Brain Cell Function Research Articles

Multi-target action of β-alanine protects cerebellar tissue from ischemic damage

Brain ischemic stroke is among the leading causes of death and long-term disability. New treatments that alleviate brain cell damage until blood supply is restored are urgently required. The emerging focus of anti-stroke strategies has been on blood-brain-barrier permeable drugs that exhibit multiple sites of action. Here, we combine single-cell electrophysiology with live-cell imaging to find that β-Alanine (β-Ala) protects key physiological functions of brain cells that are exposed to acute stroke-mimicking conditions in ex vivo brain preparations. β-Ala exerts its neuroprotective action through several distinct pharmacological mechanisms, none of which alone could reproduce the neuroprotective effect. Since β-Ala crosses the blood-brain barrier and is part of a normal human diet, we suggest that it has a strong potential for acute stroke treatment and facilitation of recovery.

Rationalizing the Use of Polyphenol Nano-formulations in the Therapy of Neurodegenerative Diseases.

Neurodegenerative diseases are a heterogeneous group of disorders among aging populations worldwide characterized by the progressive degeneration of the structure and function of brain cells and the nervous system. Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases (NDs). Classic pathological features of AD are the accumulation of the amyloid betaprotein and aggregates of hyperphosphorylated tau protein around the brain cells. Dopaminergic neuronal death in the midbrain and accumulation of α- synuclein in the neurons are the hallmark of Parkinson's disease. The pathogenesis is multifactorial, and both neurodegenerative disorders have complex etiology. Oxidative stress closely linked with mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation, is anticipated to trigger neuronal death. Ample evidence has implicated that oxidative stress and inflammation contribute to the pathology of neurodegeneration in AD and PD. Currently, acetylcholinesterase inhibitors are the main treatment option for AD, while L-DOPA is the gold standard therapy for PD. Along with the main therapy, many endogenous antioxidants, like vitamin E, selenium, etc., are also given to the patients to combat oxidative stress. Current treatment for these NDs is limited due to the blood-brain barrier (BBB) that hinders drug targeting towards neurons. In this review, we emphasize adjunct treatment with anti-inflammatory agents that act at the site of the disease and can halt the disease progression by attenuating the effect of ROS triggering neuro-inflammatory response. Polyphenols, either as purified compounds or extracts from various natural plant sources, have been well studied and documented for anti-inflammatory effects, but their use for ND is limited due to their physicochemical attributes. Nanoparticle-mediated drug delivery system exhibits immense potential to overcome these hurdles in drug delivery to the CNS, enabling nanoparticle-based therapies to directly target the inflammation and release bioactive compounds with anti-inflammatory properties to the site of action.

Rainer Waser – A Pioneer of Fundamentals of Resistive Switching Memories

Rainer Waser – A Pioneer of Fundamentals of Resistive Switching Memories

Ahead of the Curve: The Arc Institute Aims to Reshape the Biomedical Research Landscape

Ahead of the Curve: The Arc Institute Aims to Reshape the Biomedical Research Landscape

Multiscale Mechanobiology in Brain Physiology and Diseases.

Increasing evidence suggests that mechanics play a critical role in regulating brain function at different scales. Downstream integration of mechanical inputs into biochemical signals and genomic pathways causes observable and measurable effects on brain cell fate and can also lead to important pathological consequences. Despite recent advances, the mechanical forces that influence neuronal processes remain largely unexplored, and how endogenous mechanical forces are detected and transduced by brain cells into biochemical and genetic programs have received less attention. In this review, we described the composition of brain tissues and their pronounced microstructural heterogeneity. We discuss the individual role of neuronal and glial cell mechanics in brain homeostasis and diseases. We highlight how changes in the composition and mechanical properties of the extracellular matrix can modulate brain cell functions and describe key mechanisms of the mechanosensing process. We then consider the contribution of mechanobiology in the emergence of brain diseases by providing a critical review on traumatic brain injury, neurodegenerative diseases, and neuroblastoma. We show that a better understanding of the mechanobiology of brain tissues will require to manipulate the physico-chemical parameters of the cell microenvironment, and to develop three-dimensional models that can recapitulate the complexity and spatial diversity of brain tissues in a reproducible and predictable manner. Collectively, these emerging insights shed new light on the importance of mechanobiology and its implication in brain and nerve diseases.

THE UTILIZATION OF RED MEAT WASTE IN THE MAKING OF CRACKERS

Red Tuna Fish waste contains vitamin B6 which functions to increase hemoglobin production, maintain brain cell function, and help the body produce serotonin and norepineprine hormones. The formulation of the problem in this study is what is the right composition for making tuna red meat crackers. How is the community's acceptance of the quality of the addition of tuna red meat crackers. The research objectives were to determine the exact composition of tuna red meat crackers and to determine the public acceptance of the quality of crackers with the addition of tuna red meat waste based on color, taste, aroma and texture.
 This research uses analytic observational research where the research is conducted by analyzing acceptance. The population used was 352 people in Bilato Village, Bilato District and a sample of 176 respondents. Data collection techniques using hedonic questionnaires with data analysis techniques using qualitative descriptive analysis.
 The results showed that the crackers preferred by the panelists were 100 gr and 200 gr with very like criteria but the most preferred by the panelists were 100 gr crackers with very like criteria, 50 gr crackers were less preferred by the panelists with moderate criteria. Suggestions from research for campus institutions as references and information for further research, for students to further modify the food material for tuna red meat waste so that it can be used as the latest research material and see the RDA contained in fish waste red meattuna

Post-treatment with apocynin at a lower dose regulates the UPR branch of eIF2α and XBP-1 pathways after stroke

Stroke leads to disturbance in the physiology of the ER (Endoplasmic Reticulum) that triggers UPR (Unfolded Protein Response) pathways aimed to compensate neuronal cell damage. However, sustained UPR causes stressful conditions in the ER lumen forming abnormal protein aggregates. Stroke-induced oxidative stress also amalgamates with UPR to safeguard and ensure the proper functioning of brain cells. Thus we tested the effect of apocynin (a potent antioxidant) post-treatment in experimental stroke on the outcome of ER stress and UPR branch pathways. We administered a low dose of apocynin at 1 mg/kg (intraperitoneal) to adult Sprague-Dawley rats subjected to Middle Cerebral Artery Occlusion (MCAO) for two-time points. The first dose immediately after re-establishing the blood flow and another at 6 h of reperfusion. Apocynin post-treatment significantly reduced ROS (Reactive Oxygen Species) generation at an early reperfusion time point of 4 h. It preserved neuronal morphology, dendritic spine density, reduced protein aggregation, and brain damage after 24 h of reperfusion. Apocynin post-treatment regulates the two UPR branch pathways in our experimental paradigm. 1) Down-regulation of eIF2α (Eukaryotic Initiation Factor 2α) phosphorylation, and CHOP (C/EBP homologous protein) 2) by reducing the XBP-1 (X-Box binding Protein-1) mRNA splicing downstream to PERK (Protein Kinase RNA-Like ER Kinase) and IRE1α (Inositol Requiring Enzyme 1alpha) UPR pathways, respectively. Bioinformatics prediction showed that apocynin has binding sites for PERK (Protein Kinase RNA-Like ER Kinase) and IRE1α proteins. The amino acid residues interacting with apocynin were Cys891 and Gln889 (for PERK), and the amino acids Ser726, Arg722, and Ala719 (for IRE1α) lying within their activation loop. Overall, these studies indicate that apocynin post-treatment might regulate ER stress/UPR pathways and minimize stroke brain damage, thus having implications for developing newer strategies for stroke treatment.

Efektifitas Pijat Bayi Terhadap Penambahan Berat Badan Bayi Di Klinik Kusuma Husada Bayat

Baby massage is one of the recommended stimulations to stimulate the development of brain cell function. Baby massage has a hungry effect on babies due to an increase in vagus nerve muscle tone to facilitate the release of food absorption hormones and increase levels of gastrin and insulin enzymes so that babies who are massaged experience weight gain more rapidly. The purpose of this study was to determine the effectiveness of infant massage on infant weight gain at the Kusuma Husada Bayat Clinic. The design of this research was descriptive correlation with a retrospective approach. The research sample was all babies who did baby massage from February to March 2021 at the Kusuma Husada Bayat Clinic. A total of 32 babies. The sampling technique used total sampling. The instrument used was an observation sheet. Data analysis using chi square test. The results of the study of babies who did routine baby massage had a weight increase of 21 with a percentage of 65.6% while babies who did not routinely do baby massage did not increase their weight by 9 babies with a percentage of 28.1% and the results of bivariate analysis obtained p value 0.000 ( p < 0.05). The conclusion of this study is that Baby Massages effective in increasing infant weight at the Kusuma Husada Bayat Clinic, Klaten. It is recommended that mothers massage their babies more regularly because of the many benefits and good effects for the health and growth of babies

Neuroprotective agents effective against radiation damage of central nervous system.

Ionizing radiation caused by medical treatments, nuclear events or even space flights can irreversibly damage structure and function of brain cells. That can result in serious brain damage, with memory and behavior disorders, or even fatal oncologic or neurodegenerative illnesses. Currently used treatments and drugs are mostly targeting biochemical processes of cell apoptosis, radiation toxicity, neuroinflammation, and conditions such as cognitive-behavioral disturbances or others that result from the radiation insult. With most drugs, the side effects and potential toxicity are also to be considered. Therefore, many agents have not been approved for clinical use yet. In this review, we focus on the latest and most effective agents that have been used in animal and also in the human research, and clinical treatments. They could have the potential therapeutical use in cases of radiation damage of central nervous system, and also in prevention considering their radioprotecting effect of nervous tissue.

Common genetic signatures of Alzheimer's disease in Down Syndrome.

Background: People with Down Syndrome (DS) are born with an extra copy of Chromosome (Chr) 21 and many of these individuals develop Alzheimer's Disease (AD) when they age. This is due at least in part to the extra copy of the APP gene located on Chr 21. By 40 years, most people with DS have amyloid plaques which disrupt brain cell function and increase their risk for AD. About half of the people with DS develop AD and the associated dementia around 50 to 60 years of age, which is about the age at which the hereditary form of AD, early onset AD, manifests. In the absence of Chr 21 trisomy, duplication of APP alone is a cause of early onset Alzheimer's disease, making it likely that having three copies of APP is important in the development of AD and in DS. Methods: We investigate the relationship between AD and DS through integrative analysis of genesets derived from a MeSH query of AD and DS associated beta amyloid peptides, Chr 21, GWAS identified AD risk factor genes, and differentially expressed genes in individuals with DS. Results: Unique and shared aspects of each geneset were evaluated based on functional enrichment analysis, transcription factor profile and network interactions. Genes that may be important to both disorders in the context of direct association with APP processing, Tau post translational modification and network connectivity are ACSM1, APBA2, APLP1, BACE2, BCL2L, COL18A1, DYRK1A, IK, KLK6, METTL2B, MTOR, NFE2L2, NFKB1, PRSS1, QTRT1, RCAN1, RUNX1, SAP18 SOD1, SYNJ1, S100B. Conclusions: Our findings confirm that oxidative stress, apoptosis, inflammation and immune system processes likely contribute to the pathogenesis of AD and DS which is consistent with other published reports.

Common genetic signatures of Alzheimer’s disease in Down Syndrome

Background: People with Down Syndrome (DS) are born with an extra copy of Chromosome (Chr) 21 and many of these individuals develop Alzheimer’s Disease (AD) when they age. This is due at least in part to the extra copy of the APP gene located on Chr 21. By 40 years, most people with DS have amyloid plaques which disrupt brain cell function and increase their risk for AD. About half of the people with DS develop AD and the associated dementia around 50 to 60 years of age, which is about the age at which the hereditary form of AD, early onset AD, manifests. In the absence of Chr 21 trisomy, duplication of APP alone is a cause of early onset Alzheimer’s disease, making it likely that having three copies of APP is important in the development of AD and in DS. Methods: We investigate the relationship between AD and DS through integrative analysis of genesets derived from a MeSH query of AD and DS associated beta amyloid peptides, Chr 21, GWAS identified AD risk factor genes, and differentially expressed genes in individuals with DS. Results: Unique and shared aspects of each geneset were evaluated based on functional enrichment analysis, transcription factor profile and network interactions. Genes that may be important to both disorders in the context of direct association with APP processing, Tau post translational modification and network connectivity are ACSM1, APBA2, APLP1, BACE2, BCL2L, COL18A1, DYRK1A, IK, KLK6, METTL2B, MTOR, NFE2L2, NFKB1, PRSS1, QTRT1, RCAN1, RUNX1, SAP18 SOD1, SYNJ1, S100B. Conclusions: Our findings confirm that oxidative stress, apoptosis, inflammation and immune system processes likely contribute to the pathogenesis of AD and DS which is consistent with other published reports.

Brain-Protective Mechanisms of Transcription Factor NRF2: Toward a Common Strategy for Neurodegenerative Diseases.

Neurodegenerative diseases are characterized by the loss of homeostatic functions that control redox and energy metabolism, neuroinflammation, and proteostasis. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is a master controller of these functions, and its overall activity is compromised during aging and in these diseases. However, NRF2 can be activated pharmacologically and is now being considered a common therapeutic target. Many gaps still exist in our knowledge of the specific role that NRF2 plays in specialized brain cell functions or how these cells respond to the hallmarks of these diseases. This review discusses the relevance of NRF2 to several hallmark features of neurodegenerative diseases and the current status of pharmacological activators that might pass through the blood-brain barrier and provide a disease-modifying effect.

From microbial membrane proteins to the mysteries of emotion

On the occasion of the 2021 Lasker Basic Medical Research Award to Karl Deisseroth, Peter Hegemann, and Dieter Oesterhelt (for "the discovery of light-sensitive microbial proteins that can activate or deactivate individual brain cells-leading to the development of optogenetics and revolutionizing neuroscience"), Deisseroth reflects on this international collaboration, his basic mechanistic and structural discoveries regarding microbial channels that transduce photons into ion current, the causal exploration of brain cell function, and the pressing mysteries of psychiatry.

A Transcriptome Community-and-Module Approach of the Human Mesoconnectome.

Graph analysis allows exploring transcriptome compartments such as communities and modules for brain mesostructures. In this work, we proposed a bottom-up model of a gene regulatory network to brain-wise connectome workflow. We estimated the gene communities across all brain regions from the Allen Brain Atlas transcriptome database. We selected the communities method to yield the highest number of functional mesostructures in the network hierarchy organization, which allowed us to identify specific brain cell functions (e.g., neuroplasticity, axonogenesis and dendritogenesis communities). With these communities, we built brain-wise region modules that represent the connectome. Our findings match with previously described anatomical and functional brain circuits, such the default mode network and the default visual network, supporting the notion that the brain dynamics that carry out low- and higher-order functions originate from the modular composition of a GRN complex network

Electrochemical Investigations of Tau Protein Biochemistry

Proteins play important biological functions and are commonly associated with a variety of diseases. One such protein is tau protein, which maintains brain cell function and is linked to neurodegeneration. The complex tau protein biochemistry is composed of the post-translational modifications, interactions with binding partners and aggregation, among other pathways. To investigate the complex biochemistry of tau protein, we utilized electrochemical methods (cyclic voltammetry and electrochemical impedance spectroscopy. We demonstrated detection of protein-protein interactions (1), protein-ligand interactions (2), enzymatic catalysis and enzyme inhibition (3). For this purpose, tau protein film on Au surface was fabricated and characterized. Tau-Au films were used to probe interactions with heparin, ferritin, transferrin, antibodies, and protein kinases. Our data indicate that tau-Au films are functional surfaces which allow for monitoring biomolecular interactions, and enzymatic transformations.References(1) a) Carlin, N., Martic-Milne (2018) J. Electrochem. Soc. 165: G3018-G3025. b) Jahshan, A., Esteves, J.O., Martic-Milne (2016) J. Inorg. Biochem. 162: 127-134.(2) Trzeciakiewicz, H., Esteves, J. O.V., Carlin, N., Martic, S. (2015) Electrochim. Acta 162: 24-30.(3) Esteves, J.O.V., Martic-Milne, S. (2016) Anal. Biochem. 496: 55-62.

Патофізіологічні механізми розвитку епілепсії та особливості епілептогенезу в незрілому мозку

The article is devoted to the urgent problem of neonatology and pediatric neurology — seizures in newborns and young children. The work analyzes the scientific literature on the pathogenetic mechanisms of the development of the epileptic process, which is based on the anatomical and physiological mechanisms of the functioning of brain cells, in particular, in newborns and young children. New pathophysiological data on the increased excitability of the developing brain are described. It has been shown that the implementation of the mechanism of increased excitability of the fetal brain may be due to the peculiarities of the functioning of NMDA, AMPA, kainate receptors, and the peculiarities of the localization of ion channels in different brain structures. The paradoxical (exciting, depolarizing) role of gamma-aminobutyric acid, which is due to the peculiarities of the activation of chlorine co-transporters, is emphasized. The features of the epileptic process in newborns and young children have been determined. The reasons for the development of seizures in newborns are emphasized. The classification and clinical phenotypes of neonatal seizures are considered. It is emphasized that the convulsions in newborns rarely have a deployed clinical picture and are often represented by abortive or focal seizures, which is associated with the ontogenetic features of the fetal brain, namely: incomplete by the time of the birth of a cortical-neural organization, synaptogenesis and myelination of its structures, insufficiency of the development of commulectral intermetrous bonds , uneven representation in the cortex of ion channels with a relatively well-formed limbico-reticular system and its bond with a brain barrel. It was noted that despite various clinical manifestations, the newborn has four main types of seizures: subtitle (erased, abortive, fragmentary), tonic, clonic and myocloniс. No conflict of interest was declared by the authors. Key words: newborn, brain, pathophysiology, seizures, epilepsy, review.

The effects of morphine, methadone, and fentanyl on mitochondria: A live cell imaging study

The important role of mitochondria in maintaining normal brain cell function has been demonstrated in several neurodegenerative diseases where mitochondrial dysfunction is a prominent feature. Accumulating evidence indicates that opioids may induce neuronal cell death and inhibit neurogenesis, two factors that are dependent on normal mitochondrial function. The aim of the present study was to examine the effects of morphine, methadone, and fentanyl on MitoTracker-stained mitochondria. Cells from the neuroblastoma/glioma hybrid cell-line NG108−15 were seeded on 96-well cell culture plates and treated with MitoTracker for 30 min prior to opioid treatment. Morphine, methadone, and fentanyl were added at various concentrations and images of mitochondria were acquired every 30 min for four hours using a high-content imaging device. The parameters total mitochondrial area, mitochondrial network, as well as the number and mean area of mitochondrial objects were analyzed using automated image analysis. Methadone and fentanyl, but not morphine, decreased the mitochondrial network, the number of mitochondrial objects, and increased the mean area of mitochondrial objects. Both methadone and fentanyl altered mitochondrial morphology with no effects seen from morphine treatment. These data suggest that methadone and fentanyl impact mitochondrial morphology negatively, which may be associated with neuronal cell death.

Advanced imaging and labelling methods to decipher brain cell organization and function.

The brain is arguably the most complex organ. The branched and extended morphology of nerve cells, their subcellular complexity, the multiplicity of brain cell types as well as their intricate connectivity and the scattering properties of brain tissue present formidable challenges to the understanding of brain function. Neuroscientists have often been at the forefront of technological and methodological developments to overcome these hurdles to visualize, quantify and modify cell and network properties. Over the last few decades, the development of advanced imaging methods has revolutionized our approach to explore the brain. Super-resolution microscopy and tissue imaging approaches have recently exploded. These instrumentation-based innovations have occurred in parallel with the development of new molecular approaches to label protein targets, to evolve new biosensors and to target them to appropriate cell types or subcellular compartments. We review the latest developments for labelling and functionalizing proteins with small localization and functionalized reporters. We present how these molecular tools are combined with the development of a wide variety of imaging methods that break either the diffraction barrier or the tissue penetration depth limits. We put these developments in perspective to emphasize how they will enable step changes in our understanding of the brain.

Structural and Biochemical Characterization of EFhd1/Swiprosin-2, an Actin-Binding Protein in Mitochondria.

Ca2+ regulates several cellular functions, including signaling events, energy production, and cell survival. These cellular processes are mediated by Ca2+-binding proteins, such as EF-hand superfamily proteins. Among the EF-hand superfamily proteins, allograft inflammatory factor-1 (AIF-1) and swiprosin-1/EF-hand domain-containing protein 2 (EFhd2) are cytosolic actin-binding proteins. AIF-1 modulates the cytoskeleton and increases the migration of immune cells. EFhd2 is also a cytoskeletal protein implicated in immune cell activation and brain cell functions. EFhd1, a mitochondrial fraternal twin of EFhd2, mediates neuronal and pro-/pre-B cell differentiation and mitoflash activation. Although EFhd1 is important for maintaining mitochondrial morphology and energy synthesis, its mechanism of action remains unclear. Here, we report the crystal structure of the EFhd1 core domain comprising a C-terminus of a proline-rich region, two EF-hand domains, and a ligand mimic helix. Structural comparisons of EFhd1, EFhd2, and AIF-1 revealed similarities in their overall structures. In the structure of the EFhd1 core domain, two Zn2+ ions were observed at the interface of the crystal contact, suggesting the possibility of Zn2+-mediated multimerization. In addition, we found that EFhd1 has Ca2+-independent β-actin-binding and Ca2+-dependent β-actin-bundling activities. These findings suggest that EFhd1, an actin-binding and -bundling protein in the mitochondria, may contribute to the Ca2+-dependent regulation of mitochondrial morphology and energy synthesis.

Molecular mechanisms of zika virus pathogenesis: An update.

Zika virus (ZIKV), member of the family Flaviviridae belonging to genus Flavivirus, is an arthropod-borne virus. The ZIKV is known to cause severe congenital birth defects in neonates. Due to a large number of worldwide outbreaks and associated neurological complications with ZIKV, a public health emergency was declared by the World Health Organization on February 1, 2016. The virus exhibits neurotropism and has a specific propensity towards neural precursor cells of the developing brain. In utero ZIKV infection causes massive cell death in the developing brain resulting in various motor and cognitive disabilities in newborns. The virus modulates cell machinery at several levels to replicate itself and inhibits toll like receptors-3 signalling, deregulates microRNA circuitry and induces a chronic inflammatory response in affected cells. Several significant advances have been made to understand the mechanisms of neuropathogenesis, its prevention and treatment. The current review provides an update on cellular and molecular mechanisms of ZIKV-induced alterations in the function of various brain cells.