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Spinal cord injury (SCI) results in a cascade of primary and secondary damage, with apoptosis being a prominent cause of neuronal cell death. The X-linked inhibitor of apoptosis (XIAP) plays a critical role in inhibiting apoptosis, but its expression is reduced following SCI, contributing to increased neuronal vulnerability. This study investigates the regulatory role of miR-199a-5p on XIAP expression in the context of SCI. Using bioinformatic tools, luciferase reporter assays, and in vitro and in vivo models of SCI, we identified miR-199a-5p as a post-transcriptional regulator of XIAP. Overexpression of miR-199a-5p significantly reduced XIAP protein levels, although no changes were observed at the mRNA level, suggesting translational repression. In vivo, miR-199a-5p expression was upregulated at 3 and 7 days post-injury, while XIAP expression inversely decreased in both neurons and oligodendrocytes, being particularly significant in the latter at 7 dpi. These findings suggest that miR-199a-5p contributes to the downregulation of XIAP and may exacerbate neuronal apoptosis after SCI. Targeting miR-199a-5p could offer a potential therapeutic strategy to modulate XIAP levels and reduce apoptotic cell death in SCI. [ABSTRACT FROM AUTHOR]

Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1s activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons. Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development.

Macrobrachium rosenbergii is one of the most popular species in aquaculture. However, the M. rosenbergii farming industry has been facing an ongoing iron prawn syndrome (IPS) crisis since 2010, resulting in substantial economic losses to the farming industry. Infectious precocity virus (IPV) is a novel virus of Flaviviridae found in recent years that can cause sexual precocity and associated slow growth in healthy M. rosenbergii. It is believed to have a specific correlation with IPS. There are very few cell lines of crustaceans that can be used for studying the response of cells to pathogens. Even though the primary culture technology of blood and muscle cells in M. rosenbergii has gradually matured, there have been few studies on the primary culture of neural cells. Quantitative results of different tissues of IPV-positive M. rosenbergii have indicated that nerve-rich tissues, such as eyestalk, brain, and thoracic ganglion tissues, have a higher viral load, which explains why IPV has neurotropic tissue characteristics. To provide an in vitro cell platform for studying the virus-host interactions of IPV, a simple, stable, and feasible primary culture method was established for the nervous tissue primary cells of M. rosenbergii.In this study, healthy prawns with a body length of about 10–12 cm, healthy appendages, and vitality were selected for the experiments. The body surface of M. rosenbergii was first disinfected with 75% alcohol. On the clean bench, the nervous tissues, including the brain, X organ-sinus gland complex from the eyestalk, thoracic ganglion, and abdominal ganglion tissues, were isolated and washed in PBS buffer containing 100 U/mL penicillin and streptomycin, 100 U/mL amphotericin, and 80 U/mL gentamicin, 2–3 times. The tissues were then placed in 5 mL of 0.5% papain solution. After digestion at 25 ℃ for 5 min, 1× L-15 medium containing 15% FBS, 140 mmol/L D-glucose, and antibiotics (100 U/mL penicillin and streptomycin, 100 U/mL amphotericin, and 80 U/mL gentamicin) were added to terminate digestion. Next, the cells were seeded onto a 24-well plate and allowed to settle in darkness at 25 ℃ for 45 min. After adhesion, cells were transferred to a cell incubator and cultured in the dark at 28 ℃. The nervous tissues' primary cells at different time points were observed under an inverted microscope, and the morphological changes were recorded through imaging. The compound eye tissue of IPV-positive M. rosenbergii was placed in SM buffer, and the IPV mixture was obtained after multiple rounds of crushing and centrifugation. The brain tissue primary cells with large quantities and better culture effects were selected for the IPV challenge after cultured in vitro for 5 days. The virus crude extract was filtered through a 0.22 μm filter membrane and mixed according to the volume ratio of virus crude extract to serum-free medium = 1∶9. For the experimental group, 2 mL of the mixed solution was added to each well, while the control group received 2 mL of serum-free medium per well. Samples were taken at 0, 6, 12, 24, 48, and 96 h after virus infection. RT-qPCR was used to detect the IPV load.The results showed that the cultured primary cells grew well in a 1× L-15 medium containing glutamine and serum. According to the morphology of the cells, number of axons, and other characteristics, brain tissue primary cells, primary cells from the eyestalk X organ-sinus gland complex, and thoracic ganglion tissue primary cells were divided into four types: neurosecretory cells, pseudounipolar neural cell-like, bipolar neural cell-like, and multipolar neural cell-like, respectively. In comparison, only round neural cells and bipolar-like neural cells were found in the primary cell culture of the abdominal ganglion tissue under in vitro culture. The brain tissue primary cells and X organ-sinus gland complex cells survived for 15 days, while the thoracic ganglion and abdominal ganglion tissue primary cells survived for 9 days after being cultured in vitro. After IPV infected the brain tissue primary cells, the viral load of IPV was 15.30 copies/μg RNA at 6 h post-infection (hpi) and 35.59 copies/μg RNA at 12 hpi. IPV was not detected in IPV-infected brain tissue primary cells at 24 hpi and 48 hpi. Then, IPV viral load was detected at 96 hpi, reaching 104 copies/μg RNA.In conclusion, this study successfully established a simple and convenient primary culture technology for cells from M. rosenbergii neural tissues, providing preliminary data and a platform for neuroendocrine and virus-host interactions research. An in vitro infection model of IPV was also initially established in this study. Before establishing the shrimp cell line, the cells could be used to study the mechanism of viral infection, replication, and transcription, providing primary data and a platform for studying the norovirus and neuroendocrine factors of M. rosenbergii. They could also provide critical experimental materials for further research into infection mechanisms and the development of virus and disease prevention technologies.

Simple Summary: Brain aging in mammals is characterized by morphological and functional changes in neural cells. This process, although physiological, leads to progressive cerebral tissue volume loss and functional decline, including memory loss motor neuron deficits and behavioral disorders. It is generally accepted that aging is associated with a shift in the proportion between the functional cell (neuron) and support cells (astrocytes) in favor of the latter, which also appear different from those of healthy and young brain tissue. Also, dysfunctional autophagy contributes to altering brain homeostasis. This review summarizes and updates the most recent knowledge about brain aging through a comparative approach, where similarities and differences in some mammalian species are considered. Brain aging in mammals is characterized by morphological and functional changes in neural cells. Macroscopically, this process, leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron deficits, as well as behavioral disorders. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro, including cell cycle arrest, increased lysosomal activity, telomere shortening, oxidative stress, and DNA damage. The most common markers for senescence identification were identified in (i) proteins implicated in cell cycle arrest, such as p16, p21, and p53, (ii) increased lysosomal mass, and (iii) increased reactive oxygen species (ROS) and senescence-associated secretory phenotype (SASP) expression. Finally, dysfunctional autophagy, a process occurring during aging, contributes to altering brain homeostasis. The brains of mammals can be studied at cellular and subcellular levels to elucidate the mechanisms on the basis of age-related and degenerative disorders. The aim of this review is to summarize and update the most recent knowledge about brain aging through a comparative approach, where similarities and differences in some mammalian species are considered. [ABSTRACT FROM AUTHOR]

Background and objectives: Up to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known central nervous system (CNS) antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and cerebrospinal fluid (CSF) using neurons and astrocytes derived from human-induced pluripotent stem cells (hiPSCs). Methods: Human iPSC-derived astrocytes or neurons were incubated with serum/CSF from 99 patients [42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND)]. The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/ paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG binding to fixed CNS cells was detected using fluorescently-labeled antibodies and analyzed through automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout. Results: Using our CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 subjects. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases, and to both cell types in two cases, as confirmed by microscopy single-cell analyses. Highlighting the significance of our comprehensive 96-well CBA assay, neural-specific antibody binding was more frequent in IND (15 of 42) than in NIND patients (4 of 57) (Fisher’s exact test, p = 0.0005). Two of four AQP4+ NMO and four of seven definite AIE/PNS with intracellular-reactive antibodies [1 GFAP astrocytopathy, 2 Hu+, 1 Ri+ AIE/PNS)], as identified in diagnostic laboratories, were also positive with our CBA. Most interestingly, we showed antibody-reactivity in two of six seronegative NMOSD, six of 12 probable AIE/PNS, and one of 13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC-detected antibody binding in 13 versus zero patients, respectively, establishing the specificity of the detected antibodies for neural tissue. Conclusion: Our unique hiPSC-based CBA allows for the testing of novel neuron-/astrocyte-reactive antibodies in patients with suspected immunemediated neurological syndromes, and negative testing in established routine laboratories, opening new perspectives in establishing a diagnosis of such complex diseases. [ABSTRACT FROM AUTHOR]

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling pathway plays an important role in various biological processes, including cell growth, proliferation, differentiation, and apoptosis. The PI3K/Akt-related signaling pathways have been extensively studied, and they regulate neural cells to exert different or similar functions. This study reviews the research progress on PI3K/Akt-related signaling pathways in apoptosis, autophagy, oxidative stress, neuroinflammation, and other pathophysiological mechanisms in neural cells. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Transdifferentiation is the conversion of a specific somatic cell into another cell type, bypassing a transient pluripotent state. This implies a faster method to generate cells of interest with the additional benefit of reduced tumorigenic risk for clinical use. Objective We describe protocols that use small molecules as direct conversion inducers, without the need for exogenous factors, to evaluate the potential of cell transdifferentiation for pharmacological and clinical applications. Methods In this systematic review, using PRISMA guidelines, we conducted a personalized search strategy in four databases (PubMed, Scopus, Embase, and Web Of Science), looking for experimental works that used exclusively small molecules for transdifferentiation of non-neural cell types into neural lineage cells. Results We explored the main biological mechanisms involved in direct cell conversion induced by different small molecules used in 33 experimental in vitro and in vitro transdifferentiation protocols. We also summarize the main characteristics of these protocols, such as the chemical cocktails used, time for transdifferentiation, and conversion efficiency. Conclusion Small molecules-based protocols for neuronal transdifferentiation are reasonably safe, economical, accessible, and are a promising alternative for future use in regenerative medicine and pharmacology.

Abstract Background Metastasis, the spread, and growth of malignant cells at secondary sites within a patient’s body, accounts for over 90% of cancer-related mortality. Breast cancer is the most common tumor type diagnosed and the leading cause of cancer lethality in women in the United States. It is estimated that 10–16% breast cancer patients will have brain metastasis. Current therapies to treat patients with breast cancer brain metastasis (BCBM) remain palliative. This is largely due to our limited understanding of the fundamental molecular and cellular mechanisms through which BCBM progresses, which represents a critical barrier for the development of efficient therapies for affected breast cancer patients. Methods Previous research in BCBM relied on co-culture assays of tumor cells with rodent neural cells or rodent brain slice ex vivo. Given the need to overcome the obstacle for human-relevant host to study cell-cell communication in BCBM, we generated human embryonic stem cell-derived cerebral organoids to co-culture with human breast cancer cell lines. We used MDA-MB-231 and its brain metastatic derivate MDA-MB-231 Br-EGFP, other cell lines of MCF-7, HCC-1806, and SUM159PT. We leveraged this novel 3D co-culture platform to investigate the crosstalk of human breast cancer cells with neural cells in cerebral organoid. Results We found that MDA-MB-231 and SUM159PT breast cancer cells formed tumor colonies in human cerebral organoids. Moreover, MDA-MB-231 Br-EGFP cells showed increased capacity to invade and expand in human cerebral organoids. Conclusions Our co-culture model has demonstrated a remarkable capacity to discern the brain metastatic ability of human breast cancer cells in cerebral organoids. The generation of BCBM-like structures in organoid will facilitate the study of human tumor microenvironment in culture.

Background: Metastasis, the spread, and growth of malignant cells at secondary sites within a patient's body, accounts for over 90% of cancer-related mortality. Breast cancer is the most common tumor type diagnosed and the leading cause of cancer lethality in women in the United States. It is estimated that 10–16% breast cancer patients will have brain metastasis. Current therapies to treat patients with breast cancer brain metastasis (BCBM) remain palliative. This is largely due to our limited understanding of the fundamental molecular and cellular mechanisms through which BCBM progresses, which represents a critical barrier for the development of efficient therapies for affected breast cancer patients. Methods: Previous research in BCBM relied on co-culture assays of tumor cells with rodent neural cells or rodent brain slice ex vivo. Given the need to overcome the obstacle for human-relevant host to study cell-cell communication in BCBM, we generated human embryonic stem cell-derived cerebral organoids to co-culture with human breast cancer cell lines. We used MDA-MB-231 and its brain metastatic derivate MDA-MB-231 Br-EGFP, other cell lines of MCF-7, HCC-1806, and SUM159PT. We leveraged this novel 3D co-culture platform to investigate the crosstalk of human breast cancer cells with neural cells in cerebral organoid. Results: We found that MDA-MB-231 and SUM159PT breast cancer cells formed tumor colonies in human cerebral organoids. Moreover, MDA-MB-231 Br-EGFP cells showed increased capacity to invade and expand in human cerebral organoids. Conclusions: Our co-culture model has demonstrated a remarkable capacity to discern the brain metastatic ability of human breast cancer cells in cerebral organoids. The generation of BCBM-like structures in organoid will facilitate the study of human tumor microenvironment in culture. [ABSTRACT FROM AUTHOR]

Some studies relate the use of pyriproxyfen (PPF) in drinking water with damage to embryonic neurodevelopment, including a supposed association with cases of microcephaly. However, the effects on neural cells and skull ossification in embryos remain unclear. This study aims to investigate the effects of PPF on the structure and ultrastructure of brain cells and its influence on the skull ossification process during embryonic development. Chicken embryos, used as an experimental model, were exposed to concentrations of 0.01 and 10 mg/l PPF at E1. The findings demonstrated that PPF led to notable ultrastructural alterations such as reduced cilia and microvilli of ependymal cells and damage to mitochondria, endoplasmic reticulum, Golgi bodies, and cell membranes in neural cells. The frequency of changes and the degree of these cell damage between the forebrain and midbrain were similar. PPF induced a reduction in fox3 transcript levels, specific for differentiation of neurons, and a reduction in the NeuN protein content related to mature neurons and dendritic branches. PPF impacted the ossification process of the skull, as evidenced by the increase in the ossified area and the decrease in inter-bone spacing. In conclusion, this study highlights the ability of PPF to affect neurodevelopmental processes by inducing ultrastructural damage to neural cells, concomitant with a reduction in NeuN and fox3 expression. This detrimental impact coupled with deficiencies in skull ossification can prevent the proper growth and development of the brain. [ABSTRACT FROM AUTHOR]

Background and objectivesUp to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known central nervous system (CNS) antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and cerebrospinal fluid (CSF) using neurons and astrocytes derived from human-induced pluripotent stem cells (hiPSCs).MethodsHuman iPSC-derived astrocytes or neurons were incubated with serum/CSF from 99 patients [42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND)]. The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG binding to fixed CNS cells was detected using fluorescently-labeled antibodies and analyzed through automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout.ResultsUsing our CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 subjects. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases, and to both cell types in two cases, as confirmed by microscopy single-cell analyses. Highlighting the significance of our comprehensive 96-well CBA assay, neural-specific antibody binding was more frequent in IND (15 of 42) than in NIND patients (4 of 57) (Fisher’s exact test, p = 0.0005). Two of four AQP4+ NMO and four of seven definite AIE/PNS with intracellular-reactive antibodies [1 GFAP astrocytopathy, 2 Hu+, 1 Ri+ AIE/PNS)], as identified in diagnostic laboratories, were also positive with our CBA. Most interestingly, we showed antibody-reactivity in two of six seronegative NMOSD, six of 12 probable AIE/PNS, and one of 13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC-detected antibody binding in 13 versus zero patients, respectively, establishing the specificity of the detected antibodies for neural tissue.ConclusionOur unique hiPSC-based CBA allows for the testing of novel neuron-/astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in established routine laboratories, opening new perspectives in establishing a diagnosis of such complex diseases.

Transition metal carbides and nitrides (MXenes) are crystal nanomaterials with a number of surface functional groups such as fluorine, hydroxyl, and oxygen, which can be used as carriers for proteins and drugs. MXenes have excellent biocompatibility, electrical conductivity, surface hydrophilicity, mechanical properties and easy surface modification. However, at present, the stability of most MXenes needs to be improved, and more synthesis methods need to be explored. MXenes are good substrates for nerve cell regeneration and nerve reconstruction, which have broad application prospects in the repair of nervous system injury. Regarding the application of MXenes in neuroscience, mainly at the cellular level, the long-term in vivo biosafety and effects also need to be further explored. This review focuses on the progress of using MXenes in nerve regeneration over the last few years; discussing preparation of MXenes and their biocompatibility with different cells as well as the regulation by MXenes of nerve cell regeneration in two-dimensional and three-dimensional environments in vitro. MXenes have great potential in regulating the proliferation, differentiation, and maturation of nerve cells and in promoting regeneration and recovery after nerve injury. In addition, this review also presents the main challenges during optimization processes, such as the preparation of stable MXenes and long-term in vivo biosafety, and further discusses future directions in neural tissue engineering.

Brain aging in mammals is characterized by morphological and functional changes in neural cells. Macroscopically, this process, leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron deficits, as well as behavioral disorders. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro, including cell cycle arrest, increased lysosomal activity, telomere shortening, oxidative stress, and DNA damage. The most common markers for senescence identification were identified in (i) proteins implicated in cell cycle arrest, such as p16, p21, and p53, (ii) increased lysosomal mass, and (iii) increased reactive oxygen species (ROS) and senescence-associated secretory phenotype (SASP) expression. Finally, dysfunctional autophagy, a process occurring during aging, contributes to altering brain homeostasis. The brains of mammals can be studied at cellular and subcellular levels to elucidate the mechanisms on the basis of age-related and degenerative disorders. The aim of this review is to summarize and update the most recent knowledge about brain aging through a comparative approach, where similarities and differences in some mammalian species are considered.

The key component of neuroprotection after cerebral ischemia–reperfusion (I–R) injury is mitochondrial improvement. By focusing on the function of mitochondrial biogenesis and ATP-sensitive potassium (mK–ATP) channels and inflammatory responses, the current study assessed the neuroprotective potentials of lemon essential oil, D-limonene (LIM), in rats with cerebral I–R injury.

Schizophrenia is a severe psychiatric disorder of neurodevelopmental origin that affects around 1% of the world's population. Proteomic studies and other approaches have provided evidence of compromised cellular processes in the disorder, including mitochondrial function. Most of the studies so far have been conducted on postmortem brain tissue from patients, and therefore, do not allow the evaluation of the neurodevelopmental aspect of the disorder. To circumvent that, we studied the mitochondrial and nuclear proteomes of neural stem cells (NSCs) and neurons derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients versus healthy controls to assess possible alterations related to energy metabolism and mitochondrial function during neurodevelopment in the disorder. Our results revealed differentially expressed proteins in pathways related to mitochondrial function, cell cycle control, DNA repair and neuritogenesis and their possible implication in key process of neurodevelopment, such as neuronal differentiation and axonal guidance signaling. Moreover, functional analysis of NSCs revealed alterations in mitochondrial oxygen consumption in schizophrenia-derived cells and a tendency of higher levels of intracellular reactive oxygen species (ROS). Hence, this study shows evidence that alterations in important cellular processes are present during neurodevelopment and could be involved with the establishment of schizophrenia, as well as the phenotypic traits observed in adult patients. Neural stem cells (NSCs) and neurons were derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients and controls. Proteomic analyses were performed on the enriched mitochondrial and nuclear fractions of NSCs and neurons. Whole-cell proteomic analysis was also performed in neurons. Our results revealed alteration in proteins related to mitochondrial function, cell cycle control, among others. We also performed energy pathway analysis and reactive oxygen species (ROS) analysis of NSCs, which revealed alterations in mitochondrial oxygen consumption and a tendency of higher levels of intracellular ROS in schizophrenia-derived cells. [ABSTRACT FROM AUTHOR]

Research demonstrated that folate deficiency in either the mother or father could impact the biological functions of the offspring's of neural cells. Folate deficiency can also impair the methionine cycle, thus contributing to the conversion of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), which could potentially cause damage to the central nervous system. The study focused on the effect of parental folate deficiency on neural cell apoptosis in offspring neonatal rats and whether it is mediated by the levels of SAM and SAH in brains. The experimental design was conducted by feeding female and male Sprague Dawley (SD) rats with either folate-deficient or folate-normal diets, sacrificing the offspring within 24 h and isolating their brain tissue. Rats were divided into four groups: the maternal-folate-deficient and paternal-folate-deficient (D-D) group; the maternal-folate-deficient and paternal-folate-normal (D-N) group; the maternal-folate-normal and paternal-folate-deficient (N-D) group; and the maternal-folate-normal and paternal-folate-normal (N-N) group. There was down-regulation of B-cell lymphoma 2 (Bcl-2) expression, up-regulation of Bcl-2-associated X protein (Bax) and Caspase-3 expression of neural cells, and pathological changes in the brain ultrastructure, as well as decreased SAM levels, increased SAH levels, and a decreased SAM/SAH ratio in the rat fetal brain via parental folate deficiency. In conclusion, parental folate deficiency could induce the apoptosis of neural cells in neonatal offspring rats, while biparental folate deficiency had the greatest effect on offspring, and the unilateral effect was greater in mothers than in fathers. This process may be mediated by the levels of SAM and SAH in the rat fetal brain. [ABSTRACT FROM AUTHOR]

Whereas the axons of the peripheral nervous system (PNS) spontaneously regenerate after an injury, the occurring regeneration is rarely successful because axons are usually directed by inappropriate cues. Therefore, finding successful ways to guide neurite outgrowth, in vitro, is essential for neurogenesis. Microfluidic systems reflect more appropriately the in vivo environment of cells in tissues such as the normal fluid flow within the body, consistent nutrient delivery, effective waste removal, and mechanical stimulation due to fluid shear forces. At the same time, it has been well reported that topography affects neuronal outgrowth, orientation, and differentiation. In this review, we demonstrate how topography and microfluidic flow affect neuronal behavior, either separately or in synergy, and highlight the efficacy of microfluidic systems in promoting neuronal outgrowth. [ABSTRACT FROM AUTHOR]

Abstract Background Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. Understanding the timepoints of disturbances during neural cell differentiation processes could lead to an insight into the development of the disorder. In this context, human brain organoids and neural cells differentiated from patient-derived induced pluripotent stem cells are of great interest as a model to study the developmental origins of the disease. Results Here we evaluated the differential expression of proteins of schizophrenia patient-derived neural progenitors (NPCs), early neurons, and brain organoids in comparison to healthy individuals. Using bottom-up shotgun proteomics with a label-free approach for quantitative analysis, we found multiple dysregulated proteins since NPCs, modified, and disrupted the 21DIV neuronal differentiation, and cerebral organoids. Our experimental methods have shown impairments in pathways never before found in patient-derived induced pluripotent stem cells studies, such as spliceosomes and amino acid metabolism; but also, those such as axonal guidance and synaptogenesis, in line with postmortem tissue studies of schizophrenia patients. Conclusion In conclusion, here we provide comprehensive, large-scale, protein-level data of different neural cell models that may uncover early events in brain development, underlying several of the mechanisms within the origins of schizophrenia.

The development of highly parallel and affordable high-throughput single-cell transcriptomics technologies has revolutionized our understanding of brain complexity. These methods have been used to build cellular maps of the brain, its different regions, and catalog the diversity of cells in each of them during development, aging and even in disease. Now we know that cellular diversity is way beyond what was previously thought. Single-cell transcriptomics analyses have revealed that cell types previously considered homogeneous based on imaging techniques differ depending on several factors including sex, age and location within the brain. The expression profiles of these cells have also been exploited to understand which are the regulatory programs behind cellular diversity and decipher the transcriptional pathways driving them. In this review, we summarize how single-cell transcriptomics have changed our view on the cellular diversity in the human brain, and how it could impact the way we study neurodegenerative diseases. Moreover, we describe the new computational approaches that can be used to study cellular differentiation and gain insight into the functions of individual cell populations under different conditions and their alterations in disease. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells' function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(N-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together. [ABSTRACT FROM AUTHOR]

The development of electroactive organic materials has been an unquestionable breakthrough for organic electronics, allowing for the design of polymer-based electrochromic and optoelectronic devices. Electroactive materials have been also considered as promising in the wide-field biomedical engineering, particularly considering their similarity with a living tissue in terms of elemental composition, surface morphology and mechanical properties. Electroactive materials are especially relevant in neural tissue engineering since the functionality of neural tissue is based on the transfer of electrical signals. Unfortunately, electroactive organic materials are also prone to bacterial colonization, which becomes as a considerable threat to patient’s health. In our group, we have been working on the development of biocompatible, antibacterial and conducting implant coatings based on conducting polymers [1] and diazonium-derived electroactive monolayers [2]. With the use of electrochemical techniques, we have fabricated a library of electroactive materials with various physicochemical characteristics, differing in the way how they interact with a living matter. Antimicrobial effects have been verified against model microorganisms: E. coli, S. aureus, and C. albicans, while the biocompatibility has been confirmed towards human neuroblastoma SH-SY5Y cells. Unique combination of biological activity of developed materials with their electroactivity allows for further enhancement of their modus operandi, through the possibility of applying electrical stimulation to facilitate treatment. In this way, the results of our work are a major step towards the development of advanced bio-optoelectronic-based therapies.

Pancreatic cancer (PC) is a cancer with a poor prognosis, and nerve growth factor (NGF) is involved in the pathogenesis of PC within the unknown exact role. Herein, SW1990 cells and PC12 cells were co-cultured using transwell co-culture system and subsequently revealed that NGF was overexpressed in SW1990 cells and promoted PC12 cell proliferation. Knockdown of NGF expression in SW1990 cells using lentiviral shRNA effectively inhibited NGF expression in SW1990 cells and reduced its stimulatory effect on PC12 cell proliferation. Additionally, NGF in SW1990 cells increased the expression of IL-6, dopamine, and c-FOS, as well as decreased the level of lactate dehydrogenase, in PC12 cells, whereas the inhibition of NGF expression significantly reduced the levels of IL-6, dopamine and c-FOS, indicating the critical role of IL-6/STAT3 signaling in PC progression. Finally, cell proliferation, migration, and invasion were assessed using cell counting kit-8, scratch, and Transwell assays, which showed that activated neurons promoted the proliferation, migration, invasion, and NGF secretion of SW1990 cells through the IL-6/STAT3 pathway. The results revealed that NGF secreted by PC cells played a pivotal role in PC progression via regulating activated neural cells-secreted IL-6, providing new theoretical insights for the treatment of PC.

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition of tumor tissues. The differently expressed genes among each cluster were identified by EdgeR. GO enrichment analysis was used to understand the roles of genes within the clusters. Pseudotime cell trajectory was used to reveal the molecular pathways underlying cell fate decisions and identify genes whose expression changed as the cells underwent transition. We applied CellPhoneDB to identify cell-cell interactions among the epithelial and neural cells in PNI-PCa.Results: Analysis of the ∼17,000 single-cell transcriptomes in three PNI prostate cancer tissues, we identified 12 major cell clusters, including neural cells and two epithelial subtypes with different expression profiles. We found that basal/intermediate epithelial cell subtypes highly expressed PCa progression-related genes, including PIGR, MMP7, and AGR2. Pseudotime trajectory analysis showed that luminal epithelial cells could be the initiating cells and transition to based/intermediate cells. Gene ontology (GO) enrichment analysis showed that pathways related to cancer progressions, such as lipid catabolic and fatty acid metabolic processes, were significantly enriched in basal/intermediate cells. Our analysis also suggested that basal/intermediate cells communicate closely with neural cells played a potential role in PNI-PCa progression.Conclusion: These results provide our understanding of PNI-PCa cellular heterogeneity and characterize the potential role of basal/intermediate cells in the PNI-PCa progression.

Brain abnormalities and congenital malformations have been linked to the circulating strain of Zika virus (ZIKV) in Brazil since 2016 during the microcephaly outbreak; however, the molecular mechanisms behind several of these alterations and differential viral molecular targets have not been fully elucidated. Here we explore the proteomic alterations induced by ZIKV by comparing the Brazilian (Br ZIKV) and the African (MR766) viral strains, in addition to comparing them to the molecular responses to the Dengue virus type 2 (DENV). Neural stem cells (NSCs) derived from induced pluripotent stem (iPSCs) were cultured both as monolayers and in suspension (resulting in neurospheres), which were then infected with ZIKV (Br ZIKV or ZIKV MR766) or DENV to assess alterations within neural cells. Large-scale proteomic analyses allowed the comparison not only between viral strains but also regarding the two- and three-dimensional cellular models of neural cells derived from iPSCs, and the effects on their interaction. Altered pathways and biological processes were observed related to cell death, cell cycle dysregulation, and neurogenesis. These results reinforce already published data and provide further information regarding the biological alterations induced by ZIKV and DENV in neural cells. [ABSTRACT FROM AUTHOR]

Whereas the axons of the peripheral nervous system (PNS) spontaneously regenerate after an injury, the occurring regeneration is rarely successful because axons are usually directed by inappropriate cues. Therefore, finding successful ways to guide neurite outgrowth, in vitro, is essential for neurogenesis. Microfluidic systems reflect more appropriately the in vivo environment of cells in tissues such as the normal fluid flow within the body, consistent nutrient delivery, effective waste removal, and mechanical stimulation due to fluid shear forces. At the same time, it has been well reported that topography affects neuronal outgrowth, orientation, and differentiation. In this review, we demonstrate how topography and microfluidic flow affect neuronal behavior, either separately or in synergy, and highlight the efficacy of microfluidic systems in promoting neuronal outgrowth.

MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells’ function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(N-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together.

Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord injury has a long period of disease progression and leads to complications that exert a lot of mental and economic pressure on patients. There are currently a large number of therapeutic strategies for treating spinal cord injury, which range from pharmacological and surgical methods to cell therapy and rehabilitation training. All of these strategies have positive effects in the course of spinal cord injury treatment. This review mainly discusses the problems regarding stem cell therapy for spinal cord injury, including the characteristics and action modes of all relevant cell types. Induced pluripotent stem cells, which represent a special kind of stem cell population, have gained impetus in cell therapy development because of a range of advantages. Induced pluripotent stem cells can be developed into the precursor cells of each neural cell type at the site of spinal cord injury, and have great potential for application in spinal cord injury therapy.

Aim. Search for optimal conditions for the formation of aggregates/spheroids by neural cells (NC) isolated from the brain tissue of rat fetuses. Study of behavioral characteristics of NC in culture as a part of three-dimensional aggregates/spheroids. Methods. Isolation of NC from fetal rat brain tissue; cell viability assessment; cultivation; immunocytochemical staining; NC proliferative activity assessment. Results. It was found that the conditions for the robust formation of aggregates are: 1) the presence of 10 % adult rat's blood serum in the cell culture medium, 2) the seeding cell density -- 1-4x106 cells/ml and 3) the initial cell viability higher than 20 %. Conclusions. The isolated rat fetuses brain cells, when cultured in the presence of 10 % serum and at concentrations above 1x106 cells/ml, spontaneously form multicellular aggregates. The structure of aggregates formed during short-term cultivation depends on the initial cell viability, and the size of aggregates depends on the initial viability and seeding densities of NC. The rat fetuses NC aggregates/spheroids contain stem/progenitor cells that can proliferate and differentiate. NC aggregates/spheroids form three-dimensional structures, in which favorable conditions are developed for the survival and adequate functioning of the committed and stem/progenitor NC. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential protective effect of hydrogen sulfide against neural cell damage induced by a high-concentration of adenosine triphosphate (ATP). Methods: PC12 cells were incubated with ATP in order to induce cell damage. The extracellular level of H2S and protein expression of cystathionine-ß-synthase (CBS) were determined. The PC12 cells pretreated with NaHS, aminooxyacetic acid (AOAA) and KN-62, prior to further incubation with ATP, and the effect of the treatments on cell viability was investigated. Results: High-concentration ATP induced cell death in PC12 cells, and this was accompanied by markedly increased contents of extracellular H2S and CBS expression (p < 0.05). The ATP-induced cytotoxicity was significantly compromised after pretreatment with H2S. (p < 0.05). The viability of PC12 cells pretreated with NaHS and AOAA was significantly higher than that of PC12 cells treated with ATP alone. In addition, the viability of ATP-treated PC12 cells was further markedly increased after pretreatment with NaHS and KN-62 (p < 0.05). Conclusion: ATP induced a concentration- and time-dependent cytotoxicity in PC12 cells via the endogenous H2S/CBS system. Supplementation with exogenous H2S mitigated the cell damage induced by high concentration of ATP via a specific mechanism which may be specifically related to P2X7R. [ABSTRACT FROM AUTHOR]

Abstract Background Very few studies have identified receptor molecules for dengue virus (DENV) on neural cells. This study was designed to identify putative receptor/(s) involved in entry of DENV-3 in human neural cells of various lineages; neuronal-SH-SY5Y, astroglial-U-87 MG and microglial-CHME-3 cells. Result Virus overlay protein binding assay, LC-MS/MS and SEQUEST identified prohibitin1/2 (PHB1/2) as interacting proteins on SH-SY5Y, CHME-3, and U-87 MG cells. Infection inhibition and siRNA assays confirmed the role of PHB1/2 in the entry of DENV-3 into SH-SY5Y and CHME-3 cells but not in U-87 MG cells. Indirect immunofluorescence and flow-cytometry demonstrated the presence of PHB1/2 on the surface of SH-SY5Y and CHME-3 cells. Co-immunoprecipitation and Western blot, as well as double labelling, reconfirmed the interaction between PHB1/2 and DENV-3 EDIII protein. Conclusion These observations together for the first time indicate that PHB1/2 may serve as a putative receptor for DENV-3 in SH-SY5Y and CHME-3 cells. The study provided insights into DENV-3 and neural cell interactions.

Nerve guidance channels (NGCs) promote cell‐extracellular matrix (ECM) interactions occurring within the nanoscale. However, studies focusing on the effects of nanophase topography on neural cell functions are limited, and mostly concentrated on the sub‐micron level (>100 nm) surface topography. Therefore, the aim of this study was to fabricate <100 nm sized structures on poly lactic‐co‐glycolic acid (PLGA) films used in NGC applications to assess the effects of nanophase topography on neural cell functions. For this purpose, nanopit surface arrays were fabricated on PLGA surfaces via replica molding method. The results showed that neural cell proliferation increased up to 65% and c‐fos protein expression increased up to 76% on PLGA surfaces having nanophase surface arrays compared to the control samples. It was observed that neural cells spread to a greater extend and formed more neurite extensions on the nanoarrayed surfaces compared to the control samples. These results were correlated with increased hydrophilicity and roughness of the nanophase PLGA surfaces, and point toward the promise of using nanoarrayed surfaces in NGC applications. [ABSTRACT FROM AUTHOR]

Engineering conductive 3D cell scaffoldings offer advantages toward the creation of physiologically relevant platforms with integrated real‐time sensing capabilities. Dopaminergic neural cells are encapsulated into graphene‐laden alginate microfibers using a microfluidic approach, which is unmatched for creating highly‐tunable microfibers. Incorporating graphene increases the conductivity of the alginate microfibers by 148%, creating a similar conductivity to native brain tissue. The cell encapsulation procedure has an efficiency of 50%, and of those cells, ≈30% remain for the entire 6‐day observation period. To understand how the microfluidic encapsulation affects cell genetics, tyrosine hydroxylase, tubulin beta 3 class 3, interleukin 1 beta, and tumor necrosis factor alfa are analyzed primarily with real‐time reverse transcription‐quantitative polymerase chain reaction and secondarily with enzyme‐linked immunosorbent assay, immediately after manufacturing, after encapsulation in polymer matrix for 6 days, and after encapsulation in the graphene‐polymer composite for 6 days. Preliminary data shows that the manufacturing process and combination with alginate matrix affect the expression of the studied genes immediately after manufacturing. In addition, the introduction of graphene further changes gene expressions. Long‐term encapsulation of neural cells in alginate and 6‐day exposure to graphene also leads to changes in gene expressions. [ABSTRACT FROM AUTHOR]

Brain injuries, and neurodegenerative diseases can result in significant disability, lowered quality of life, and mortality. Current treatments including autologous nerve grafts are insufficient. This work presents the creation of new biomimetic supramolecular assemblies as a scaffold for potential applications in neural tissue regeneration. It is composed of polyethylene glycol amide core-conjugated with a thiazole-based building block and a peptide sequence (RVYNMGKGKGFCVPRPLVVYR). This peptide sequence is derived from laminin, a basal membrane protein, and a component of the extracellular matrix of neuronal cells. The product formed was allowed to self-assemble and bound to polypyrrole by layer-by-layer assembly to impart conductive properties (Lam-PEG-thiazole-PPy) resulting in the formation of fibrillar assemblies as indicated by electron microscopy studies. Rheological studies demonstrated that incorporation of PPy resulted in higher storage modulus indicative of higher ability to store deformation energy. Culture of rat olfactory-bulb derived neurons with the assemblies demonstrated that the Lam-PEG-thiazole-PPy assemblies promoted cell proliferation and were able to interact favorably with the cells. After 10 days of culture with the assemblies interconnected networks could be visualized. Furthermore, electrical stimulation resulted in a significant increase in axonal outgrowths. Thus, the assemblies presented herein exhibit potential for applications as a novel scaffold for neural tissue engineering. [ABSTRACT FROM AUTHOR]

Spermatogonial stem cells (SSCs) because of its ability to be reprogrammed into embryonic-like stem cells (ELSCs) can be a new source of pluripotent stem cells which can play a promising role in regenerative medicine. In this study, SSCs were transdifferentiated into neuron-like cells (NLCs) using two-step differentiation protocol. pluripotency and germ cells markers were analyzed in SSCs and ELSCs. Also neural markers were analyzed in ELSCs and NLCs. Methods: Neonatal rat testes were mechanically dissected and digested then was cultured in DMEM supplemented with 15% FBS. The medium was replaced with DMEM containing LIF, mercaptoethanol, EGF, bFGF, and GDNF. After 5 weeks, ELSCs colonies appeared. SSCs and ELSCs were evaluated by Stra8, plzf (germ cells markers) Oct4, and sox2 (pluripotency markers) using qRT-PCR. The ELSCs colonies were isolated and cultured in DMEM containing 0.5 mM lithium chloride. In day 5, ELSCs transdifferentiated to NLC. They were evaluated using neural marker including Neurofilament 200 (NF-200), choline acetyltransferase (CAT), synaptophysin (Syp), Nestin (Nes), Neurogenin1 (NG1), Neurod1 (Nd1), and Neurofilament 68 (NF-68)gene expression. Results: Result showed increasing expression of Oct4 and sox2 genes and low level of Stra8 and plzf expression in ELSCs than SSCs. After neural transdifferentiation by lithium chloride induction, neural markers were examined by RT-PCR in ELSCs and NLCs. The result showed expression of NF-200, CAT, Syp, Nes, NG1, Nd1 and NF-68 in NLCs opposed to ELSCs. Conclusion: This study indicates lithium chloride can promote ELSCs to transdifferentiate into NLCs. [ABSTRACT FROM AUTHOR]

Electromagnetic fields (EMFs) could induce oxidative stress (OS) in human tissues. Lipid peroxidation (LPO) is the main hallmark of OS that harms neural cell components, primarily lipids in the myelin sheaths and membranes. Vitamin E is a lipophilic antioxidant that protects cells from OS-related damages and inhibits the LPO process. In this study, male rats were assigned into three groups of Control, EMF, and EMF+ Vitamin E. The EMF producer equipment produced an alternate current of 50 Hz, 3 Mili Tesla (mT). At the end of the experiment, half of the substantia nigra in every sample was used for measurement of the malondialdehyde (MDA) level as the end-product of the LPO and activity of superoxide dismutase (SOD) enzyme. The next half of the tissue was prepared for transmission electron microscopy (TEM). In the EMF group, MDA level was enhanced and SOD value decreased significantly compared to the control group, but Vitamin E could restore these changes. In rats undergone EMF, heterochromatic nucleus and destruction in some portions of the nuclear membrane were detected. The segmental separation or destruction of myelin sheath lamellae was observed in nerve fibers. In treated animals, the nucleus was round, less heterochromatic, with a regular membrane. Separation of myelin sheath lamellae in some nerve fibers was slighter than the radiation group. Considering the results, EMF exposure induces LPO and triggers ultrastructural changes in the cell membranes, nucleus, and myelin sheath of substantia nigra cells, but Vitamin E consumption weakens these neuropathological alterations. [ABSTRACT FROM AUTHOR]

DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease.

Patients with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection manifest mainly respiratory symptoms. However, clinical observations frequently identified neurological symptoms and neuropsychiatric disorders related to COVID‐19 (Neuro‐SARS2). Accumulated robust evidence indicates that Neuro‐SARS2 may play an important role in aggravating the disease severity and mortality. Understanding the neuropathogenesis and cellular mechanisms underlying Neuro‐SARS2 is crucial for both basic research and clinical practice to establish effective strategies for early detection/diagnosis, prevention, and treatment. In this review, we comprehensively examine current evidence of SARS‐CoV‐2 infection in various neural cells including neurons, microglia/macrophages, astrocytes, pericytes/endothelial cells, ependymocytes/choroid epithelial cells, and neural stem/progenitor cells. Although significant progress has been made in studying Neuro‐SARS2, much remains to be learned about the neuroinvasive routes (transneuronal and hematogenous) of the virus and the cellular/molecular mechanisms underlying the development/progression of this disease. Future and ongoing studies require the establishment of more clinically relevant and suitable neural cell models using human induced pluripotent stem cells, brain organoids, and postmortem specimens. [ABSTRACT FROM AUTHOR]

The field of bioelectrochemistry is growing rapidly and is beginning to have a significant impact on the practice of medicine and biology. Due to its potency, electrochemical impedance spectroscopy (EIS) is used frequently by the scientists working at the interface between biology, medicine and electrochemistry. The aim of this paper is to describe the current state of the art devoted to the application of EIS in neural science, with the particular focus on the application of the impedance measurements to monitor cell adhesion, cell growth and morphological changes during neuronal differentiation, to track cell apoptosis, neural degeneration, and to distinguish among specific types of cells. These applications are investigated in terms of the electrochemical behaviour of cells and tissues, including the description of equivalent circuits used for modelling the electrode-tissue interface. Therefore, this paper combines the potential applications of EIS in neural science with the electrochemical background necessary for the proper interpretation of acquired results.

Duloxetine is a clinical drug that is primarily used for treatment of depression and pain, but it has side effects of addiction and tolerance. Cytochrome P450 (CYP) is its metabolic enzyme, and the drug's biofunction results from its neuro-protective effect in animal and cell models. We aimed to investigate the duloxetine-induced neural cytotoxicity effect and its performance in an N2a cell neurite outgrowth model. Cell death was assessed as cell viability using a Cell Count Kit-8 and further evaluated using bright-field images, propidium iodide (PI) and annexin V staining, colony-formation analysis, TUNEL staining of the cells, and biochemical testing. N2a cells were committed to differentiation by serum withdrawal and RA induction, and the neurite outgrowth was evaluated as the number of differentiated cells, longest neurite length, and average neurite length. Cell cycle analysis, PI and annexin V staining, mRNA expression, and biochemical testing were used to evaluate the drug effects on differentiation. The induction of neural cell death by duloxetine was not affected by classic cell death inhibitors but was promoted by the CYP inducer rifampicin. N2a cell neurite outgrowth was promoted by duloxetine via reduction of the CYP2D6 and MDA levels and induction of Bdnf protein levels. Duloxetine induces neural cell death through effects on CYP and promotes N2a cell neurite outgrowth by regulating CYP, Bdnf protein, and the intracellular lipid peroxidation level. [ABSTRACT FROM AUTHOR]

Background: Very few studies have identified receptor molecules for dengue virus (DENV) on neural cells. This study was designed to identify putative receptor/(s) involved in entry of DENV-3 in human neural cells of various lineages; neuronal-SH-SY5Y, astroglial-U-87 MG and microglial-CHME-3 cells. Result: Virus overlay protein binding assay, LC-MS/MS and SEQUEST identified prohibitin1/2 (PHB1/2) as interacting proteins on SH-SY5Y, CHME-3, and U-87 MG cells. Infection inhibition and siRNA assays confirmed the role of PHB1/2 in the entry of DENV-3 into SH-SY5Y and CHME-3 cells but not in U-87 MG cells. Indirect immunofluorescence and flow-cytometry demonstrated the presence of PHB1/2 on the surface of SH-SY5Y and CHME-3 cells. Co-immunoprecipitation and Western blot, as well as double labelling, reconfirmed the interaction between PHB1/2 and DENV-3 EDIII protein. Conclusion: These observations together for the first time indicate that PHB1/2 may serve as a putative receptor for DENV-3 in SH-SY5Y and CHME-3 cells. The study provided insights into DENV-3 and neural cell interactions. [ABSTRACT FROM AUTHOR]

Short oligomeric peptides typically do not exhibit the entanglements required for the formation of nanofibers via electrospinning. In this study, the synthesis of nanofibers composed of tyrosine‐based dipeptides via electrospinning, has been demonstrated. The morphology, mechanical stiffness, biocompatibility, and stability under physiological conditions of such biodegradable nanofibers were characterized. The electrospun peptide nanofibers have diameters less than 100 nm and high mechanical stiffness. Raman and infrared signatures of the peptide nanofibers indicate that the electrostatic forces and solvents used in the electrospinning process lead to secondary structures different from self‐assembled nanostructures composed of similar peptides. Crosslinking of the dipeptide nanofibers using 1,6‐diisohexanecyanate (HMDI) improved the physiological stability, and initial biocompatibility testing with human and rat neural cell lines indicate no cytotoxicity. Such electrospun peptides open up a realm of biomaterials design with specific biochemical compositions for potential biomedical applications such as tissue repair, drug delivery, and coatings for implants. [ABSTRACT FROM AUTHOR]

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Neurodegenerative diseases are a group of debilitating pathologies in which neuronal tissue dies due to the buildup of neurotoxic plaques, resulting in detrimental effects on cognitive ability, motor control, and everyday function. Stem cell technology offers promise in addressing this problem on multiple fronts, but the conventional sourcing of pluripotent stem cells involves harvesting from aborted embryonic tissue, which comes with strong ethical and practical concerns. The keystone discovery of induced pluripotent stem cell (iPSC) technology provides an alternative and endless source, circumventing the unfavorable issues with embryonic stem cells, and yielding fundamental advantages. This review highlights iPSC technology, the pathophysiology of two major neurodegenerative diseases, Alzheimer’s and Parkinson’s, and then illustrates current state-of-the-art approaches towards the treatment of the diseases using iPSCs. The technologies discussed in the review emphasize in vitro therapeutic neural cell and organoid development for disease treatment, pathological modeling of neurodegenerative diseases, and 3D bioprinting as it applies to both.