Glial Cell Function Research Articles

Polygenic risk score analysis revealed shared genetic background in attention deficit hyperactivity disorder and narcolepsy

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n = 876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g., P-value threshold < 0.05, β [SE], 5.815 [1.774]; P = 0.002) and inattention domain (e.g., P-value threshold < 0.05, β [SE], 5.734 [1.761]; P = 0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.

The P2X7 Receptor: Central Hub of Brain Diseases.

The P2X7 receptor is a cation channel activated by high concentrations of adenosine triphosphate (ATP). Upon long-term activation, it complexes with membrane proteins forming a wide pore that leads to cell death and increased release of ATP into the extracellular milieu. The P2X7 receptor is widely expressed in the CNS, such as frontal cortex, hippocampus, amygdala and striatum, regions involved in neurodegenerative diseases and psychiatric disorders. Despite P2X7 receptor functions in glial cells have been extensively studied, the existence and roles of this receptor in neurons are still controversially discussed. Regardless, P2X7 receptors mediate several processes observed in neuropsychiatric disorders and brain tumors, such as activation of neuroinflammatory response, stimulation of glutamate release and neuroplasticity impairment. Moreover, P2X7 receptor gene polymorphisms have been associated to depression, and isoforms of P2X7 receptors are implicated in neuropsychiatric diseases. In view of that, the P2X7 receptor has been proposed to be a potential target for therapeutic intervention in brain diseases. This review discusses the molecular mechanisms underlying P2X7 receptor-mediated signaling in neurodegenerative diseases, psychiatric disorders, and brain tumors. In addition, it highlights the recent advances in the development of P2X7 receptor antagonists that are able of penetrating the central nervous system.

Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia.

Frontotemporal dementia is a heterogeneous neurodegenerative disorder characterized by neuronal loss in the frontal and temporal lobes. Despite progress in understanding which genes are associated with the aetiology of frontotemporal dementia, the biological basis of how mutations in these genes lead to cell loss in specific cortical regions remains unclear. In this work, we combined gene expression data for 16 772 genes from the Allen Institute for Brain Science atlas with brain maps of grey matter atrophy in symptomatic C9orf72, GRN and MAPT mutation carriers obtained from the Genetic Frontotemporal dementia Initiative study. No significant association was seen between C9orf72, GRN and MAPT expression and the atrophy patterns in the respective genetic groups. After adjusting for spatial autocorrelation, between 1000 and 5000 genes showed a negative or positive association with the atrophy pattern within each individual genetic group, with the most significantly associated genes being TREM2, SSBP3 and GPR158 (negative association in C9Orf72, GRN and MAPT respectively) and RELN, MXRA8 and LPA (positive association in C9Orf72, GRN and MAPT respectively). An overrepresentation analysis identified a negative association with genes involved in mitochondrial function, and a positive association with genes involved in vascular and glial cell function in each of the genetic groups. A set of 423 and 700 genes showed significant positive and negative association, respectively, with atrophy patterns in all three maps. The gene set with increased expression in spared cortical regions was enriched for neuronal and microglial genes, while the gene set with increased expression in atrophied regions was enriched for astrocyte and endothelial cell genes. Our analysis suggests that these cell types may play a more active role in the onset of neurodegeneration in frontotemporal dementia than previously assumed, and in the case of the positively associated cell marker genes, potentially through emergence of neurotoxic astrocytes and alteration in the blood–brain barrier, respectively.

Neuron-glia interactions: Molecular basis of alzheimer's disease and applications of neuroproteomics.

Neurodegenerative disorders present with progressive and irreversible degeneration of the neurons. Alzheimer's disease (AD) is one of the most common neurodegenerative disorders affecting 50 million people worldwide (2017), expected to be doubled every 20years. Primarily affected by age, AD is the cause for old-age dementia, progressive memory loss, dysfunctional thoughts, confusion, cognitive impairment and personality changes. Neuroglia formerly understood as "glue" of the brain neurons consists of macroglia (astrocytes and oligodendrocyte), microglia and progenitors NG2-glia, and constitute a large fraction of the mammalian brain. The primary functions of glial cells are to provide neurons with metabolic and structural support in the healthy brain; however, they attain a "reactive" state from the "resting" state upon challenged with a pathological insult such as a neurodegenerative cascade. Failure or defects in their homoeostatic functions (i.e. concentration of ions, neurotransmitters) ultimately jeopardize neurons with excitotoxicity and oxidative stress. Moreover, the most common clinical outcome of AD is the cognitive impairment and memory loss, which are attributed mainly by the accumulation of Aβ. Failure of glial cells to remove the Aβ toxic proteins accelerates the AD progression. The rapidly emerging proteomic techniques such as mass spectrometry (MS), cross-linking mass spectrometry, hydrogen deuterium trade mass spectrometry, protein foot printing and 2-DGE combined withLC-MS/MS present wide array of possibilities for the identification of differentially expressed proteins in AD.

Pathophysiological Mechanisms of Cognitive Impairment and Neurodegeneration by Toxoplasma gondii Infection.

Toxoplasma gondii is an obligate intracellular parasite considered one of the most successful pathogens in the world, owing to its ability to produce long-lasting infections and to persist in the central nervous system (CNS) in most warm-blooded animals, including humans. This parasite has a preference to invade neurons and affect the functioning of glial cells. This could lead to neurological and behavioral changes associated with cognitive impairment. Although several studies in humans and animal models have reported controversial results about the relationship between toxoplasmosis and the onset of dementia as a causal factor, two recent meta-analyses have shown a relative association with Alzheimer’s disease (AD). AD is characterized by amyloid-β (Aβ) peptide accumulation, neurofibrillary tangles, and neuroinflammation. Different authors have found that toxoplasmosis may affect Aβ production in brain areas linked with memory functioning, and can induce a central immune response and neurotransmitter imbalance, which in turn, affect the nervous system microenvironment. In contrast, other studies have revealed a reduction of Aβ plaques and hyperphosphorylated tau protein formation in animal models, which might cause some protective effects. The aim of this article is to summarize and review the newest data in regard to different pathophysiological mechanisms of cerebral toxoplasmosis and their relationship with the development of AD and cognitive impairment. All these associations should be investigated further through clinical and experimental studies.

MeCP2 inhibits proliferation and migration of breast cancer via suppression of epithelial-mesenchymal transition.

Methyl‐CpG‐binding protein 2 (MeCP2) is an important epigenetic regulator for normal neuronal maturation and brain glial cell function. Additionally, MeCP2 is also involved in a variety of cancers, such as breast, prostate, lung, liver and colorectal. However, whether MeCP2 contributes to the progression of breast cancer remains unknown. In the present study, we investigated the role of MeCP2 in cell proliferation, migration and invasion in vitro. We found that knockdown of MeCP2 inhibited expression of epithelial‐mesenchymal transition (EMT)‐related markers in breast cancer cell lines. In conclusion, our study suggests that MeCP2 inhibits proliferation and invasion through suppression of the EMT pathway in breast cancer.

212-OR: Testosterone Deficiency Increases Hypothalamic Gliosis and Metabolic Risk

Obesity is associated with metabolic syndrome and gliosis, the activation of microglia (brain macrophages) and astrocytes, in the mediobasal hypothalamus (MBH) of humans and rodents. Similarly, hypogonadism in males is associated with increased susceptibility to weight gain, metabolic syndrome and MBH gliosis. Interventions that reduce glial activation in rodents result in protection from diet-induced obesity. Thus, we hypothesize that the combination of low testosterone and western diet causes gliosis, which in turn increases obesity susceptibility. To test this hypothesis in a rodent model, we combined gonadectomy (GDX) or sham surgery with high-fat diet (HFD) feeding in adult male mice. GDX and HFD feeding synergistically induced a striking activation of MBH astrocytes along with increased numbers of MBH microglia. This gliosis response was reversed to sham levels by testosterone replacement. After only 4 weeks of HFD feeding, differences in adiposity between GDX and sham groups were minimal with only a mild worsening of glucose tolerance. Thus, testosterone deficiency combined with HFD exposure elicits gliosis prior to substantial weight gain, suggesting a direct impact on glial cell function. To characterize the transcriptional response to testosterone deprivation and HFD exposure, we have developed mouse strains with GFP-tagged ribosomes (L10A) in astrocytes and microglia to allow purification of glial cell-specific mRNA from whole hypothalamic tissue samples (tagged ribosome affinity purification (TRAP)). In preliminary analyses, we have confirmed &amp;gt;10-fold enrichment of cell-specific mRNAs with de-enrichment of neuronal transcripts. These studies help reveal novel mechanisms by which hypogonadism increases the predisposition to metabolic disease. Disclosure M.D. Dorfman: None. J. Frey: None. K.M. Ness: None. A. Niraula: None. J.E. Kanter: None. K. Bornfeldt: None. K. Rubinow: None. E. Schur: None. J. Thaler: None. Funding American Heart Association (16SDG27010018); Diabetes Research Center (P30DK017047); Novo Nordisk (A116079); National Institutes of Health (R01DK119754)

Microtubule organization and dynamics in oligodendrocytes, astrocytes, and microglia.

Though much is known about microtubule organization and microtubule-based transport in neurons, the development and function of microtubules in glia are more enigmatic. In this review, we provide an overview of the literature on microtubules in ramified brain cells, including oligodendrocytes, astrocytes, and microglia. We focus on normal cell biology-how structure relates to function in these cells. In oligodendrocytes, microtubules are important for extension of processes that contact axons and for elongating the myelin sheath. Recent studies demonstrate that new microtubules can form outside of the oligodendrocyte cell body off of Golgi outpost organelles. In astrocytes and microglia, changes in cell shape and ramification can be influenced by neighboring cells and the extracellular milieu. Finally, we highlight key papers implicating glial microtubule defects in neurological injury and disease and discuss how microtubules may contribute to invasiveness in gliomas. Thus, future research on the mechanisms underlying microtubule organization in normal glial cell function may yield valuable insights on neurological disease pathology.

Activation and functional modulation of satellite glial cells by oxaliplatin lead to hyperexcitability of sensory neurons in vitro

Platinum-based chemotherapeutics still play an important role in cancer therapy, however, severe side effects, such as painful neuropathy, occur frequently. The pathophysiologic mechanisms depend on the applied chemotherapeutic agent and are still controversial. In addition to neuronal damage, disturbance of glial cell activity may contribute to neurotoxicity. Here, we focused on the effect of oxaliplatin on satellite glial cell (SGC) function and on the activity of the dorsal root ganglion (DRG) neurons. SGCs were isolated as high-purity cultures and treated with 1 and 10 μM oxaliplatin for 2, 4 and 24 h. Subsequently, glial fibrillary acid protein (GFAP), reactive oxygen species (ROS), Connexin-43 (Cx-43), and inward rectifier potassium channel 4.1 (Kir4.1) expression was determined by immunocytochemical staining (ICC) and Western blot analyses. Immunochemical staining and Western blot analysis showed an increase in the immune reactivity (IR) and protein levels of ROS, GFAP, and Cx-43. Furthermore, reduction of the IR and protein levels and current density were demonstrated using patch-clamp measurements, of Kir4.1 channels after oxaliplatin exposure. Cytokine release in SGCs was measured using enzyme-linked immunosorbent assays (ELISA) after oxaliplatin exposure and indicated an increased release of IL-6 and TNFα, while IL-1β was decreased. The direct influence of SGC-secreted factors in the supernatant after oxaliplatin treatment led to the hyperexcitability of cultured DRG neurons. In summary, oxaliplatin has a direct impact on the modulation and function of different SGC proteins. Furthermore, SGC-released factors influence the excitability of sensory neurons, qualifying SGCs as potential targets for the prevention and treatment of oxaliplatin-induced polyneuropathy.

Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation

There are sexual differences in the onset, prevalence, and outcome of numerous neurological diseases. Thus, in Alzheimer’s disease, multiple sclerosis, and major depression disorder, the incidence in women is higher than in men. In contrast, men are more likely to present other pathologies, such as amyotrophic lateral sclerosis, Parkinson’s disease, and autism spectrum. Although the neurological contribution to these diseases has classically always been studied, the truth is that neurons are not the only cells to be affected, and there are other cells, such as glial cells, that are also involved and could be key to understanding the development of these pathologies. Sexual differences exist not only in pathology but also in physiological processes, which shows how cells are differentially regulated in males and females. One of the reasons these sexual differences may occur could be due to the different action of sex hormones. Many studies have shown an increase in aromatase levels in the brain, which could indicate the main role of estrogens in modulating proinflammatory processes. This review will highlight data about sex differences in glial physiology and how estrogenic compounds, such as estradiol and tibolone, could be used as treatment in neurological diseases due to their anti-inflammatory effects and the ability to modulate glial cell functions.

Basigin Associates with Integrin in Order to Regulate Perineurial Glia and Drosophila Nervous System Morphology.

The Drosophila nervous system is ensheathed by a layer of outer glial cells, the perineurial glia, and a specialized extracellular matrix, the neural lamella. The function of perineurial glial cells and how they interact with the extracellular matrix are just beginning to be elucidated. Integrin-based focal adhesion complexes link the glial membrane to the extracellular matrix, but little is known about integrin's regulators in the glia. The transmembrane Ig domain protein Basigin/CD147/EMMPRIN is highly expressed in the perineurial glia surrounding the Drosophila larval nervous system. Here we show that Basigin associates with integrin at the focal adhesions to uphold the structure of the glia-extracellular matrix sheath. Knockdown of Basigin in perineurial glia using RNAi results in significant shortening of the ventral nerve cord, compression of the glia and extracellular matrix in the peripheral nerves, and reduction in larval locomotion. We determined that Basigin is expressed in close proximity to integrin at the glial membrane, and that expression of the extracellular integrin-binding domain of Basigin is sufficient to rescue peripheral glial compression. We also found that a reduction in expression of integrin at the membrane rescues the ventral nerve cord shortening, peripheral glial compression, and locomotor phenotypes, and that reduction in the integrin-binding protein Talin can partially rescue glial compression. These results identify Basigin as a potential negative regulator of integrin in the glia, supporting proper glial and extracellular matrix ensheathment of the nervous system.SIGNIFICANCE STATEMENT The glial cells and extracellular matrix play important roles in supporting and protecting the nervous system, but the interactions between these components have not been well characterized. Our study identified expression of a conserved Ig superfamily protein, Basigin, at the glial membrane of Drosophila where it associates with the integrin-based focal adhesion complexes to ensure proper ensheathment of the CNS and PNS. Loss of Basigin in the glia results in an overall compression of the nervous system due to integrin dysregulation, which causes locomotor defects in the animals. This underlies the importance of glia-matrix communication for structural and functional support of the nervous system.

Elevated levels of Drosophila Wdr62 promote glial cell growth and proliferation through AURKA signalling to AKT and MYC

WD40-Repeat Protein 62 (WDR62) is required to maintain neural and glial cell populations during embryonic brain growth. Although elevated expression of WDR62 is frequently associated with several tumour types, potential effects of excess WDR62 on proliferative growth remain undefined. Here, we demonstrate that glia specific overexpression of WDR62 in Drosophila larval brains resulted in increased cell size, over-proliferation and increased brain volume, without overt disruption of tissue organization. We further demonstrate WDR62 promoted over-proliferation and brain overgrowth by activating AURKA and pAKT signalling to increase MYC function in glial cells. Together these data suggest WDR62 normally functions in the glial lineage to activate oncogenic signalling networks, promoting proliferation and brain overgrowth.

Multi‐omics Studies Reveal Altered Hippocampal N‐Glycosylation in High Fat Diet‐Induced Obese Mice

BackgroundObesity is a major public health issue afflicting over 93 million people in the US and is projected to continue increasing. Impairments of cognitive abilities such as memory loss and mood disorders such as depression and anxiety are debilitating conditions associated with obesity. N‐glycosylation, an essential posttranslational modification of proteins is required for hippocampal long‐term potentiation and memory consolidation. However, whether altered N‐glycosylation is a potential mechanism involved in impaired hippocampal functioning in obesity remains unknown.AimOur goal was to develop a multi‐omics platform including glycomics, proteomics, and transcriptomics to determine the impact of high‐fat‐diet (HFD) consumption on hippocampal N‐glycosylation and expression of cell surface receptors in the context of diet‐induced obesity.HypothesisWe hypothesize that in HFD‐induced obese mice abnormal hippocampal N‐glycosylation occurs, affecting cell surface expression and signaling of key receptors.MethodsC57BL/6J male mice were fed a HFD (45% fat) for 8 weeks to induce obesity or a low‐fat diet (LFD, 10% fat) as the lean control group. Mice were euthanized, and brain tissues collected. Hippocampi were surgically dissected and processed for glycomics, proteomics, glycoproteomics, and RT‐qPCR analysis. Hippocampal cell membrane fractions (MF) were obtained, and N‐glycans released and analyzed by nano‐Liquid Chromatography‐Mass Spectrometry (nanoLC‐MS). Peptides and glycopeptides derived from MF were analyzed by nano‐LC‐FusionOrbitrap MS. Expression level of glycosyltransferase genes were obtained by qPCR.ResultsThe N‐glycome of LFD‐fed mice was dominated by highly branched fucosylated and sialylated N‐glycans (61%) while in HFD‐fed obese mice these N‐glycans were significantly decreased (51%). Correspondingly, transcript analysis of the glycosyltransferases showed that MGAT2 gene, which encodes the enzyme responsible for initiating the synthesis of complex branched N‐glycans, was significantly decreased by 50% in hippocampi of HFD‐fed obese mice compared to lean controls. Our findings show a decrease in complex branched glycans on the hippocampal cell surface of HFD‐obese mice that may be due to the downregulation of the MGAT2 gene. Proteomics and glycoproteomic analysis revealed site‐specific occupancy of over hundreds of hippocampal cell surface receptors.ConclusionsOur results suggest that chronic consumption of HFD and induced obesity results in abnormal hippocampal cell surface N‐glycosylation, and a possible enzyme associated with the altered glycosylation phenotype was identified. Aberrant N‐glycosylation may contribute to altered neuronal or glial cell function. This approach may be useful to identify novel targets for the development of new treatments for obesity‐associated mood and cognitive deficits.Support or Funding InformationFunding from National Institutes of Health, NIDDK (award 5R21DK118379) to M.B.

Homeodomain-interacting protein kinase (Hipk) plays roles in nervous system and muscle structure and function.

Homeodomain-interacting protein kinases (Hipks) have been previously associated with cell proliferation and cancer, however, their effects in the nervous system are less well understood. We have used Drosophila melanogaster to evaluate the effects of altered Hipk expression on the nervous system and muscle. Using genetic manipulation of Hipk expression we demonstrate that knockdown and over-expression of Hipk produces early adult lethality, possibly due to the effects on the nervous system and muscle involvement. We find that optimal levels of Hipk are critical for the function of dopaminergic neurons and glial cells in the nervous system, as well as muscle. Furthermore, manipulation of Hipk affects the structure of the larval neuromuscular junction (NMJ) by promoting its growth. Hipk regulates the phosphorylation of the synapse-associated cytoskeletal protein Hu-li tai shao (Hts; adducin in mammals) and modulates the expression of two important protein kinases, Calcium-calmodulin protein kinase II (CaMKII) and Partitioning-defective 1 (PAR-1), all of which may alter neuromuscular structure/function and influence lethality. Hipk also modifies the levels of an important nuclear protein, TBPH, the fly orthologue of TAR DNA-binding protein 43 (TDP-43), which may have relevance for understanding motor neuron diseases.

Elevated serum chemokine CCL22 levels in first-episode psychosis: associations with symptoms, peripheral immune state and in vivo brain glial cell function

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen’s d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (ρ = 0.20) and disorganization (ρ = 0.23), and with worse verbal performance (ρ = −0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [11C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (VT) of [11C]PBR28 was lower in patients compared to controls (p = 0.026; Cohen’s d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.

Neuron-glia interaction in the Drosophila nervous system.

Animals are able to move and react in manifold ways to external stimuli. Thus, environmental stimuli need to be detected, information must be processed, and, finally, an output decision must be transmitted to the musculature to get the animal moving. All these processes depend on the nervous system which comprises an intricate neuronal network and many glial cells. Glial cells have an equally important contribution in nervous system function as their neuronal counterpart. Manifold roles are attributed to glia ranging from controlling neuronal cell number and axonal pathfinding to regulation of synapse formation, function, and plasticity. Glial cells metabolically support neurons and contribute to the blood-brain barrier. All of the aforementioned aspects require extensive cell-cell interactions between neurons and glial cells. Not surprisingly, many of these processes are found in all phyla executed by evolutionarily conserved molecules. Here, we review the recent advance in understanding neuron-glia interaction in Drosophila melanogaster to suggest that work in simple model organisms will shed light on the function of mammalian glial cells, too.

Neuroinflammatory Gene Expression Alterations in Anterior Cingulate Cortical White and Gray Matter of Males With Autism Spectrum Disorder.

Evidence for putative pathophysiological mechanisms of autism spectrum disorder (ASD), including peripheral inflammation, blood–brain barrier disruption, white matter alterations, and abnormal synaptic overgrowth, indicate a possible involvement of neuroinflammation in the disorder. Neuroinflammation plays a role in the development and maintenance of the dendritic spines involved in glutamatergic and GABAergic neurotransmission, and also influences blood–brain permeability. Cytokines released from microglia can impact the length, location or organization of dendritic spines on excitatory and inhibitory cells as well as recruit and impact glial cell function around the neurons. In this study, gene expression levels of anti‐ and pro‐inflammatory signaling molecules, as well as oligodendrocyte and astrocyte marker proteins, were measured in both gray and white matter tissue in the anterior cingulate cortex from ASD and age‐matched typically developing (TD) control brain donors, ranging from ages 4 to 37 years. Expression levels of the pro‐inflammatory gene, HLA‐DR, were significantly reduced in gray matter and expression levels of the anti‐inflammatory gene MRC1 were significantly elevated in white matter from ASD donors as compared to TD donors, but neither retained statistical significance after correction for multiple comparisons. Modest trends toward differences in expression levels were also observed for the pro‐inflammatory (CD68, IL1β) and anti‐inflammatory genes (IGF1, IGF1R) comparing ASD donors to TD donors. The direction of gene expression changes comparing ASD to TD donors did not reveal consistent findings implicating an elevated pro‐ or anti‐inflammatory state in ASD. However, altered expression of pro‐ and anti‐inflammatory gene expression indicates some involvement of neuroinflammation in ASD. Autism Res 2020, 13: 870‐884. © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLCLay SummaryThe anterior cingulate cortex is an integral brain region in modulating social behaviors including nonverbal communication. The study found that inflammatory gene expression levels were altered in this brain region. We hypothesize that the inflammatory changes in this area could impact neuronal function. The finding has future implications in using these molecular markers to identify potential environmental exposures and distinct cell differences in autism.

Astrocyte mitochondria: Central players and potential therapeutic targets for neurodegenerative diseases and injury

Mitochondrial function has long been the focus of many therapeutic strategies for ameliorating age-related neurodegeneration and cognitive decline. Historically, the role of mitochondria in non-neuronal cell types has been overshadowed by neuronal mitochondria, which are responsible for the bulk of oxidative metabolism in the brain. Despite this neuronal bias, mitochondrial function in glial cells, particularly astrocytes, is increasingly recognized to play crucial roles in overall brain metabolism, synaptic transmission, and neuronal protection. Changes in astrocytic mitochondrial function appear to be intimately linked to astrocyte activation/reactivity found in most all age-related neurodegenerative diseases. Here, we address the importance of mitochondrial function to astrocyte signaling and consider how mitochondria could contribute to both the detrimental and protective properties of activated astrocytes. Strategies for protecting astrocytic mitochondrial function, promoting bidirectional transfer of mitochondria between astrocytes and neurons, and transplanting healthy mitochondria to diseased nervous tissue are also discussed.

β-amyloid and Oxidative Stress: Perspectives in Drug Development.

Alzheimer's Disease (AD) is a slow-developing neurodegenerative disorder in which the main pathogenic role has been assigned to β-amyloid protein (Aβ) that accumulates in extracellular plaques. The mechanism of action of Aβ has been deeply analyzed and several membrane structures have been identified as potential mediators of its effect. The ability of Aβ to modify neuronal activity, receptor expression, signaling pathways, mitochondrial function, and involvement of glial cells have been analyzed. In addition, extensive literature deals with the involvement of oxidative stress in Aβ effects. Herein we focus more specifically on the reciprocal regulation of Aβ, that causes oxidative stress, that favors Aβ aggregation and toxicity and negatively affects the peptide clearance. Analysis of this strict interaction may offer novel opportunities for therapeutic intervention. Both common and new molecules endowed with antioxidant properties deserve attention in this regard.

Glial Cells in Viral and Bacterial Infections

The Central nervous system consists of neurons and glial cells. Neurons constitute about half the volume of the CNS and glial cells make up the rest. They are also known as supporting cells of the nervous system. The three types of CNS supporting cells are Astrocytes, Oligodendrocytes and microglia. The supporting cells of Peripheral Nervous System are known as Schwann cells. The main functions of glial cells are to surround neurons, to supply nutrients and oxygen to neurons, to insulate one neuron from another and to destroy and remove the carcasses of dead neuron. Infection of the central nervous system represents a particular challenge to host defense due to its minimal immune surveillance and lack of typical lymphatic drainage (Carson and Sutcliffe, 1999). CNS resident cells must therefore be capable of mounting a quick and effective response to control an infection until cells of the peripheral adaptive immune system can be recruited. Keywords: Glial cells, viral infection, bacterial infection, immune system, glial cells Cite this Article Shilpi Priya. Glial Cells in Viral and Bacterial Infections. Research &amp; Reviews: A Journal of Immunology . 2020; 10(3): 13–21p.