 dramatically decreased, and state 3 (still resting-like, but FCs were weakened) became dominant (40.92%). The increased proportion of state 3 positively correlated with a larger PVT “lapse” time. After a nap, the proportions of states 2 and 3 significantly increased and decreased, respectively, and the change in proportion of state 2 negatively correlated with the change in PVT “lapse” time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, the results indicated that, after a nap, the cognitive function impairment caused by SD may be reversed to some extent. Additionally, DFC differed among timepoints, which was also associated with the extent of cognitive function impairment after SD (state 3) and the extent of recovery therefrom after a nap (state 2).</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of this speculation is needed before the possible beneficial effect of the ketogenic diet can be attributed to the increase in wild-type mtDNA","authors":"Josef Finsterer","doi":"10.1111/cns.14417","DOIUrl":"10.1111/cns.14417","url":null,"abstract":"&lt;p&gt;We read with interest the article by He et al. on a 20-year-old woman with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome due to the variant m.3243A&gt;G (heteroplasmy rate 55%) who benefited from the ketogenic diet (KD) over a period of 3 years with a break after 2.7 years.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Features that improved over this period included severity and frequency of seizures, frequency of stroke-like episodes (SLEs), headache, vision, hearing, gastrointestinal symptoms, and exercise intolerance.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; It was concluded that KD should not be interrupted but continued for life.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The study is compelling but has limitations that should be discussed.&lt;/p&gt;&lt;p&gt;A limitation of the study is the design. Since the validity of case reports is limited, the results cannot be easily generalized and must be confirmed by randomized and controlled studies. Although other case studies have also shown a positive effect of KD in MELAS,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; it still remains uncertain whether the positive effect is random or generalizable. Therefore, it is desirable that these preliminary results be confirmed by more substantiated studies on large, homogenous cohorts.&lt;/p&gt;&lt;p&gt;The authors speculate that improvement in the index patient was due to an increase in the amount of wild-type mtDNA but do not provide any evidence that the amount of wild-type mtDNA really increased in the index patient during the KD.&lt;/p&gt;&lt;p&gt;Compliance with KD was monitored by measuring serum levels of ketone bodies. Figure 2 shows 43 measurements, i.e. about one per month.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Did the clinical monitoring also ensure that the patient was complying with the KD in the 4 weeks prior to blood collection?&lt;/p&gt;&lt;p&gt;Because the reference limits for serum ketone bodies are missing, it cannot be assessed whether the reported values were within or outside the normal range throughout the KD.&lt;/p&gt;&lt;p&gt;The patient experienced a fifth SLE coinciding with discontinuation (non-compliance) of KD at 2.7 years after initiation.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This suggests that stopping KD may trigger the development of SLE. We should know whether KD cessation was indeed temporarily linked to the fifth SLE and what alternative triggers of the fifth SLE, such as seizures, infection, psychological or physical stress, or new medications, have been ruled out.&lt;/p&gt;&lt;p&gt;For seizures, the patient had been on oxcarbazepine since she was 13 and multiple anti-seizure drugs (ASDs) since she was 16.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Because some of the ASDs can be mitochondrion-toxic, particularly barbiturates, phenytoin, valproate, carbamazepine, and zonisamide,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; it is important to know which ASDs were actually administered and what dosage. It should also be discussed whether reducing ASDs after initiation of KD contributed to the positive effect of KD. It should also be mentioned whether low or high-calorie KD was","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"29 12","pages":"4175-4176"},"PeriodicalIF":5.5,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ofatumumab for the treatment of refractory anti-LGI1 encephalitis with long-term poor blood glucose control in type 1 diabetes","authors":"Kaili Chen,&nbsp;Le Yang,&nbsp;Lei Xu,&nbsp;Yan Jiang,&nbsp;Jinting He","doi":"10.1111/cns.14416","DOIUrl":"10.1111/cns.14416","url":null,"abstract":"&lt;p&gt;Ofatumumab (OFA) has been approved for the treatment of multiple sclerosis, works by depleting B lymphocytes, and has shown positive results.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Ofatumumab, a recombinant human monoclonal immunoglobulin G1 antibody that binds to B-cell expressed human CD20, may have potential in the treatment of autoimmune encephalitis and type 1 diabetes. We report a rare case of refractory anti-LGI1 encephalitis with long-term poor blood glucose control in a patient with type 1 diabetes. After OFA treatment (20 mg/time), we found that CD20&lt;sup&gt;+&lt;/sup&gt; and CD19&lt;sup&gt;+&lt;/sup&gt; lymphocytes were depleted, as well as a significant improvement in cognition, excessive daytime drowsiness and blood glucose levels, no further hyponatremia, and no significant adverse effects. Thus, our study suggests that OFA is effective and safe as a novel anti-CD20 monoclonal antibody for the treatment of refractory anti-LGI1 encephalitis with long-term poor blood glucose control in type 1 diabetes.&lt;/p&gt;&lt;p&gt;A 62-year-old man was admitted in July 2022, with presenting symptoms of episodic convulsions, memory decline, and excessive daytime drowsiness 3 months prior to admission. Two seizures occurred within 2 weeks before he was admitted to the hospital; the seizures manifested as involuntary twitching of his right hand, which lasted approximately 3–5 s, followed by flexion of both upper limbs, ankylosis of both lower limbs, unconsciousness, and upward movement of the eyes, which lasted for approximately 5 min. He was previously healthy, with no history of any disease except type 1 diabetes and no family history of inherited diseases. Initial examination showed drowsiness, impaired consciousness, and mixed-type aphasia, with a Modified Rankin Scale (mRS) score of 4, a Mini-Mental State Examination (MMSE) score of 2/30, and a Montreal Cognitive Assessment (MoCA) score of 2/30. Brain MRI demonstrated dotted and lamellar abnormal signals in the left frontal lobe, with a low signal in T1, high signal in T2, and high signal in T2 Flair images (Figure 1A). Laboratory examination revealed a positive result for sodium (123.4 mmol/L), fasting blood glucose (FBG) 10.40 mmol/L, glycosylated hemoglobin 9.5%, urine ketone bodies 1+, and C-peptide level &lt;0.20 ng/mL. Tests for antileucine-rich glioma inactivated 1 (anti-LGI-1) antibody were positive in CSF (titer 1:10) and serum (titer 1:10) samples. Blood pressure, electrocardiogram, bilateral cervical vascular ultrasound, cardiac ultrasound, and arteriovenous ultrasound of the extremities did not show any significant abnormalities. Genetic testing was performed on the patient and his son; whole-exome sequencing revealed that the patient was an HLA DRB1*07:01 carrier, while the susceptibility genes of theirs associated with type 1 diabetes were negative. Based on these findings, he was diagnosed with anti-LGI1 encephalitis with type 1 diabetes.&lt;/p&gt;&lt;p&gt;After a total of five repeated rounds of immunoglobulin treatment, no significa","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"29 12","pages":"4172-4174"},"PeriodicalIF":5.5,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10034602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MKP-1 regulates the inflammatory activation of microglia against Alzheimer's disease","authors":"Junhua Li,&nbsp;Lin Wang,&nbsp;Qinhua Zeng,&nbsp;Jing He,&nbsp;Qing Tang,&nbsp;Kejian Wang,&nbsp;Guiqiong He","doi":"10.1111/cns.14409","DOIUrl":"10.1111/cns.14409","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia in elderly people. Microglia-mediated neuroinflammation plays an important role in AD pathogenesis, so modulation of neuroinflammation has emerged as an essential therapeutic method to improve AD. The current study aims to investigate whether MKP-1 can regulate microglia phenotype and inflammatory factor release in AD and explore its possible mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Amyloid precursor protein/PS1 double transgenic mice and wild-type mice were selected to study the locations of microglia and amyloid-β (Aβ) plaques in different regions of mice brains. Changes in MKP-1 of microglia were detected using AD model mice and AD model cells. Changes in phenotype and the release of inflammatory factors within immortalized BV2 murine microglia were investigated by regulating the expression of MKP-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The distribution of microglia and Aβ plaques in the AD brain was region-specific. MKP-1 expression was downregulated in AD mice, and in vitro, with increasing Aβ concentrations, MKP-1 expression was reduced. MKP-1 over-expression increased M2 microglia but decreased M1 microglia accompanied by changes in inflammatory factors and inhibition of MKP-1 yielded the opposite result.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MKP-1 regulated microglia phenotype and inflammatory factor release in AD through modulation of the p38 signaling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10034604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The value of FDG combined with PiB PET in the diagnosis of patients with cognitive impairment in a memory clinic","authors":"Fang Liu,&nbsp;Yudi Shi,&nbsp;Qiuyan Wu,&nbsp;Huifeng Chen,&nbsp;Ying Wang,&nbsp;Li Cai,&nbsp;Nan Zhang","doi":"10.1111/cns.14418","DOIUrl":"10.1111/cns.14418","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To analyze the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with amyloid PET in cognitive impairment diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 187 patients with dementia or mild cognitive impairment (MCI) who underwent ¹¹C-Pittsburgh compound B (PiB) and FDG PET scans in a memory clinic were included in the final analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amyloid-positive and amyloid-negative dementia patient groups showed a significant difference in the proportion of individuals presenting temporoparietal cortex (<i>p</i> &lt; 0.001) and posterior cingulate/precuneus cortex (<i>p</i> &lt; 0.001) hypometabolism. The sensitivity and specificity of this hypometabolic pattern for identifying amyloid pathology were 72.61% and 77.97%, respectively, in patients clinically diagnosed with AD and 60.87% and 76.19%, respectively, in patients with MCI. The initial diagnosis was changed in 32.17% of patients with dementia after considering both PiB and FDG results. There was a significant difference in both the proportion of patients showing the hypometabolic pattern and PiB positivity between dementia conversion patients and patients with a stable diagnosis of MCI (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Temporoparietal and posterior cingulate/precuneus cortex hypometabolism on FDG PET suggested amyloid pathology in patients with cognitive impairment and is helpful in diagnostic decision-making and predicting AD dementia conversion from MCI, particularly when combined with amyloid PET.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal synaptic plasticity injury mediated by SIRT1 downregulation is involved in chronic pain-related cognitive dysfunction","authors":"Yanping Liu,&nbsp;Qiang Liu,&nbsp;Haibi Wang,&nbsp;Yongkang Qiu,&nbsp;Jiatao Lin,&nbsp;Weifeng Wu,&nbsp;Ning Wang,&nbsp;Wei Dong,&nbsp;Jie Wan,&nbsp;Chen Chen,&nbsp;Shuai Li,&nbsp;Hui Zheng,&nbsp;Yuqing Wu","doi":"10.1111/cns.14410","DOIUrl":"10.1111/cns.14410","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cognitive dysfunction associated with chronic pain may be caused by impaired synaptic plasticity. Considering the impact of silent information regulator 1 (SIRT1) on synaptic plasticity, we explored the exact role of SIRT1 in cognitive impairment caused by chronic pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the memory ability of mice with the fear conditioning test (FCT) after spared nerve injury (SNI) model. Western blotting and immunofluorescence were used to analyze the expression levels of SIRT1. Hippocampal synaptic plasticity was detected with Golgi staining, transmission electron microscopy, and long-term potentiation (LTP). In the intervention study, AAV9-CaMKIIα-Cre-EGFP was injected to SIRT1^flox/flox mice to knockdown the expression levels of SIRT1. Besides, SNI mice were injected with AAV2/9-CaMKIIα-SIRT1-3*Flag-GFP or SRT1720 to increase the expression levels or enzymatic activity of SIRT1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our current results indicated that cognitive function in SNI mice was impaired, SIRT1 expression in glutaminergic neurons in the hippocampal CA1 area was downregulated, and synaptic plasticity was altered. Selective knockdown of SIRT1 in hippocampus damaged synaptic plasticity and cognitive function of healthy mice. In addition, the impaired synaptic plasticity and cognitive dysfunction of SNI mice could be improved by the upregulation of SIRT1 expression or enzyme activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Reduced SIRT1 expression in hippocampus of SNI mice may induce cognitive impairment associated with chronic pain by mediating the impaired synaptic plasticity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10374698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extension domain of amyloid processor protein inhibits amyloidogenic cleavage and balances neural activity in a traumatic brain injury mouse model","authors":"Zhenxing Xie,&nbsp;Tianyu Li,&nbsp;Wei Su,&nbsp;Yanyun Lou,&nbsp;Yongsheng Zhang,&nbsp;Xiyuan Zhou,&nbsp;Zhanfei Li,&nbsp;Xiangjun Bai,&nbsp;Xinghua Liu","doi":"10.1111/cns.14402","DOIUrl":"10.1111/cns.14402","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mechanisms underlying cognitive dysfunction following traumatic brain injury (TBI) partially due to abnormal amyloid processor protein (APP) cleavage and neural hyperactivity. Binding of the extension domain of APP (ExD17) to the GABAbR1 receptor results in reduced neural activity, which might play a role in the mechanisms of cognitive dysfunction caused by TBI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Stretch-induced injury was utilized to establish a cell injury model in HT22 cells. The TBI model was created by striking the exposed brain tissue with a free-falling weight. Topical or intraperitoneal administration of ExD17 was performed. Cell viability was assessed through a cell counting kit-8 assay, while intracellular Ca²⁺ was measured using Fluo-4. Western blotting was used to investigate the expression of APP amyloidogenic cleavage proteins, GABAbR1, phospholipase C (PLC), PLCB3, and synaptic proteins. ELISA was performed to analyze the levels of Aβ42. Seizures were assessed using electroencephalography (EEG). Behaviors were evaluated through the novel object recognition test, open field test, elevated plus maze test, and nest-building test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ExD17 improved cell viability and reduced intracellular calcium in the cell injury model. The treatment also suppressed the increased expression of APP amyloidogenic cleavage proteins and Aβ42 in both cell injury and TBI models. ExD17 treatment reversed the abnormal expression of GABAbR1, GRIA2, p-PLCG1/PLCG1 ratio, and p-PLCB3/PLCB3 ratio. In addition, ExD17 treatment reduced neural activity, seizure events, and their duration in TBI. Intraperitoneal injection of ExD17 improved behavioral outcomes in the TBI mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ExD17 treatment results in a reduction of amyloidogenic APP cleavage and neuroexcitotoxicity, ultimately leading to an improvement in the behavioral deficits observed in TBI mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}