Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model:mechanisms underlying orofacial allodynias and headache

Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

汉语认知研究与神经信息学

语言是人脑特有的功能,阐明语言的脑机制对揭示人脑的奥秘具有重要意义.汉语是中国的特色,是一种象形表意文字,具有很强的图形特征,在形、音、义加工方面与西方拼音文字有很大不同.国外对拼音文字的形、音、义加工的脑机制开展了大量研究,以往常采用认知心理学的方法,如反应时记录法、眼动记录法等,获得了大量的实验数据;或者运用临床研究方法,搜集失语证、语言障碍患者病案以发现规律.由于检测技术手段的局限,很难直接用于人脑功能的研究,一些关键问题仍未获得肯定的结论.不少学者认为,利用汉字的一些特点进行相应的研究,可能有助于澄清目前国际上关于言语加工机制中一些重要的争论.近年来,美国、日本、新加坡等国陆续开展了汉语认知研究.研究汉语认知就是研究人脑对汉语信息的加工、处理与整合机制,包括汉语信息的输入、储存、内部加工与提取和输出等过程,以揭示人脑的高级功能和奥秘.

Ca^(2+) Entry Through TRPC1 Channels Contributes to Intracellular Ca^(2+) Dynamics and Consequent Glutamate Release from Rat Astrocytes

各种不同的刺激作用于星型胶质细胞,可以导致胞浆内Ca2+浓度增加,进而释放更多谷氨酸作用于周边的神经元。大部分Ca2+来源于细胞内,小部分来源于细胞外。Ca2+内流是通过钙池操纵Ca2+通道(SOC)实现的。因此,作者观察在星型胶质细胞内Ca2+激活与谷氨酸释放过程中钙池操纵Ca2+通道(SOC)发挥了什么样的作用。已有研究显示星型胶质细胞所表达的TRPC通道(Ca2+通过瞬时受体电位通道相关蛋白)介导了钙池操纵Ca2+的内流。本文发现培养的星形胶质细胞以及从视皮质中新分离的星形胶质细胞表达TRPC1,TRPC4,和TRPC5。间接免疫组化显示这些蛋白存在于整个细胞中,然而机能检测TRPC1主要表达在质膜上。在新分离的星形胶质细胞中做标记,显示了在细胞发育过程中TRPC表达的改变。应用抗TRPC1的抗体,可以阻断TRPC1通道并且可以测定它们在培养的星形细胞的机械性和激动剂触发的钙离子内流过程中的作用。阻断TRPC1可以减少机械诱导的钙离子依赖性的谷氨酸盐的释放。这些实验数据表明,钙离子通过TRPC1通道的内流有助于钙离子在星形细胞中的信号传导以及由此引起的谷氨酸盐的释放。

Metal-Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications

Investigation of metal–organic frameworks(MOFs)for biomedical applications has attracted much attention in recent years.MOFs are regarded as a promising class of nanocarriers for drug delivery owing to well-defined structure,ultrahigh surface area and porosity,tunable pore size,and easy chemical functionalization.In this review,the unique properties of MOFs and their advantages as nanocarriers for drug delivery in biomedical applications were discussed in the first section.Then,state-ofthe-art strategies to functionalize MOFs with therapeutic agents were summarized,including surface adsorption,pore encapsulation,covalent binding,and functional molecules as building blocks.In the third section,the most recent biological applications of MOFs for intracellular delivery of drugs,proteins,and nucleic acids,especially aptamers,were presented.Finally,challenges and prospects were comprehensively discussed to provide context for future development of MOFs as efficient drug delivery systems.

Neuroendocrine,epigenetic,and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.

Nature can still be the strongest help against aging and neurodegeneration:the sirtuins way

Unfortunately,ag ing is not a reversible phenomenon and the processes of senescence are unavoidable.However,the biological effects of aging may be turned back,and with those,it can be reduced risk of all age-related illnesses,such as cardiovascular diseases,cancer,diabetes,and neurodegenerative diseases,including Alzheimer’s disease(AD),and Parkinson’s diseases(PD).In the latest decades,scientists worldwide therefore have developed several strategies,either natural or pharmacological,to counteract aging phenomena,with the final goal to improve human life expectancy.The main scientific rationale beyond these strategies focuses on the opportunity to reduce chronic low-grade inflammation(inflammaging),the increase in oxidative stress damage,and the impairment in the immune system,all typical mechanisms of senescence(Verdaguer et al.,2012).

Peripheral vestibular system: Age-related vestibular loss and associated deficits

Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision,cognition), it is important to examine the individual contributions of these factors with ARVL. While therelationship between the vestibular and visual systems has been well studied (Bronstein et al., 2015),little is known about the association of the peripheral vestibular system with neurodegenerative disorders (Cronin et al., 2017). Further, emerging research developments implicate the vestibular system asan opportunity for examining brain function beyond balance, and into other areas, such as cognition andpsychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide thedevelopment of integrated interventions for patients who remain at risk for decline. In this review, wewill discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relatesto neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, withan emphasis on improving care for patients with ARVL.

Clinical challenges in the ataxias

Ataxias are rare diseases and the etiologic heterogeneity make individual entities even rarer.There are still substantial numbers of patients who are still poorly understood.Available assessment techniques still point to large numbers of patients needed for clinical trials and the need for cooperative efforts,better assessment tools and novel trial designs.Better understanding of neural circuitry abnormalities may lead to more effective symptomatic therapy.Opportunities exist for targeting at risk individuals for effective therapies but how this can be done is not clear.Preventive strategies may become feasible in many ataxias.

2009年成瘾研究进展(英文)

在美国,每年有超过40万的人死于吸烟、暴饮暴食、物质滥用以及意外事故和自杀。此外,合并有精神疾病的成瘾者(双重诊断)相当普遍。约29%患有精神疾病的人和一半左右患严重精神疾病(如精神分裂症)的人有成瘾史。因此,成瘾相关的预防、研究及治疗依然是精神病学领域关注的重点。我们将回顾2008 -2009年在药物滥用、食物和其他成瘾方面的研究。在药物试验、药物的选择、成瘾易感性、干预的预后以及复吸的可能性方面存在明显的个体差异。在过去的几十年中,在成瘾的认定、预防和治疗方面取得的成绩是有目共睹的。例如,虽然直到DSM-ⅡI修订版出台才将可卡因列为有滥用潜力的物质,但这一发现拓展了以往局限于对成瘾躯体戒断症状的研究、治疗的范围。最近在动物模型方面已有所突破,目前正在进行有关成瘾大鼠的研究。此外,神经生物学、影像学、蛋白质组学、纳米技术、药理学以及行为科学研究方面的进展也对成瘾领域的研究产生影响。本文综述了我们在成瘾研究中的部分工作以及其他成瘾研究方面取得的进展。

TDP-35,a truncated fragment of TDP-43,induces dose-dependent toxicity and apoptosis in flies

TAR DNA-binding protein 43(TDP-43)is an essential 414 amino acid protein that regulates multiple aspects of RNA biogenesis,processing,and transport.It localizes primarily in the nucleus,but abnormal translocation and accumulation in the cytosol occur under pathological conditions(Tziortzouda et al.,2021).TDP-43 abnormalities are typical pathological hallmarks of amyotrophic lateral sclerosis(ALS)and frontotemporal lobar degeneration.Mutations in the TDP-43-encoding gene TARDBP cause familial ALS。

Hypothesizing “Reward” Gene Polymorphisms May Predict High Rates of Injury and Addiction in the Workforce: A Nutrient and Electrotherapeutic Based Solution

We hypothesize that individuals with genetic predisposition to Substance Use Disorder (SUD) may have greater likelihood of experiencing work related accidents. We further hypothesize that high risk populations will carry single or multiple polymorphisms associated with brain reward circuitry and/or brain reward cascade, including: Dopaminergic (i.e. DRD2 receptor genes);Serotonergic (i.e. 5-HTT2 receptor genes);Endorphinergic (i.e. pre-enkephalin genes);Gabergic (i.e. GABAA receptor genes);Neurotransmitter Metabolizing genes (i.e. MAO and COMT genes) among others (GARSRXTM). Analgesic addiction as well as “pseudoaddiction” must be treated to improve pain control and its management. We propose that non-pharmacological alternatives to pain relief, in high risk, addiction-prone individuals, are Electrotherapeutic Device(s) and Programs. We further propose patented KB220Z, a nutraceutical designed to release dopamine at the nucleus accumbens, will reduce craving behavior, in genetically programmed individuals. By utilizing both alternatives in DNA analyzed injured workers, a reduction in analgesic addiction (genuine or pseudo) leads to improved health and quicker return to work. We also hypothesize that this novel approach will impact costs related to injuries in the workforce. Effective management of chronic pain, especially in high addiction-prone workforce populations, is possible in spite of being particularly elusive. A series of factors encumber pain assessment and management, including analgesia addiction, pharmacogenomic response to pain medications, and genetically inherited factors involving gene polymorphisms. Additional research is required to test these stipulated hypotheses related to genetic proneness to addiction, but also proneness to accidents in the workplace and reduction of craving behavior. Our hypothesis that genotyping coupled with both KB220ZTM and the pharmaceutical-free Electrotherapy, will reduce iatrogenic induced analgesia addiction. This approach will achieve attainable effective pain management and quicker return to work. We propose outcomes such as the Reward Deficiency System SolutionTM may become an adjunct in the war against iatrogenic pain medication addiction.

Iatrogenic opioid dependence is endemic and legal: Genetic addiction risk score (GARS) with electrotherapy a paradigm shift in pain treatment programs

The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave? device. The primary effect of the H-Wave?device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.

拉莫三嗪和托吡酯对健康受试者认知功能和行为能力的影响

Background: The relative cognitive and behavioral effects of lamotrigine (LTG ) and topiramate (TPM) are unclear. Methods: The authors directly compared the c ognitive and behavioral effects of LTG and TPM in 47 healthy adults using a dou ble- blind, randomized crossover design with two 12- week treatment periods. D uring each treatment condition, subjects were titrated to receive either LTG or TPM at a target dose of 300 mg/day for each. Neuropsychological evaluation inclu ded 17 measures yielding 41 variables of cognitive function and subjective behav ioral effects. Subjects were tested at the end of each antiepileptic drug (AED) treatment period and during two drug- free conditions (pretreatment baseline an d 1 month following final AED withdrawal). Results: Direct comparison of the two AEDs revealed significantly better performance on 33 (80% ) variables for LTG, but none for TPM. Even after adjustment for blood levels, performance was bette r on 19 (46% ) variables for LTG, but none for TPM. Differences spanned both ob jective cognitive and subjective behavioral measures. Comparison of TPM to the n on- drug average revealed significantly better performance for non- drug avera ge on 36 (88% ) variables, but none for TPM. Comparison of LTG to non- drug av erage revealed better performance on 7 (17% ) variables for non- drug average and 4 (10% ) variables for LTG. Conclusions: Lamotrigine produces significantly fewer untoward cognitive and behavioral effects compared to topiramate (TPM) at the dosages, titrations, and timeframes employed in this study. The dosages emp loyed may not have been equivalent in efficacy. Future studies are needed to del ineate the cognitive and behavioral effects of TPM at lower dosages.

Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo enriched autologous T-lymphocytes in the treatment of children with primary brain tumors

The therapeutic approach of adoptive lymphocyte transfer (ALT) using lymphocytes primed and expanded ex-vivo by exposure to total tumor RNA (ttRNA) containing dendritic cells (DCs) and administered after lymphodepletive host conditioning in patients with refractory melanoma with brain metastases has shown excellent objective responses indicating that the central nervous system (CNS) is not an immune privileged site and further paved the way for utilization of a similar approach in other cancers. We have shown that the use of ALT + ttRNA DCs following either myeloablative or non-myeloablative host conditioning is feasible and safe and appears to prolong survival in a proportion of children with recurrent medulloblastoma who had failed standard cytotoxic therapy. Further refinements in this promising approach are needed to improve outcomes and extend this treatment to a broad range of CNS malignancies.

Bioconjugated Silica Nanoparticles: Development and Applications

Advanced bioanalysis,including accurate quantitation,has driven the need to understand biology and medicine at the molecular level.Bioconjugated silica nanoparticles have the potential to address this emerging challenge.Particularly intriguing diagnostic and therapeutic applications in cancer and infectious disease as well as uses in gene and drug delivery,have also been found for silica nanoparticles.In this review,we describe the synthesis,bioconjugation,and applications of silica nanoparticles in different bioanalysis formats,such as selective tagging,barcoding,and separation of a wide range of biomedically important targets.Overall,we envisage that further development of these nanoparticles will provide a variety of advanced tools for molecular biology,genomics,proteomics and medicine.

Gold nanorod-photosensitizer conjugate with extracellular pH-driven tumor targeting ability for photothermal/photodynamic therapy

Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.

Self-assembled multifunctional DNA nanoflowers for the circumvention of multidrug resistance in targeted anticancer drug delivery

Cancer chemotherapy has been limited by its side effects and multidrug resistance （MDR）, the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers （NFs） for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin （Dox）- binding DNA for drug delivery. NF sizes are tunable （down to N200 nm in diameter）, and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity （71.4%, wt/wt）. Although the Dox- loaded NFs （NF-Dox） are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.

Highly Fluorescent Dye-Doped Silica Nanoparticles Increase Flow Cytometry Sensitivity for Cancer Cell Monitoring

Early and accurate diagnosis and treatment of cancer depend on rapid,sensitive,and selective detection of tumor cells.Current diagnosis of cancers,especially leukemia,relies on histology and fl ow cytometry using single dye-labeled antibodies.However,this combination may not lead to high signal output,which can hinder detection,especially when the probes have relatively weak affi nities or when the receptor is expressed in a low concentration on the target cell surface.To solve these problems,we have developed a novel method for sensitive and rapid detection of cancer cells using dye-doped silica nanoparticles(NPs)which increases detection sensitivity in fl ow cytometry analyses between 10-and 100-fold compared to standard methods.Our NPs are~60 nm in size and can encapsulate thousands of individual dye molecules within their matrix.We have extensively investigated surface modifi cation strategies in order to make the NPs suitable for selective detection of cancer cells using fl ow cytometry.The NPs are functionalized with polyethylene glycol(PEG)to prevent nonspecifi c interactions and with neutravidin to allow universal binding with biotinylated molecules.By virtue of their reliable and selective detection of target cancer cells,these NPs have demonstrated their promising usefulness in conventional fl ow cytometry.Moreover,they have shown low background signal,high signal enhancement,and effi cient functionalization,either with antibody-or aptamer-targeting moieties.

Zinc-substituted hemoglobin with specific drug binding sites and fatty acid resistance ability for enhanced photodynamic therapy

Precisely designed protein-based nanodrugs, as a kind of colloidal drug system, have attracted significant attention in tumor therapy because of their refined drug loading ratio, controlled delivery efficacy and natural biocompatibility. However, most drugs are conjugated to the protein carriers randomly without specific binding sites. Moreover, such sites could easily be replaced by lipophilic molecules in the physiological environment and result in low delivery efficiency. With strong and specific binding locations especially comparatively narrow spatial binding sites and nonflexible structure, hemin (FePPIX)-free hemoglobin or apohemoglobin (apoHb), as a natural metalloporphyrin protein carrier, represents great potential in bioapplication. Therefore, we herein introduce a folate acid (FA) modified, zinc-substituted hemoglobin (ZnPHb-FA) as a naturally occurring protein matrix-based photosensitizer for cancer photodynamic therapy (PDT). Noncovalent inserted ZnPPIX molecules in apoHb possess an extremely stable property and significant recovered photoproperties with superior biocompatibility and phototoxicity, both in vitro and in vivo. This stability was verified by molecular docking analysis and calculation of binding constant, representing a total of five drug binding sites of apoHb for ZnPPIX molecules, four of which are energetically favorable (△G value of -11.9 kcal/mol), and one which is energetically acceptable (△G value of -9 kcal/mol). Folate acid modification has been shown to efficiently enhance the internalization and retention time of ZnPHb nanodrug. ZnPHb-FA is also an efficient depressor of hemin oxygenase-1 (HO-1), which could, in turn, lower the antioxidant ability of cancer cells by decreasing the production of biiirublin. Results in vitro and in vivo both indicated that the firmly combination of apoHb and ZnPPIX described here represents a novel and efficient protein nanodrug systems for cancer therapy.

Store-operated calcium entry in neuroglia

Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ excitability＂ of glia. In mammalian glial cells the major source of Ca^2＋ for this excitability is the lumen of the endoplasmic reticulum （ER）, which is ultimately （re）filled from the extracellular space. This occurs via store-operated Ca^2＋ entry （SOCE） which is supported by a specific signaling system connecting the ER with plasmalemmal Ca^2＋ entry. Here, emptying of the ER Ca^2＋ store is necessary and sufficient for the activation of SOCE, and without Ca^2＋ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca^2＋ sensors, such as stromal interaction molecule, and possibly ER Ca^2＋ pumps （of the SERCA type）. There are at least two sets of plasmalemmal channels mediating SOCE, the Ca2＊-release activated channels, Orai, and transient receptor potential （TRP） channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SOCE. In physiological conditions the SOCE pathway is instrumental for the sustained phase of the Ca^2＋ signal observed following stimulation of metabotropic receptors on glial cells.