Neuronal Cell Markers Research Articles

Toe1 promotes proliferation and differentiation of neural progenitor cells

Toe1 (target of EGR1, member 1) is a 3′- exonuclease in the deadenylase family, essential for the maturation of small nuclear RNAs. Mutations in Toe1 are linked to pontocerebellar hypoplasia 7 (PCH7), a severe neurodegenerative syndrome affecting infants, characterized by progressive neurodegeneration, developmental delay, and genital abnormalities. The pathogenic mechanisms of PCH7 are unclear but are thought to involve abnormal neural stem cell (NSC) development during embryogenesis. This study investigates Toe1's role in NSC development using the C17.2 NSC line. Colony formation, EdU incorporation, and CFSE staining assays showed that Toe1 knockout inhibited C17.2 cell proliferation. Upon inducing differentiation, Toe1 knockout significantly reduced cell dendrites. Immunofluorescence, qPCR, and Western blot analyses indicated that Toe1 knockout suppressed the expression of neuronal marker βIII-tubulin and glial cell marker Gfap, thereby inhibiting C17.2 cell differentiation. Additionally, Toe1 knockout reduced the expression of Dll1 and Jag1, suggesting an inhibition of Notch signaling. High-throughput transcriptome sequencing revealed that Toe1 influenced calcium ion binding, ECM, and amino acid catabolism in undifferentiated C17.2 cells, and peptidase activity, chemotactic factors, ECM, and TNF signaling in differentiated cells. These findings underscore Toe1's critical regulatory role in NSC proliferation and differentiation, with significant implications for developing therapeutic targets for neurodegenerative diseases such as PCH7.

Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1. Responders have increased type I/II interferons and preexisting tissue resident (Trm) CD8 or Vδ1 γδ T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of public T-cell receptors. Spatial transcriptomics demonstrated colocalization of T cells with B and dendritic cells, which supply chemokines and costimulation. Lastly, ICB significantly increased clonal expansion or recruitment of Trm and Vδ1 cells in tumors specifically in responders, underscoring their therapeutic importance. These data identify potential clinically actionable biomarkers and therapeutic targets for MCC. Significance: MCC serves as a model of ICB response. We utilized the largest-to-date, multimodal MCC dataset (n = 116 patients) to uncover unique tumor-intrinsic properties and immune circuits that predict response. We identified CD8 Trm and Vδ1 T cells as clinically actionable mediators of ICB response in major histocompatibility complex-high and -low MCCs, respectively.

Biphenotypic Cells and α-Synuclein Accumulation in Enteric Neurons of Leucine-Rich Repeat Kinase 2 Knockout Mice.

Leucine-rich repeat kinase 2 is a molecule that is responsible for familial Parkinson's disease. Our previous findings revealed that leucine-rich repeat kinase 2 is expressed in the enteric nervous system. However, which cells in the enteric nervous system express leucine-rich repeat kinase 2 and whether leucine-rich repeat kinase 2 is associated with the structure of the enteric nervous system remain unclear. The enteric nervous system is remarkable because some patients with Parkinson's disease experience gastrointestinal symptoms before developing motor symptoms. We established a leucine-rich repeat kinase 2 reporter mouse model and performed immunostaining in leucine-rich repeat kinase 2 knockout mice. Longitudinal muscle containing the myenteric plexus prepared from leucine-rich repeat kinase 2 reporter mice was analyzed by immunostaining using anti-green fluorescent protein (GFP) antibody. Immunostaining using several combinations of antibodies characterizing enteric neurons and glial cells was performed on intestinal preparations from leucine-rich repeat kinase 2 knockout mice. GFP expression in the reporter mice was predominantly in enteric glial cells rather than in enteric neurons. Immunostaining revealed that differences in the structure and proportion of major immunophenotypic cells were not apparent in the knockout mice. Interestingly, the number of biphenotypic cells expressing the neuronal and glial cell markers increased in the leucine-rich repeat kinase 2 knockout mice. Moreover, there was accumulation of α-synuclein in the knockout mice. Our present findings suggest that leucine-rich repeat kinase 2 is a newly recognized molecule that potentially regulates the integrity of enteric nervous system and enteric α-synuclein accumulation.

Research on the shared function of central neurons and breast cancer based on gene expression profile data mining: The role of EMID1 protein antibody expression

In recent years, the incidence of breast cancer has gradually increased, and the research on it has become a hot spot in the scientific community. Central neurons play an important role in breast cancer. This study aims to explore the application of gene expression profile data mining in the study of shared function between central neurons and breast cancer, and focuses on the expression of EMID1 protein antibody. The study collected biomedical images and gene expression profile data of breast cancer patients. Then, we use image processing and analysis technology to extract and analyze features of biomedical images to obtain quantitative features of breast cancer. Gene expression profile data were preprocessed and analyzed to obtain information about breast cancer related genes. Integrating and fusing biomedical images and gene expression profile data, and exploring the sharing function between central neurons and breast cancer through data mining algorithms and statistical analysis methods. The results showed that the expression of EMID1 protein was high in breast cancer tissues, and the expression pattern was similar to that of central neurons. Further functional studies have shown that EMID1 protein is involved in the regulation of proliferation and invasion of breast cancer cells. By regulating the expression level of EMID1 protein, we observed that the proliferation and invasion ability of breast cancer cells were significantly affected. The research results show that through the comprehensive analysis of biomedical images and gene expression profile data, we found the sharing function between central neurons and breast cancer. The central neuronal cell marker genes EMID1 and GREB1L may be used as key biomarkers to regulate the pathogenesis of breast cancer and affect the occurrence and development of breast cancer.

SOX2 and SOX9 Expression in Developing Postnatal Opossum (Monodelphis domestica) Cortex.

(1) Background: Central nervous system (CNS) development is characterized by dynamic changes in cell proliferation and differentiation. Key regulators of these transitions are the transcription factors such as SOX2 and SOX9. SOX2 is involved in the maintenance of progenitor cell state and neural stem cell multipotency, while SOX9, expressed in neurogenic niches, plays an important role in neuron/glia switch with predominant expression in astrocytes in the adult brain. (2) Methods: To validate SOX2 and SOX9 expression patterns in developing opossum (Monodelphis domestica) cortex, we used immunohistochemistry (IHC) and the isotropic fractionator method on fixed cortical tissue from comparable postnatal ages, as well as dissociated primary neuronal cultures. (3) Results: Neurons positive for both neuronal (TUJ1 or NeuN) and stem cell (SOX2) markers were identified, and their presence was confirmed with all methods and postnatal age groups (P4-6, P6-18, and P30) analyzed. SOX9 showed exclusive staining in non-neuronal cells, and it was coexpressed with SOX2. (4) Conclusions: The persistence of SOX2 expression in developing cortical neurons of M. domestica during the first postnatal month implies the functional role of SOX2 during neuronal differentiation and maturation, which was not previously reported in opossums.

Expression, Significance, and Correlation of Histone Deacetylase 1/RE-1 Silencing Transcription Factor and Neuronal Markers in Glioma.

Inducing the differentiation of glioma cells into neuron-like cells may be an effective strategy to combat glioma. The histone deacetylase 1/RE-1 silencing transcription factor (HDAC1/REST) complex regulates the expression of multiple neuronal genes. In this study, we analyzed the presence and significance of this regulatory effect in glioma based on bioinformatics methods. The Human Protein Atlas database was used to obtain immunohistochemical staining images. The Gene Expression Profiling Interactive Analysis and Chinese Glioma Genome Atlas databases were used to analyze the expression of HDAC1/REST and neuronal markers in glioma, their effects on survival, and the association between HDAC1/REST and the expression of neuronal markers and stem cell markers. The differentially expressed genes between the high and low HDAC1/REST groups were explored. The Database for Annotation, Visualization and Integrated Discovery database was used for gene ontology and kyoto encyclopedia of genes and genomes pathway enrichment analysis. The results showed that the expression of HDAC1 and REST increased with the grade of glioma, while the expression of neuronal markers decreased with the grade of glioma. High expression of HDAC1/REST and low expression of neuronal markers were associated with poor prognosis. HDAC1/REST expression was negatively correlated with the expression of neuronal markers, and positively correlated with the expression of neural stem cell markers. The genes up-regulated in the high HDAC1/REST group were mainly related to extracellular matrix and inflammation, and the down-regulated genes were mainly related to synapsis. This study suggested that HDAC1/REST may be involved in maintaining the malignant phenotype of glioma cells and the stem cell status of glioma stem cells by inhibiting the expression of neuronal markers, which promote the progression of glioma.

Loss of Müller cell glutamine synthetase immunoreactivity is associated with neuronal changes in late-stage retinal degeneration.

A hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. The exact relationship between neurons and glia remodeling in this late stage of retinal degeneration, however, is unclear. This study assessed this by examining Müller cell dysfunction via glutamine synthetase immunoreactivity and its spatial association with retinal neuron subpopulations through various cell markers. Aged Rd1 mice retinae (P150 - P536, n = minimum 5 per age) and control heterozygous rd1 mice retinae (P536, n = 5) were isolated, fixed and cryosectioned. Fluorescent immunolabeling of glutamine synthetase was performed and retinal areas quantified as having low glutamine synthetase immunoreactivity if proportion of labeled pixels in an area was less than two standard deviations of the mean of the total retina. Other Müller cell markers such as Sox9 and Glial fibrillary acidic protein along with neuronal cell markers Calbindin, Calretinin, recoverin, Protein kinase C-α, Glutamic acid decarboxylase 67, and Islet-1 were then quantified within areas of low and normal synthetase immunoreactivity. Glutamine synthetase immunoreactivity was lost as a function of age in the rd1 mouse retina (P150 - P536). Immunoreactivity of other Müller cell markers, however, were unaffected suggesting Müller cells were still present in these low glutamine synthetase immunoreactive regions. Glutamine synthetase immunoreactivity loss affected specific neuronal populations: Type 2, Type 8 cone, and rod bipolar cells, as well as AII amacrine cells based on reduced recoverin, protein kinase Ca and parvalbumin immunoreactivity, respectively. The number of cell nuclei within regions of low glutamine synthetase immunoreactivity was also reduced suggesting possible neuronal loss rather than reduced cell marker immunoreactivity. These findings further support a strong interplay between glia-neuronal alterations in late-stage degeneration and highlight a need for future studies and consideration in intervention development.

63 Neuronal Death-associated Proteins S100B, Tau and Neuron Specific Enolase Association to Sepsis-related Organ Dysfunction and Death in the Elderly: A Prospective Single Center Cohort Study

Sepsis is a highly prevalent condition in the emergency department (ED) with high mortality, ICU admission and tracheal intubation rates. Its physiopathology is not fully understood, and how neuronal death-related cell markers relate is partially unknown. Our aim was to assess whether these markers are positively associated with worse outcomes in elderly septic patients.

Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.

The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.

Dysregulation of the Enteric Nervous System in the Mid Colon of Complement Component 3 Knockout Mice with Constipation Phenotypes.

Complement component 3 (C3) contributes to neurogenesis, neural migration, and synaptic elimination under normal and disease conditions of the brain, even though it has not been studied in the enteric nervous system (ENS). To determine the role of C3 in the regulatory mechanism of ENS during C3 deficiency-induced constipation, the changes in the markers of neuronal and interstitial cells of Cajal (ICCs), the markers for excitatory and inhibitory transmission of ENS, and expression of C3 receptors were analyzed in the mid colon of C3 knockout (KO) mice at 16 weeks of age. Prominent constipation phenotypes, including the decrease in stool parameters, changes in the histological structure, and suppression of mucin secretion, were detected in C3 KO mice compared to wildtype (WT) mice. The expression levels of the neuron specific enolase (NSE), protein gene product 9.5 (PGP9.5), and C-kit markers for myenteric neurons and ICCs were lower in the mid colon of C3 KO mice than WT mice. Excitatory transmission analysis revealed similar suppression of the 5-hydroxytryptamine (5-HT) concentration, expression of 5-HT receptors, acetylcholine (ACh) concentration, ACh esterase (AChE) activity, and expression of muscarinic ACh receptors (mAChRs), despite the mAChRs downstream signaling pathway being activated in the mid colon of C3 KO mice. In inhibitory transmission analysis, C3 KO mice showed an increase in the nitric oxide (NO) concentration and inducible nitric oxide synthase (iNOS) expression, while neuronal NOS (nNOS) expression, cholecystokinin (CCK), and gastrin concentration were decreased in the same mice. Furthermore, the levels of C3a receptor (C3aR) and C3bR expression were enhanced in the mid colon of C3 KO mice compared to the WT mice during C3 deficiency-induced constipation. Overall, these results indicate that a dysregulation of the ENS may play an important role in C3 deficiency-induced constipation in the mid colon of C3 KO mice.

Identification of Neuronal Cells in Sciatic Nerves of Adult Rats.

Prior research generally confirms that there are no neuronal cell bodies in the adult sciatic nerve. However, we occasionally find some neuronal cells in adult rat sciatic nerves, either intact or crush-injured. By whole-mount staining and optical imaging of the hyalinized sciatic nerves for Stmn2 (a specific marker for neuronal cells), we found those neuronal cells with irregular distribution in the sciatic nerves in both crushed model and normal rats. We investigated the identity of those cells and established a cultured sciatic nerve model. Immunohistochemistry evidence both in vivo and in vitro illustrated that some of those cells are mature neurons in sciatic nerves. With single-cell sequencing of neuronal cells in adeno-associated virus (AAV)-infected sciatic nerves, we identified that some of those cells are a kind of neuronal stem-like cells. Then we constructed a Nestin-CreERT2 rat line and traced those cells with fluorescence labeling which was induced by tamoxifen. Interesting, we proved that neuronal stem-like cells could proliferate by combination of EdU incorporation with staining in the sciatic nerves of transgenic rats. Together, the discovery of neuronal cells in adult sciatic nerves will make us aware of the distribution of neurons in the peripheral nervous system. Especially our data suggest that neuronal stem-like cells could proliferate in the sciatic nerves of adult rats.

Mitochondrial- and nuclear genome-controlled bioenergetic gene expression in Alzheimer's disease.

Mitochondrial dysfunction is a hallmark of brain aging and particularly accentuated in neurodegenerative diseases including Alzheimer's disease (AD), yet the regulation of mitochondrial DNA (mtDNA) versus nuclear DNA (nDNA)-encoded genes in the aging- and AD brains is largely unknown. Transcriptome datasets (ROSMAP, Mayo, and MSBB) and proteome dataset (ROSMAP) from cognitively normal and AD brains were analyzed. Linear regression models were applied to evaluate the association between mtDNA-encoded and nDNA-encoded genes at transcript and protein levels. Further, pathway analysis was performed to identify biological processes correlated with mtDNA-encoded gene expression. At transcript level, mtDNA encoded genes were uniformly regulated (average R2 ranging from 0.43 to 0.92) across all datasets analyzed. While mtDNA encoded and nDNA encoded oxidative phosphorylation (OXPHOS) genes were positively correlated at protein level, they were differentially regulated at transcript level. Compared to control brains, both genesets were downregulated in AD brains at protein level whereas at the transcript level, mtDNA transcript number was higher vs nDNA transcript number was lower. In addition, transcriptional correlations between nDNA OXPHOS genes and mtDNA genes were reduced in AD brains. In both normal and AD brains, mtDNA transcripts were consistently correlated with Alzheimer's related pathways, including a positive correlation with notch signaling module and negative correlations with synapse, mitochondrial, translation, and ubiquitin mediated protein clearance modules. Across brain cell types, neuronal cell markers were negatively correlated with mtDNA transcripts whereas markers for oligodendrocyte, astrocyte and endothelial cells exhibited positive correlations. Outcomes of these analyses suggest an underappreciated correlation between mitochondrial gene expression with the development of AD, in particular the coordinated transcriptional regulation across both the mitochondrial- and nuclear genomes. While mitochondria are a promising therapeutic target for Alzheimer's disease, the findings reported herein indicate that restoring optimal mitochondrial function to prevent or treat Alzheimer's remains a complex challenge. This work was supported by National Institute on Aging grants P01-AG026572, R01 AG057931, and R01 AG059093 to RDB.

Impaired neural differentiation of MPS IIIA patient induced pluripotent stem cell-derived neural progenitor cells

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterised by a progressive neurological decline leading to early death. It is caused by bi-allelic loss-of-function mutations in SGSH encoding sulphamidase, a lysosomal enzyme required for heparan sulphate glycosaminoglycan (HS GAG) degradation, that results in the progressive build-up of HS GAGs in multiple tissues most notably the central nervous system (CNS). Skin fibroblasts from two MPS IIIA patients who presented with an intermediate and a severe clinical phenotype, respectively, were reprogrammed into induced pluripotent stem cells (iPSCs). The intermediate MPS IIIA iPSCs were then differentiated into neural progenitor cells (NPCs) and subsequently neurons. The patient derived fibroblasts, iPSCs, NPCs and neurons all displayed hallmark biochemical characteristics of MPS IIIA including reduced sulphamidase activity and increased accumulation of an MPS IIIA HS GAG biomarker. Proliferation of MPS IIIA iPSC-derived NPCs was reduced compared to control, but could be partially rescued by reintroducing functional sulphamidase enzyme, or by doubling the concentration of the mitogen fibroblast growth factor 2 (FGF2). Whilst both control heparin, and MPS IIIA HS GAGs had a similar binding affinity for FGF2, only the latter inhibited FGF signalling, suggesting accumulated MPS IIIA HS GAGs disrupt the FGF2:FGF2 receptor:HS signalling complex. Neuronal differentiation of MPS IIIA iPSC-derived NPCs was associated with a reduction in the expression of neuronal cell marker genes βIII-TUBULIN, NF-H and NSE, revealing reduced neurogenesis compared to control. A similar result was achieved by adding MPS IIIA HS GAGs to the culture medium during neuronal differentiation of control iPSC-derived NPCs. This study demonstrates the generation of MPS IIIA iPSCs, and NPCs, the latter of which display reduced proliferation and neurogenic capacity. Reduced NPC proliferation can be explained by a model in which soluble MPS IIIA HS GAGs compete with cell surface HS for FGF2 binding. The mechanism driving reduced neurogenesis remains to be determined but appears downstream of MPS IIIA HS GAG accumulation.

Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets.

Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues.Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression.Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species.

Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and PKM2 as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation.

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed the relationships between vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and complement and coagulation cascades. Combinational verification with transcriptome and gene expression analysis of different cell types revealed fatty acids-related PPAR signaling pathway and pyruvate kinase isoform M2 (PKM2) as key markers of neuronal cells in response to OGD/R. These findings suggest that, although there remain some limitations to be improved, our ischemic stroke model using human cerebral organoids would be a potentially useful tool when combined with other conventional two-dimensional (2D) mono-culture systems.

Reduced adult neurogenesis is associated with increased macrophages in the subependymal zone in schizophrenia.

Neural stem cells in the human subependymal zone (SEZ) generate neuronal progenitor cells that can differentiate and integrate as inhibitory interneurons into cortical and subcortical brain regions; yet the extent of adult neurogenesis remains unexplored in schizophrenia and bipolar disorder. We verified the existence of neurogenesis across the lifespan by chartering transcriptional alterations (2 days-103 years, n = 70) and identifying cells indicative of different stages of neurogenesis in the human SEZ. Expression of most neural stem and neuronal progenitor cell markers decreased during the first postnatal years and remained stable from childhood into ageing. We next discovered reduced neural stem and neuronal progenitor cell marker expression in the adult SEZ in schizophrenia and bipolar disorder compared to controls (n = 29-32 per group). RNA sequencing identified increased expression of the macrophage marker CD163 as the most significant molecular change in schizophrenia. CD163+ macrophages, which were localised along blood vessels and in the parenchyma within 10 µm of neural stem and progenitor cells, had increased density in schizophrenia but not in bipolar disorder. Macrophage marker expression negatively correlated with neuronal progenitor marker expression in schizophrenia but not in controls or bipolar disorder. Reduced neurogenesis and increased macrophage marker expression were also associated with polygenic risk for schizophrenia. Our results support that the human SEZ retains the capacity to generate neuronal progenitor cells throughout life, although this capacity is limited in schizophrenia and bipolar disorder. The increase in macrophages in schizophrenia but not in bipolar disorder indicates that immune cells may impair neurogenesis in the adult SEZ in a disease-specific manner.

Varicella-Zoster Virus Infection of Neurons Derived from Neural Stem Cells.

Varicella-Zoster virus (VZV) is a human herpesvirus that causes varicella (chickenpox) as a primary infection, and, following a variable period of ganglionic latency in neurons, it reactivates to cause herpes zoster (shingles). An analysis of VZV infection in cultures of neural cells, in particular when these have been obtained from induced pluripotent stem cells (iPSCs) or neural stem cells consisting of highly purified neuronal cultures, has revealed much data that may be of neurobiological significance. Early studies of VZV infection of mature cultured neural cells were mainly descriptive, but more recent studies in homogeneous neural stem cell cultures have used both neuronal cell markers and advanced molecular technology. Two general findings from such studies have been that (a) VZV infection of neurons is less severe, based on several criteria, than that observed in human fibroblasts, and (b) VZV infection of neurons does not lead to apoptosis in these cells in contrast to apoptosis observed in fibroblastic cells. Insights gained from such studies in human neural stem cells suggest that a less severe initial lytic infection in neurons, which are resistant to apoptosis, is likely to facilitate a pathological pathway to a latent state of the virus in human ganglia.

The expression profile of miR-3099 during neural development of Ts1Cje mouse model of Down syndrome

MicroRNA-3099 (miR-3099) plays a crucial role in regulating neuronal differentiation and development of the central nervous system (CNS). The miR-3099 is a pro-neuronal miRNA that promotes neural stem/progenitor cell (NSPC) differentiation into neuronal lineage by suppressing astrogliogenesis. Down syndrome (DS) brain exhibited increased astrogliogenesis and reduced neuronal cell density. The involvement of miR-3099 in the neurodevelopment of DS has not been investigated and potentially responsible for the neurogenic-to-gliogenic shift phenomenon observed in DS brain. To investigate the role of miR-3099 during DS brain development, neural/progenitor cell proliferation and differentiation, we profiled miR-3099 expression level in the Ts1Cje, a mouse model for DS. We analysed the Ts1Cje whole brain at embryonic day (E) 10.5, E14.5 and P1.5, proliferating neurospheres and differentiating neurospheres at 3, 9 and 15 days in vitro (DIV). Expression of miR-3099 in both the developing mouse brain and the differentiating neurosphere was not significantly different between Ts1Cje and wild type controls. In contrast, the expression level of miR-3099 was significantly higher (p<0.05) in proliferating NSPC derived from the Ts1Cje compared to wild-type. Further molecular profiling of NPSC and glial cell markers indicated that the expression of Sox2 (p<0.01) and Gfap (p<0.05) were significantly downregulated in Ts1Cje neurospheres as compared to that of wild type, respectively. While there were no significant differences in Tuj1 and Nestin expression levels between the Ts1Cje and wild type neurospheres, their expression levels were ~3-fold upregulated and ~2.6 downregulated Ts1Cje group, respectively. The findings suggest that dysregulation of miR-3099 affects NSPC lineage commitment as indicated by altered postmitotic neuronal cell markers. Further molecular characterisation and gene expression profiling of other neuronal and glial markers will help refine the analysis of gene-gene interactions underlying the neuropathologies of DS.

Nerve and Glial Cell Expressions in the Testes and Epididymides of Different Age Groups of Cane Rat (Thryonomys swinderianus).

Purpose:This study was conducted to examine the variations in the expressions of neuronal and glial cell markers in the testes and epididymides of different age groups of cane rat using histochemical and immunohistochemical techniques.Method:Thirty (32) healthy domesticated male cane rats were used for this investigation. The rats were divided into four groups (prepubertal [≤4 months], pubertal (>4 ≤12 months), adult (>12 ≤30 months), and aged (>30 months)] of 8 animals each. Subsequent to anesthesia and intracardiac perfusion of the rats with 10% buffered formalin, testes were harvested and preliminary assessment of nervous and glial structures was determined using the Golgi technique. Specific immunolocalization was done using the anti-neurofilament (NF-20) and anti-glial fibrillary acid protein (GFAP) for the expressions of neuronal and astrocyte-like cells, respectively.Result:Neuronal and astrocyte-like structures as revealed by the Golgi procedure were demonstrated in the tunica albuginea and interstitium of the testes as well as in the periductal muscle coat and epididymal interstitium of the caput down to the caudal segments. Golgi signal intensities of the expressions in both testes and epididymides increased with age advancement. Immunolocalization of the nerve structures and glial cells tallied with the Golgi results. However, NF signal intensity was significantly higher in the adult relative to others. Similarly, GFAP signal intensity increased with age increment.Conclusion:This study has shown that the variation in the expression of neuronal and glial cells in the testis and epididymis of the cane rat could be associated with increased reproductive reproductive activity.

Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone.

SummaryAdult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.