Brain Cell Metabolism Research Articles

Molecular overlaps of neurological manifestations of COVID-19 and schizophrenia from a proteomic perspective.

COVID-19, a complex multisystem disorder affecting the central nervous system, can also have psychiatric sequelae. In addition, clinical evidence indicates that a diagnosis of a schizophrenia spectrum disorder is a risk factor for mortality in patients with COVID-19. In this study, we aimed to explore brain-specific molecular aspects of COVID-19 by using a proteomic approach. We analyzed the brain proteome of fatal COVID-19 cases and compared it with differentially regulated proteins found in postmortem schizophrenia brains. The COVID-19 proteomic dataset revealed a strong enrichment of proteins expressed by glial and neuronal cells and processes related to diseases with a psychiatric and neurodegenerative component. Specifically, the COVID-19 brain proteome enriches processes that are hallmark features of schizophrenia. Furthermore, we identified shared and distinct molecular pathways affected in both conditions. We found that brain ageing processes are likely present in both COVID-19 and schizophrenia, albeit possibly driven by distinct processes. In addition, alterations in brain cell metabolism were observed, with schizophrenia primarily impacting amino acid metabolism and COVID-19 predominantly affecting carbohydrate metabolism. The enrichment of metabolic pathways associated with astrocytic components in both conditions suggests the involvement of this cell type in the pathogenesis. Both COVID-19 and schizophrenia influenced neurotransmitter systems, but with distinct impacts. Future studies exploring the underlying mechanisms linking brain ageing and metabolic dysregulation may provide valuable insights into the complex pathophysiology of these conditions and the increased vulnerability of schizophrenia patients to severe outcomes.

Crosstalk Among Glial Cells in the Blood-Brain Barrier Injury After Ischemic Stroke.

Blood-brain barrier (BBB) is comprised of brain microvascular endothelial cells (ECs), astrocytes, perivascular microglia, pericytes, neuronal processes, and the basal lamina. As a complex and dynamic interface between the blood and the central nervous system (CNS), BBB is responsible for transporting nutrients essential for the normal metabolism of brain cells and hinders many toxic compounds entering into the CNS. The loss of BBB integrity following stroke induces tissue damage, inflammation, edema, and neural dysfunction. Thus, BBB disruption is an important pathophysiological process of acute ischemic stroke. Understanding the mechanism underlying BBB disruption can uncover more promising biological targets for developing treatments for ischemic stroke. Ischemic stroke-induced activation of microglia and astrocytes leads to increased production of inflammatory mediators, containing chemokines, cytokines, matrix metalloproteinases (MMPs), etc., which are important factors in the pathological process of BBB breakdown. In this review, we discussed the current knowledges about the vital and dual roles of astrocytes and microglia on the BBB breakdown during ischemic stroke. Specifically, we provided an updated overview of phenotypic transformation of microglia and astrocytes, as well as uncovered the crosstalk among astrocyte, microglia, and oligodendrocyte in the BBB disruption following ischemic stroke.

Type-1 cannabinoid receptors and their ever-expanding roles in brain energy processes.

The brain requires large quantities of energy to sustain its functions. At the same time, the brain is isolated from the rest of the body, forcing this organ to develop strategies to control and fulfill its own energy needs. Likely based on these constraints, several brain-specific mechanisms emerged during evolution. For example, metabolically specialized cells are present in the brain, where intercellular metabolic cycles are organized to separate workload and optimize the use of energy. To orchestrate these strategies across time and space, several signaling pathways control the metabolism of brain cells. One of such controlling systems is the endocannabinoid system, whose main signaling hub in the brain is the type-1 cannabinoid (CB1) receptor. CB1 receptors govern a plethora of different processes in the brain, including cognitive function, emotional responses, or feeding behaviors. Classically, the mechanisms of action of CB1 receptors on brain function had been explained by its direct targeting of neuronal synaptic function. However, new discoveries have challenged this view. In this review, we will present and discuss recent data about how a small fraction of CB1 receptors associated to mitochondrial membranes (mtCB1), are able to exert a powerful control on brain functions and behavior. mtCB1 receptors impair mitochondrial functions both in neurons and astrocytes. In the latter cells, this effect is linked to an impairment of astrocyte glycolytic function, resulting in specific behavioral outputs. Finally, we will discuss the potential implications of (mt)CB1 expression on oligodendrocytes and microglia metabolic functions, with the aim to encourage interdisciplinary approaches to better understand the role of (mt)CB1 receptors in brain function and behavior.

Ozone therapy for high-grade glioma: an overview.

High-grade gliomas (grades III and IV) are highly malignant and aggressive brain tumors that present significant treatment challenges. Despite advances in surgery, chemotherapy, and radiation therapy, the prognosis for patients with glioma remains poor, with a median overall survival (mOS) range of 9-12 months. Therefore, exploring new and effective therapeutic strategies to improve glioma prognosis is of utmost importance and ozone therapy is a viable option. Ozone therapy has been used in various cancers, such as colon, breast, and lung, yielding significant results in preclinical studies and clinical trials. Only a few studies have been conducted on gliomas. Furthermore, since the metabolism of brain cells involves aerobic glycolysis, ozone therapy may improve the oxygen condition and enhance glioma radiation treatment. However, understanding the correct ozone dosage and optimal time of administration remains challenging. Herein, we hypothesize that ozone therapy should be more effective in gliomas compared with other tumors. This study provides an overview of the use of ozone therapy in high-grade glioma, including mechanisms of action, preclinical data, and clinical evidence.

Effect of transcranial direct current stimulation on neurological injury markers and prognosis in patients with acute and severe carbon monoxide poisoning

Objective: To observe the effects of transcranial direct current stimulation (tDCS) on nerve injury markers and prognosis in patients with acute severe carbon monoxide poisoning (ASCOP) . Methods: In May 2021, 103 ASCOP patients were treated in the emergency department of Harrison International Peace Hospital of Hebei Medical University from November 2020 to January 2021. The patients were divided into two groups according to whether they received tDCS treatment. The control group (50 cases) were given oxygen therapy (hyperbaric oxygen and oxygen inhalation) , reducing cranial pressure, improving brain circulation and cell metabolism, removing oxygen free radicals and symptomatic support, and the observation group (53 cases) was treated with 2 weeks of tDCS intensive treatment on the basis of conventional treatment. All patients underwent at least 24 h bispectral index (BIS) monitoring, BIS value was recorded at the hour and the 24 h mean value was calculated. Neuron-specific enolase (NSE) and serum S100B calcium-binding protein (S100B) were detected after admission, 3 d, 7 d and discharge. Follow-up for 60 days, the incidence and time of onset of delayed encephalopathy (DEACMP) with acute carbon monoxide poisoning in the two groups were recorded. Results: The NSE and S100B proteins of ASCOP patients were significantly increased at admission, but there was no significant difference between the two groups (P=0.711, 0.326) . The NSE and S100B proteins were further increased at 3 and 7 days after admission. The increase in the observation group was slower than that in the control group, and the difference was statistically significant (P(3 d)=0.045, 0.032, P(7 d)=0.021, 0.000) ; After 14 days, it gradually decreased, but the observation group decreased rapidly compared with the control group, with a statistically significant difference (P=0.009, 0.025) . The 60 day follow-up results showed that the incidence of DEACMP in the observation group was 18.87% (10/53) , compared with 38.00% (19/50) in the control group (P=0.048) ; The time of DEACMP in the observation group[ (16.79±5.28) d] was later than that in the control group[ (22.30±5.42) d], and the difference was statistically significant (P=0.013) . Conclusion: The early administration of tDCS in ASCOP patients can prevent the production of NSE and S100B proteins, which are markers of nerve damage. and can improve the incidence and time of DEACMP.

Divergent Effect of Central Incretin Receptors Inhibition in a Rat Model of Sporadic Alzheimer's Disease.

The incretin system is an emerging new field that might provide valuable contributions to the research of both the pathophysiology and therapeutic strategies in the treatment of diabetes, obesity, and neurodegenerative disorders. This study aimed to explore the roles of central glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) on cell metabolism and energy in the brain, as well as on the levels of these incretins, insulin, and glucose via inhibition of the central incretin receptors following intracerebroventricular administration of the respective antagonists in healthy rats and a streptozotocin-induced rat model of sporadic Alzheimer’s disease (sAD). Chemical ablation of the central GIP receptor (GIPR) or GLP-1 receptor (GLP-1R) in healthy and diseased animals indicated a region-dependent role of incretins in brain cell energy and metabolism and central incretin-dependent modulation of peripheral hormone secretion, markedly after GIPR inhibition, as well as a dysregulation of the GLP-1 system in experimental sAD.

Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients

Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, the astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of “chronic stress” using human induced pluripotent stem cell (iPSC)-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. The MDD-specific DEGs are related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.

Role of ECM in the Brain‐Gut Connection

We sought to determine the role of extracellular matrix (ECM) proteoglycans on regulating brain function and cell metabolism. In the first series of studies, we used dietary fructose to perturbate metabolism based on evidence that fructose is a major contributor to the epidemic of diabetes and obesity. Our transcriptomic studies (Meng et al, EBiomed, 157(7), 2016) showed that the gene for the proteoglycan biglycan (Bgn) occupies a central position in a network of genes receptive to the action of fructose in the hypothalamus (main brain center of metabolic control). We pursued studies further and exposed male biglycan knockout mice (Bgn0/-) to fructose for 7 weeks, and results showed that the Bgn0/- gene perturbation compensated for a decrement in learning and memory performance in mice exposed to fructose (Ying et al., BBADIS, 1864(12) 2018). Learning and memory performance was consistent with an attenuation of the action of fructose on hippocampal plasticity markers CREB and BDNF. Bgn siRNA treatment abolished the effects of fructose on CREB and BDNF levels, in conjunction with reducing a fructose-related increase in Bgn protein. In addition, fructose consumption perturbed the systemic metabolism of glucose and lipids, that were also altered in the Bgn0/ mice. Transcriptomic profiling of hypothalamus, hippocampus, and liver supported the regulatory action of Bgn on key molecular pathways involved in metabolism, immune response, and neuronal plasticity. Overall results underscore the tissue-specific role of the extracellular matrix in the regulation of metabolism and brain function, and support Bgn as a key modulator of the impact of fructose across body and brain. In separate studies, we found that the gene for the proteoglycan fibromodulin (Fmod) controls a network of genes responsive to the action of brain trauma (EBiomed, 184(16) 2017). The action of Fmod (42-80 KDa) on the brain is poorly understood and rather known for affecting fibrillogenesis, cell adhesion, cytokine activity in the periphery. We found that deletion of Fmod gene mitigated the TBI-related increase in the pro-inflammatory marker toll like receptor 4 (TLR4), and attenuated a reduction in cell metabolic markers PGC1alpha and cytochrome oxidase II (COII), in the mouse hypothalamus after TBI. The latter suggests that Fmod deletion can protect against the cell metabolic crisis observed after TBI. In addition, given the regulatory role of the hypothalamus on peripheral metabolism, we sought to determine the effects of Fmod genetic deletion on the homeostasis of lipids in the liver on mice exposed to TBI. Results showed that the deletion of the Fmod gene protected against the action of brain trauma on key lipids and the levels of fatty acid synthase (FAS), a major lipogenic enzyme commonly involved in fatty acid processing. These results suggest a potential effect of Fmod on brain trauma outcome in brain and periphery.

SOX1 Is a Backup Gene for Brain Neurons and Glioma Stem Cell Protection and Proliferation.

Failed neuroprotection leads to the initiation of several diseases. SOX1 plays many roles in embryogenesis, oncogenesis, and male sex determination, and can promote glioma stem cell proliferation, invasion, and migration due to its high expression in glioblastoma cells. The functional versatility of the SOX1 gene in malignancy, epilepsy, and Parkinson's disease, as well as its adverse effects on dopaminergic neurons, makes it an interesting research focus. Hence, we collate the most important discoveries relating to the neuroprotective effects of SOX1 in brain cancer and propose hypothesis worthy of SOX1's role in the survival of senescent neuronal cells, its roles in fibroblast cell proliferation, and cell fat for neuroprotection, and the discharge of electrical impulses for homeostasis. Increase in electrical impulses transmitted by senescent cells affects the synthesis of neurotransmitters, which will modify the brain cell metabolism and microenvironment.

Successful intravenous thrombolysis for acute ischemic stroke caused by aortic dissection with severe hypofibrinogenemia: a case report and literature review

Background Intravenous thrombolysis (IVT) for acute brain infarctions caused by aortic dissection (AD) may lead to fatal outcomes; thus, it should be ruled out, especially if hypofibrinogenemia occurs after IVT. Successful management of AD-related acute brain infarction with hypofibrinogenemia after IVT has not been reported previously. Case report An 84-year-old woman developed sudden left limb weakness and aphasia for almost 4 h. Alteplase was administered intravenously immediately after cerebral hemorrhage was ruled out by emergent head computed tomography (CT). An anomaly suspected to be AD was detected during subsequent routine chest CT, which was confirmed by CT angiography to be a thoracoabdominal aortic dissecting aneurysm (DeBakey type I). Severe hypofibrinogenemia was also noted. After effective blood pressure control, intramuscular injection of vitamin K, and rehydration therapy, her brain cell metabolism improved, hemiplegia improved slightly, and hypofibrinogenemia recovered gradually. The patient’s cerebral hemorrhage did not progress, there was no chest pain or no aggravation of hemiplegia, and the fibrinogen level gradually returned to normal. The condition was stable during hospitalization. At 1.5 months after discharge, the patient showed minimal change in condition. Conclusion The symptoms of AD may be nonspecific and latent. IVT may be allowed to perform for some patients with AD related ischemical stroke, And IVT can improve the neural symptoms of AD-related ischemic stroke, but close monitoring is needed to avoid aneurysm rupture. Fibrinogen levels should also be monitored periodically after IVT for early detection of hypofibrinogenemia.

Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43266-283.

BackgroundGlioblastoma is the most aggressive primary brain tumour and has a very poor prognosis. Inhibition of c-Src activity in glioblastoma stem cells (GSCs, responsible for glioblastoma lethality) and primary glioblastoma cells by the peptide TAT-Cx43266–283 reduces tumorigenicity, and boosts survival in preclinical models. Because c-Src can modulate cell metabolism and several reports revealed poor clinical efficacy of various antitumoral drugs due to metabolic rewiring in cancer cells, here we explored the inhibition of advantageous GSC metabolic plasticity by the c-Src inhibitor TAT-Cx43266-283.MethodsMetabolic impairment induced by the c-Src inhibitor TAT-Cx43266-283 in vitro was assessed by fluorometry, western blotting, immunofluorescence, qPCR, enzyme activity assays, electron microscopy, Seahorse analysis, time-lapse imaging, siRNA, and MTT assays. Protein expression in tumours from a xenograft orthotopic glioblastoma mouse model was evaluated by immunofluorescence.FindingsTAT-Cx43266–283 decreased glucose uptake in human GSCs and reduced oxidative phosphorylation without a compensatory increase in glycolysis, with no effect on brain cell metabolism, including rat neurons, human and rat astrocytes, and human neural stem cells. TAT-Cx43266-283 impaired metabolic plasticity, reducing GSC growth and survival under different nutrient environments. Finally, GSCs intracranially implanted with TAT-Cx43266–283 showed decreased levels of important metabolic targets for cancer therapy, such as hexokinase-2 and GLUT-3.InterpretationThe reduced ability of TAT-Cx43266-283–treated GSCs to survive in metabolically challenging settings, such as those with restricted nutrient availability or the ever-changing in vivo environment, allows us to conclude that the advantageous metabolic plasticity of GSCs can be therapeutically exploited through the specific and cell-selective inhibition of c-Src by TAT-Cx43266-283.FundingSpanish Ministerio de Economía y Competitividad (FEDER BFU2015-70040-R and FEDER RTI2018-099873-B-I00), Fundación Ramón Areces. Fellowships from the Junta de Castilla y León, European Social Fund, Ministerio de Ciencia and Asociación Española Contra el Cáncer (AECC).

The impact of brain cell metabolism and extracellular matrix on magnesium degradation

Due to its degradability, magnesium holds potential for the application as a base material for local treatment systems. Particularly for the therapy of severe brain-related diseases, local approaches are advantageous. To confirm the suitability of magnesium as a material for neural implants, information on the interaction of brain cells with magnesium is essential. Initial steps of such an evaluation need to include not only cytocompatibility tests but also the analysis of the in vitro material degradation to predict in vivo material performance. Considering the sensitivity and functional importance of neural tissue, an in-depth understanding of the processes involved is of particular relevance. Here, we investigate the influence of four different brain cell types and fibroblasts on magnesium degradation in direct material contact. Our findings indicate cell type as well as cell density-dependent degradation behavior. Metabolic activity (lactate content) appears to be crucial for degradation promotion. Extracellular matrix composition, distribution, and matrix/cell ratios are analyzed to elucidate the cell-material interactions further.Statement of SignificanceThanks to their degradability, magnesium (Mg)-based materials could be promising biomaterials for local ion or even drug delivery strategies for the treatment of severe brain-related diseases. To confirm the suitability of Mg as a neural implant material, information on the interaction of brain cells with Mg is essential. Initial steps of such an evaluation need to include cytocompatibility tests and the analysis of the in vitro material degradation to predict in vivo material performance. The present study provides data on the influence of different brain cell types on Mg degradation in direct material contact. Our findings indicate cell type and cell density-dependent degradation behavior, and elucidate the role of cell metabolites and extracellular matrix molecules in the underlying degradation mechanisms.

Role of ECM in the Brain‐Gut Connection

We sought to determine the role of extracellular matrix (ECM) proteoglycans on regulating brain function and cell metabolism. In the first series of studies, we used dietary fructose to perturbate metabolism based on evidence that fructose is a major contributor to the epidemic of diabetes and obesity. Our transcriptomic studies (Meng et al, EBiomed, 157(7), 2016) showed that the gene for the proteoglycan biglycan (Bgn) occupies a central position in a network of genes receptive to the action of fructose in the hypothalamus (main brain center of metabolic control). We pursued studies further and exposed male biglycan knockout mice (Bgn0/−) to fructose for 7 weeks, and results showed that the Bgn0/− gene perturbation compensated for a decrement in learning and memory performance in mice exposed to fructose (Ying et al., BBADIS, 1864(12) 2018). Learning and memory performance was consistent with an attenuation of the action of fructose on hippocampal plasticity markers CREB and BDNF. Bgn siRNA treatment abolished the effects of fructose on CREB and BDNF levels, in conjunction with reducing a fructose‐related increase in Bgn protein. In addition, fructose consumption perturbed the systemic metabolism of glucose and lipids, that were also altered in the Bgn0/ mice. Transcriptomic profiling of hypothalamus, hippocampus, and liver supported the regulatory action of Bgn on key molecular pathways involved in metabolism, immune response, and neuronal plasticity. Overall results underscore the tissue‐specific role of the extracellular matrix in the regulation of metabolism and brain function, and support Bgn as a key modulator of the impact of fructose across body and brain. In separate studies, we found that the gene for the proteoglycan fibromodulin (Fmod) controls a network of genes responsive to the action of brain trauma (EBiomed, 184(16) 2017). The action of Fmod (42–80 KDa) on the brain is poorly understood and rather known for affecting fibrillogenesis, cell adhesion, cytokine activity in the periphery. We found that deletion of Fmod gene mitigated the TBI‐related increase in the pro‐inflammatory marker toll like receptor 4 (TLR4), and attenuated a reduction in cell metabolic markers PGC1alpha and cytochrome oxidase II (COII), in the mouse hypothalamus after TBI. The latter suggests that Fmod deletion can protect against the cell metabolic crisis observed after TBI. In addition, given the regulatory role of the hypothalamus on peripheral metabolism, we sought to determine the effects of Fmod genetic deletion on the homeostasis of lipids in the liver on mice exposed to TBI. Results showed that the deletion of the Fmod gene protected against the action of brain trauma on key lipids and the levels of fatty acid synthase (FAS), a major lipogenic enzyme commonly involved in fatty acid processing. These results suggest a potential effect of Fmod on brain trauma outcome in brain and periphery.Support or Funding InformationR01 NS50465, R01 DK104363

AMP-activated protein kinase (AMPK) regulates astrocyte oxidative metabolism by balancing TCA cycle dynamics.

AMP-activated protein kinase (AMPK) is an important energy sensor located in cells throughout the human body. From the periphery, AMPK is known to be a metabolic master switch controlling the use of energy fuels. The energy sensor is activated when the energy status of the cell is low, initiating energy-producing pathways and deactivating energy-consuming pathways. All brain cells are crucially dependent on energy production for survival, and the availability of energy substrates must be closely regulated. Intriguingly, the role of AMPK in the regulation of brain cell metabolism has been sparsely investigated, particularly in astrocytes. By investigating metabolism of 13 C-labeled energy substrates in acutely isolated hippocampal slices and cultured astrocytes, with subsequent mass spectrometry analysis, we here show that activation of AMPK increases glycolysis as well as the capacity of the TCA cycle, that is, anaplerosis, through the activity of pyruvate carboxylase (PC) in astrocytes. In addition, we demonstrate that AMPK activation leads to augmented astrocytic glutamate oxidation via pyruvate recycling (i.e., cataplerosis). This regulatory mechanism induced by AMPK activation is mediated via glutamate dehydrogenase (GDH) shown in a CNS-specific GDH knockout mouse. Collectively, these findings demonstrate that AMPK regulates TCA cycle dynamics in astrocytes via PC and GDH activity. AMPK functionality has been shown to be hampered in Alzheimer's and Parkinson's disease and our findings may therefore add to the toolbox for discovery of new metabolic drug targets.

Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle.

Creatine is pivotal in energy metabolism of muscle and brain cells, both in physiological and in pathological conditions. Additionally, creatine facilitates the differentiation of muscle and neuronal cells. Evidence of effectiveness of creatine supplementation in improving several clinical conditions is now substantial, and we review it in this paper. In hereditary diseases where its synthesis is impaired, creatine has a disease-modifying capacity, especially when started soon after birth. Strong evidence, including a Cochrane meta-analysis, shows that it improves muscular strength and general well-being in muscular dystrophies. Significant evidence exists also of its effectiveness in secondary prevention of statin myopathy and of treatment-resistant depression in women. Vegetarians and vegans do not consume any dietary creatine and must synthesize all they need, spending most of their methylation capacity. Nevertheless, they have a lower muscular concentration of creatine. Creatine supplementation has proved effective in increasing muscular and neuropsychological performance in vegetarians or vegans and should, therefore, be recommended especially in those of them who are athletes, heavy-duty laborers or who undergo intense mental effort. Convincing evidence also exists of creatine effectiveness in muscular atrophy and sarcopenia in the elderly, and in brain energy shortage (mental fatigue, sleep deprivation, environmental hypoxia as in mountain climbing, and advanced age). Furthermore, we review more randomized, placebo-controlled trials showing that creatine supplementation is safe up to 20 g/d, with a possible caveat only in people with kidney disease. We trust that the evidence we review will be translated into clinical practice and will spur more research on these subjects.

Modified Chitosan Membrane for Adsorption of GABA

Gamma-aminobutyric acid (GABA), the natural non-protein amino acid, is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone and improves cerebral blood flow and promoted the metabolism of brain cells. The drug delivery system is an efficiency way to delivery drug to the desired part of body in vivo movement, which can support its safety and control the dosage form. Nowadays, to make drug delivery through the mucosa is wildly studied, which would be regarded to have broad prospects. The chitosan can be prepared from natural biopolymer chitin and cast into membranes, whose sizes and shapes can be designed arbitrarily. It has been found that chitosan membrane stimulates the migration of inflammatory cells and promotes cellular organization. Modified chitosan membrane by glutaraldehyde can be changed the function group from amino group into aldehyde group. The oxidization changed the aldehyde group into carboxyl group, which finally can be used to absorb GABA which has the amino group. The different thickness and different modifying conditions of membrane were studied from the absorption test. The ninhydrin test was used to detect the GABA’s concentration which can monitor the absorption situation from the membrane. Finally, the optimum modifying condition was obtained and the tendency of absorption in different conditions A = A0 -Ar = Kb(C0 -Cr) was obtained.

Comment se libérer des souffrances mentales. Qu’est-ce que la résilience ?

Why and how do minds suffer? The prior and existing clinical classification and psychopathology cannot treat the suffering mind in an integrated way. In this article, resilience will be discussed at both invisible (mind) and visible (brain) level in relation to healing of the suffering mind. Our theory of neo organodynamism allows us to recognize the mental state as a spectrum ranging from a healthy to a pathological mental state. This theory seeks to eradicate prejudice against mental illness by highlighting the fact that anyone can become psychotic if they placed at the same environment and/or stress. How does the mind as a metaphysical entity can have an effect on the brain as a material entity? To answer this question, we have proposed the theory of psychiatric monistic parallelism. We wondered about the consciousness in its intrinsic definition through approach to life as a fundamental particle. The use of the weak measurement in quantum mechanics that can obtain the information of a mental state without disturbing its state allows us to reach their individual virtuality. The resilience is considered as the power of restoration of the mind-body complex and the spontaneous power of remission. In other words, considering the resilience as the visible level (the brain) and the invisible level (mind) makes possible to gain the key for cure from a pathological mental state. For this, we must understand first what the mental disorder is. The psychosis is the synaptic disorder as the visible result, but its true origin is in the mind. The mind cannot get sick. We do not know all the elements that constitute the mind as itself. The environment influences the neural network of the brain by sensory perceptions (quantum potential), then the psychotic symptoms are observed. The environment determines the dynamism of the neural network. Although the mind seems to be dominated by uncertainty, the influence of the environment can act and change the mental state. Thus, the mental state is constantly changing depending on the surrounding environment. Therefore, we can see that all mental disorders are spectrum of the mental state. According to our theory of psychiatric monistic parallelism, the event changes the magnetic field strength and makes appear an individual virtuality. The mind is thus transformed into a function of the modified strength in the magnetic field, it is called “Intensité”. The “Intensité” can act directly on brain cells by changing the potential of the neuronal cell membrane. Thereby, the “Intensité” influences the metabolism of brain cells. The mental transformation that is caused by the change in the environment may be occurred as a result of a changed state of the potential of the network of neural circuit and of a modification of the strength of an individual magnetic field (the “Intensité”). The mind (the invisible entity) and brain (the visible entity) can be considered as a magnetic material, and mutually interact each other through this magnetic effect. The “Intensité” moves on the spectrum of psychic state. Therefore, the change of the mental state is the change of the “Intensité”. The “Intensité” that undergoes the influence of the mental state varies depending on the degree of disorder of the meta-noesis. The mental state varies between a healthy state and a psychopathological state, following the organic degeneration caused by various influences such as stress. The displacement of the “Intensité” to the upstream in the spectrum of mental state is called resilience, or spontaneous remission. And its downstream displacement is considered the worsening of the mental state. The “Intensité” itself can become either the aggravating factor of the mental state or the engine of the resilience. At the visible level of the resilience, the basis of mental transformation is mainly the remodeling of the GABAergic neural network. In other words, before the reorganization of the pathogen synapse fixed by neuronal accessory pathways formed by stress stimuli, it is needed for the resilience that restoring original neuronal conduction of the main neural network must be primarily carried out. In this meaning, we must focus on the rehabilitation and the repetition of learning and activities for the visible level of resilience. This is the mechanism of resilience or spontaneous remission in the visible and invisible level.

Clinical effect of electroencephalographic biofeedback therapy in treatment of memory disorders in patients with acute severe toxic encephalopathy

Objective: To investigate the clinical effect and safety of electroencephalographic biofeedback therapy in improving memory disorders in patientsin the recovery stage of acute severe toxic encephalopathy. Methods: A total of 52 patients in the recovery stage of acute severe toxic encephalopathy who were hospitalized in our hospital from March 2013 to December 2016 were enrolled and randomly divided into observation group with 27 patients and control group with 25 patients. Both groups were given the drugs to promote the metabolism of brain cells,and the patients in the observation group were given electroencephalographic biofeedback therapy in addition. The Chinese revised version of Wechsler Memory Scale Type A was used to measure memory ability before and after each course of treatment. The treatment outcome was evaluated for both groups. Results: There were no significant differences in the scores of long-term memory,short-term memory, immediate memory, and memory quotient between the two groups before treatment(P>0.05).After the first course of treatment ended, the observation group had significant increases in the scores of forward task,backward task,association,and memory quotient(P<0.05); compared with the control group, the observation group had a significant reduction in the score of backward task(P<0.05).After the second course of treatmentended, the observation group had significant increases in the scores offorward task,backward task,memorization of pictures,reproduction,association,comprehension,and memory quotient,and the control group had significant increases in the scores of reproduction,association,comprehension,and memory quotient(P<0.05); compared with the control group, the observation group had significant increases in the scores of forward task,backward task,memorization of pictures, reproduction, association, comprehension, and memory quotient(P<0.05).Two patients experiencedchest distress, palpitation, and dysphoria during treatment, which did not affect the treatment. Conclusion: Electroencephalographic biofeedback therapy has a certain effect in the treatment of memory disorders in patients with acute severe toxic encephalopathy.

Abnormalities of signal transduction networks in chronic schizophrenia

Schizophrenia is a serious neuropsychiatric disorder characterized by disruptions of brain cell metabolism, microstructure, and neurotransmission. All of these processes require coordination of multiple kinase-mediated signaling events. We hypothesize that imbalances in kinase activity propagate through an interconnected network of intracellular signaling with potential to simultaneously contribute to many or all of the observed deficits in schizophrenia. We established a workflow distinguishing schizophrenia-altered kinases in anterior cingulate cortex using a previously published kinome array data set. We compared schizophrenia-altered kinases to haloperidol-altered kinases, and identified systems, functions, and regulators predicted using pathway analyses. We used kinase inhibitors with the kinome array to test hypotheses about imbalance in signaling and conducted preliminary studies of kinase proteins, phosphoproteins, and activity for kinases of interest. We investigated schizophrenia-associated single nucleotide polymorphisms in one of these kinases, AKT, for genotype-dependent changes in AKT protein or activity. Kinome analyses identified new kinases as well as some previously implicated in schizophrenia. These results were not explained by chronic antipsychotic treatment. Kinases identified in our analyses aligned with cytoskeletal arrangement and molecular trafficking. Of the kinases we investigated further, AKT and (unexpectedly) JNK, showed the most dysregulation in the anterior cingulate cortex of schizophrenia subjects. Changes in kinase activity did not correspond to protein or phosphoprotein levels. We also show that AKT single nucleotide polymorphism rs1130214, previously associated with schizophrenia, influenced enzyme activity but not protein or phosphoprotein levels. Our data indicate subtle changes in kinase activity and regulation across an interlinked kinase network, suggesting signaling imbalances underlie the core symptoms of schizophrenia.

Endogenous Two-Photon Excited Fluorescence Imaging Characterizes Neuron and Astrocyte Metabolic Responses to Manganese Toxicity

As neurodegenerative conditions are increasingly linked to mitochondrial dysfunction, methods for studying brain cell metabolism at high spatial resolution are needed to elucidate neurodegeneration mechanisms. Two-photon excited fluorescence (TPEF) imaging is a non-destructive, high-resolution technique for studying cell metabolism via endogenous fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat astrocyte and neuronal cultures under normal growth conditions and in response to manganese (Mn) treatment. Histograms of pixel-wise optical redox ratio, defined as FAD/(FAD + NAD(P)H), revealed three distinct redox distributions and significant differences in their relative weights between astrocytes and neurons. When treated with Mn, both cell types exhibited redox ratio shifts consistent with increased oxidative stress. However, the manner in which the redox distributions was affected was distinct for the two cell types. Furthermore, NAD(P)H fluorescence lifetime imaging revealed an increase in bound NAD(P)H fraction upon Mn treatment for neurons, consistent with enhanced apoptosis. Astrocytes showed a decrease in bound fraction, possibly due to a shift towards glycolytic metabolism in response to impaired respiration. These results exhibit TPEF’s utility for characterizing detailed metabolic changes of different brain cell types in response to neurotoxins.