Diabetes mellitus type 2 as an underlying,comorbid or consequent state of mental disorders

Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice. Various factors contribute to the development of mental and somatic disorders. Type 2 diabetes mellitus (T2DM) is a significant health burden worldwide, and the prevalence of diabetes in adults is increasing. The comorbidity of diabetes and mental disorders is very common. By sharing a bidirectional link, both T2DM and mental disorders influence each other in various manners, but the exact mechanisms underlying this link are not yet elucidated. The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction, oxidative stress, endothelial dysfunction, and metabolic disturbances. Moreover, diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetes-associated cognitive decline to pre-dementia and dementia. A complex re-lationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production. The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders, emphasizing their complexity and interweaving. We also focused on the cognitive performances and changes in neurodegenerative disorders. The importance of implementing integrated approaches in treating both of these states is highlighted, along with the need for individual therapeutic strategies.     

Microorganismos relacionados con un mayor riesgo de presentar la enfermedad de Parkinson

Parkinson's disease is a neurodegenerative disorder that affects more than 7 million people worldwide. Its aetiology is unknown, although the hypothesis of a genetic susceptibility to environmental agents is accepted. These environmental agents include fungi, bacteria, and viruses. Three microorganisms are directly associated with a significantly increased risk of developing Parkinson's disease: the fungal genus Malassezia, the bacterium Helicobacter pylori, and the hepatitis C virus. If the host is vulnerable due to genetic susceptibility or immune weakness, these microorganisms can access and infect the nervous system, causing chronic neuroinflammation with neurodegeneration. Other microorganisms show an epidemiological association with the disease, including the influenza type A, Japanese encephalitis type B, St Louis, and West Nile viruses. These viruses can affect the nervous system, causing encephalitis, which can result in parkinsonism. This article reviews the role of all these microorganisms in Parkinson's disease.     

Impact of levetiracetam on cognitive impairment,neuroinflammation, oxidative stress,and neuronal apoptosis caused by lipopolysaccharides in rats

IntroductionNeuroinflammation is associated with the elevation of toxic proinflammatory mediators that promote neurodegeneration and subsequently affect cognition. Causes of inflammation in the neuronal cells are believed to initiate various neurodegenerative disorders, mainly Alzheimer’s disease. Levetiracetam is a second-generation antiepileptic drug. There is evidence supporting the memory-enhancing effect of levetiracetam from numerous experimental and clinical studies. Therefore, this research focused on finding its protective effects against lipopolysaccharides prompted cognitive impairment and exploring possible mechanisms underlining their neuroprotection.MethodologyTwo doses (100 or 200 mg/kg) of levetiracetam were administrated orally for 30 days. Additionally, four doses (250 µg/kg) of lipopolysaccharide were injected peripherally to induce neurotoxicity. Behavioral tests were carried out using various maze models. At the end of the tests, brain tissues were collected for biochemical evaluations. Cholinergic, neuroinflammatory, apoptosis, and oxidative-related parameters were analyzed in the brain homogenate to explore the possible mechanisms of action of levetiracetam.ResultsIn lipopolysaccharide-induced rats, levetiracetam indicated a reduction (p < 0.01) in transfer latency using the elevated plus-maze. An improvement (p < 0.01) in novel and familiar objects exploration time using novel object recognition test. A rise (p < 0.05) in novel arm entries and extended time spent in the novel arm using the Y-maze test. In extension, the levels of acetylcholine (p < 0.001), anti-inflammatory factors (transforming growth factor-β1; p < 0.01 and interleukin-10; p < 0.05), and an antioxidant (catalase; p < 0.01) were elevated in lipopolysaccharide-induced rats after the administration of levetiracetam. In contrast, inflammatory factors (cyclooxygenase-2; p < 0.05, nuclear factor kappa B; p < 0.05, tumor necrosis factor-α; p < 0.01, and interleukin-6 (p < 0.01), apoptosis inducers (BCL2-associated X protein; p < 0.05 and Caspase-3 (p < 0.001), and oxidative stress (malondialdehyde; p < 0.05) were considerably reduced with levetiracetam in lipopolysaccharide-induced rats.ConclusionThe collective results suggested that levetiracetam may be able to treat neuroinflammatory-related memory loss by enhancing cholinergic activity while reducing neuroinflammation, cellular apoptosis, and oxidative stress.     

右美托咪定抑制NF-κB核易位减轻大鼠创伤性脑损伤神经炎症北大核心CSCD

目的探究右美托咪定(dexmedetomidine,DEX)调节创伤性脑损伤(traumatic brain injury,TBI)后小胶质细胞(microglial,MG)极化及神经炎症的机制。方法42只成年雄性SD大鼠按随机数字表法分为假手术组(sham组)、TBI组、TBI+DEX组(又分为治疗1 d、3 d和7 d组)、TBI+NF-κB抑制剂(pyrrolidine dithiocarbamate,PDTC)组和TBI+DEX+PDTC组,每组6只。采用改良Feeney自由落体法制备大鼠TBI模型,造模后1 h腹腔注射PDTC 100 mg/kg、2 h腹腔注射DEX 100μg/kg,直至取材。于取材前采用改良的神经功能缺损评分法(modified neurological severity score,mNSS)评价大鼠神经功能,ELISA检测血清炎症因子,取大鼠损伤皮质通过Western Blot检测MG M1和M2表型标记物及MyD88、NF-κB p65蛋白表达,免疫荧光染色观察损伤皮质处NF-κB p65在MG中的表达及入核情况。计量资料多组间比较采用单因素及双因素方差分析。结果与Sham组相比,TBI组mNSS评分显著升高,DEX组mNSS评分明显低于TBI组,差异有统计学意义(P<0.05);ELISA和Western Blot检测TBI组血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白介素(interleukin,IL)-1β水平及MG M1表型标记物(IL-1β和TNF-α)升高,抗炎因子IL-10和M2型标记物(精氨酸酶-1和IL-10)表达下降(P<0.05);DEX降低血清TNF-α及IL-1β的水平,提高IL-10水平,并促进MG M2表型极化(P<0.05)。此外,DEX组MyD88表达下调,NF-κB p65核易位被抑制,该效应可被PDTC增强。结论DEX可通过抑制NF-κB核易位调节TBI大鼠MG活化,减轻神经炎症。     

瞬时受体电位香草酸亚型1在缺血性中风机制及相关中药的研究进展

中风是严重危害人民健康的重大疾病，居我国致死疾病之首，缺血性中风（IS）占70%以上。因时间窗窄、适应证严格等原因，静脉溶栓、血管内治疗临床实际受益人群极为有限，寻求特异性有效药物仍是临床迫切需求，深入探索相关机制、发掘治疗新靶点是创新药物研发的关键。近年来，瞬时受体电位香草酸亚型1（TRPV1）通过非谷氨酸机制调控中风后钙离子稳态，并参与中风后多种复杂机制，有望成为中风后神经保护作用的新兴靶点。中药具有多成分、多靶点的特点，已有临床研究证实在中风不同阶段应用中药治疗均有良好疗效，目前已在许多中药如吴茱萸、生姜、天然冰片中发现TRPV1激动剂/抑制剂。现从TRPV1参与调控钙超载、兴奋性毒性、神经炎症等病理机制出发，厘清其具体作用，并归纳可能作用于TRPV1治疗中风的中药成分，以期为中风研究及治疗提供新思路。     

Altered serum levels of platelet-derived growth factor receptor β and cluster of differentiation 13 suggest a role for pericytes in West syndrome

BackgroundPericytes play a role in the maintenance of the blood–brain barrier and neuroinflammation, attracting attention as to whether they are also involved in the pathogenesis of epilepsy. This study aimed to explore the relationship between West syndrome and pericytes.MethodsEighteen Japanese pediatric West syndrome patients and nine controls aged 2 years or younger were retrospectively enrolled in this study. We assessed the serum levels of pericyte markers, serum PDGFRβ (platelet-derived growth factor receptor β), CD13 (aminopeptidase N), and 27 cytokines in 17 pediatric patients with West syndrome and the control group.ResultsPatients with West syndrome exhibited significantly increased CD13 and decreased PDGFRβ levels, compared with controls but not serum cytokine levels. These values did not differ significantly between symptomatic and idiopathic West syndrome.ConclusionPericytes might be implicated in the pathogenesis of West syndrome.     

全身麻醉药物对发育大脑小胶质细胞影响的研究进展

近年来，全身麻醉药物对发育大脑的影响成为关注的焦点。全身麻醉药物可造成动物胎儿及幼崽随着生长发育出现短期及长期认知功能障碍，而临床中回顾性研究结果与动物实验结果尚不一致。因此，全身麻醉药物对发育大脑有无影响尚无统一定论。小胶质细胞作为中枢神经系统免疫细胞在发育的不同阶段表现不同形态，执行不同的功能，在神经元损伤修复、神经炎症、神经网络构建等方面发挥重要作用。本文将常用全身麻醉药物包括吸入麻醉药、静脉麻醉药、阿片类药物等对发育大脑小胶质细胞的影响机制做一综述。