Astrocytes In Central Nervous System Research Articles

Migraine and major depression: localizing shared genetic susceptibility in different cell types of the nervous systems.

There is a bidirectional relationship between migraine and major depression disorder (MDD). They likely share important risk genes associated with different cell types in the central nervous system (CNS) and peripheral nervous system (PNS). Profiling the expression of these genes in specific cell types is critical in understanding the pathophysiology of the relationship between migraine and MDD. Associated genes shared by migraine and MDD were identified by consolidating multiple curations of human disease-gene associations. Subsequently, the expression of overlapping genes was profiled and compared across the different cell types in CNS, PNS and neurovascular cells using eight single cell RNA sequencing datasets, including two human CNS datasets, two mouse CNS datasets, one human PNS dataset and three mouse PNS datasets. 45 shared genes between migraine and MDD were identified. Consistently found in all eight datasets, dopaminergic and serotonergic neurotransmitters were broadly expressed in CNS and PNS cell types. Glutamatergic and endocannabinoid genes were specifically expressed in CNS neurons and astrocytes. Synthesis and/or Release and Binding of Neuropeptides were specifically expressed in PNS peptidergic nociceptor (PEP). Genes related to inflammatory factors and immune responses were specifically expressed in CNS microglia. Among which, IL1B and COMT were highly expressed in CNS microglia cells. Single cell RNA sequencing of the CNS and PNS helps to identify the shared genes between migraine and MDD that are enriched in specific cell types. The findings provide new insight in understanding the underlying mechanism of action for the bidirectional co-morbidity between migraine and MDD.

Specialized astrocytes mediate glutamatergic gliotransmission in the CNS

Multimodal astrocyte–neuron communications govern brain circuitry assembly and function1. For example, through rapid glutamate release, astrocytes can control excitability, plasticity and synchronous activity2,3 of synaptic networks, while also contributing to their dysregulation in neuropsychiatric conditions4–7. For astrocytes to communicate through fast focal glutamate release, they should possess an apparatus for Ca2+-dependent exocytosis similar to neurons8–10. However, the existence of this mechanism has been questioned11–13 owing to inconsistent data14–17 and a lack of direct supporting evidence. Here we revisited the astrocyte glutamate exocytosis hypothesis by considering the emerging molecular heterogeneity of astrocytes18–21 and using molecular, bioinformatic and imaging approaches, together with cell-specific genetic tools that interfere with glutamate exocytosis in vivo. By analysing existing single-cell RNA-sequencing databases and our patch-seq data, we identified nine molecularly distinct clusters of hippocampal astrocytes, among which we found a notable subpopulation that selectively expressed synaptic-like glutamate-release machinery and localized to discrete hippocampal sites. Using GluSnFR-based glutamate imaging22 in situ and in vivo, we identified a corresponding astrocyte subgroup that responds reliably to astrocyte-selective stimulations with subsecond glutamate release events at spatially precise hotspots, which were suppressed by astrocyte-targeted deletion of vesicular glutamate transporter 1 (VGLUT1). Furthermore, deletion of this transporter or its isoform VGLUT2 revealed specific contributions of glutamatergic astrocytes in cortico-hippocampal and nigrostriatal circuits during normal behaviour and pathological processes. By uncovering this atypical subpopulation of specialized astrocytes in the adult brain, we provide insights into the complex roles of astrocytes in central nervous system (CNS) physiology and diseases, and identify a potential therapeutic target.

The role and potential therapeutic targets of astrocytes in central nervous system demyelinating diseases.

Astrocytes play vital roles in the central nervous system, contributing significantly to both its normal functioning and pathological conditions. While their involvement in various diseases is increasingly recognized, their exact role in demyelinating lesions remains uncertain. Astrocytes have the potential to influence demyelination positively or negatively. They can produce and release inflammatory molecules that modulate the activation and movement of other immune cells. Moreover, they can aid in the clearance of myelin debris through phagocytosis and facilitate the recruitment and differentiation of oligodendrocyte precursor cells, thereby promoting axonal remyelination. However, excessive or prolonged astrocyte phagocytosis can exacerbate demyelination and lead to neurological impairments. This review provides an overview of the involvement of astrocytes in various demyelinating diseases, emphasizing the underlying mechanisms that contribute to demyelination. Additionally, we discuss the interactions between oligodendrocytes, oligodendrocyte precursor cells and astrocytes as therapeutic options to support myelin regeneration. Furthermore, we explore the role of astrocytes in repairing synaptic dysfunction, which is also a crucial pathological process in these disorders.

The Correlation of Glial Fibrillary Acid Protein Level to Cognitive Function Outcome in Acute Lacunar Ischemic Stroke Patient

ABSTRACT :
 Introduction : Glial fibrillary acidic protein (GFAP) is a filamentous protein found in central nervous system astrocytes. Increased serum GFAP levels are caused by the process of astrogliosis after ischemic stroke and are associated with multisynaptic disorders so that they are at risk of causing cognitive disorders.
 Objective: To analyze the correlation between GFAP levels and cognitive function output in acute lacunar ischemic stroke patients.
 Research Methods : Analytical observational with prospective cohort approach. The subjects of this study were Acute lacunar ischemic stroke patients with mild to moderate NIHSS scores. Serum GFAP levels were taken at the onset of 48-72 hours of stroke. Cognitive function was measured using the Indonesian version of MoCA (MoCA Ina) test on the seventh and thirtieth day. Bivariate and multivariate analyzes were performed to assess the correlation between GFAP levels, cognitive functions and the confounding factors.
 Results: There was a significant correlation between GFAP levels and the MoCA Ina scores on the seventh day (r= -0.32, p=0.044), the thirtieth day (r= -0.398, p=0.011), and improvement in MoCA Ina scores (r= -0.342, p = 0.031). There was a significant correlation between GFAP levels on the executive domain on the seventh day (p= 0.01) and thirtieth day (p= 0.005), visuospatial on seventh day (p= 0.004) and thirtieth day (p= 0.016), language on the thirtieth day (p = 0.005), and memory on thirtieth day (p= 0.001). There was no significant correlation between GFAP levels and improvements in attentional, memory, language, visuospatial, and executive domains.
 Conclusion: There was a significant correlation between GFAP levels and MoCA Ina scores on the seventh, thirtieth day and the improvement of MoCA Ina scores. There was a significant correlation between GFAP levels with the executive, visuospatial, language, and memory domains.
 Keywords: cognitive, GFAP, lacunar ischemic stroke, MoCA Ina

In vivo astrocyte-to-neuron reprogramming for central nervous system regeneration: a narrative review.

The inability of damaged neurons to regenerate within the mature central nervous system (CNS) is a significant neuroscientific challenge. Astrocytes are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation, axon growth regulation, neuronal support, and higher cognitive functions such as memory. Recent reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional neurons. Building on in vitro work, many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost cells. However, many findings in this field are controversial, as the source of new neurons has been questioned. This review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury, brain injury, Huntington's disease, Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions.

Specific knockout of Sox2 in astrocytes reduces reactive astrocyte formation and promotes recovery after early postnatal traumatic brain injury in mouse cortex.

In response to central nervous system (CNS) injury, astrocytes go through a series of alterations, referred to as reactive astrogliosis, ranging from changes in gene expression and cell hypertrophy to permanent astrocyte borders around stromal cell scars in CNS lesions. The mechanisms underlying injury-induced reactive astrocytes in the adult CNS have been extensively studied. However, little is known about injury-induced reactive astrocytes during early postnatal development. Astrocytes in the mouse cortex are mainly produced through local proliferation during the first 2 weeks after birth. Here we show that Sox2, a transcription factor critical for stem cells and brain development, is expressed in the early postnatal astrocytes and its expression level was increased in reactive astrocytes after traumatic brain injury (TBI) at postnatal day (P) 7 in the cortex. Using a tamoxifen-induced hGFAP-CreERT2; Sox2flox/flox ; Rosa-tdT mouse model, we found that specific knockout of Sox2 in astrocytes greatly inhibited the proliferation of reactive astrocytes, the formation of glia limitans borders and subsequently promoted the tissue recovery after postnatal TBI at P7 in the cortex. In addition, we found that injury-induced glia limitans borders were still formed at P2 in the wild-type mouse cortex, and knockout of Sox2 in astrocytes inhibited the reactivity of both astrocytes and microglia. Together, these findings provide evidence that Sox2 is essential for the reactivity of astrocytes in response to the cortical TBI during the early postnatal period and suggest that Sox2-dependent astrocyte reactivity is a potential target for therapeutic treatment after TBI.

Regulation of wakefulness by astrocytes in the lateral hypothalamus

The lateral hypothalamus (LH) is an important brain region mediating sleep–wake behavior. Recent evidence has shown that astrocytes in central nervous system modulate the activity of adjacent neurons and participate in several physiological functions. However, the role of LH astrocytes in sleep–wake regulation remains unclear. Here, using synchronous recording of electroencephalogram/electromyogram in mice and calcium signals in LH astrocytes, we show that the activity of LH astrocytes is significantly increased during non-rapid eye movement (NREM) sleep-to-wake transitions and decreased during Wake-to-NREM sleep transitions. Chemogenetic activation of LH astrocytes potently promotes wakefulness and maintains long-term arousal, while chemogenetic inhibition of LH astrocytes decreases the total amount of wakefulness in mice. Moreover, by combining chemogenetics with fiber photometry, we show that activation of LH astrocytes significantly increases the calcium signals of adjacent neurons, especially among GABAergic neurons. Taken together, our results clearly illustrate that LH astrocytes are a key neural substrate regulating wakefulness and encode this behavior through surrounding GABAergic neurons. Our findings raise the possibility that overactivity of LH astrocytes may be an underlying mechanism of clinical sleep disorders.

Astrocyte-derived extracellular vesicles: novel biomarkers of CNS metal exposure and elimination with applications in discerning the pathogenesis of neurodegenerative diseases

Background and Aims: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, and though environmental exposure to metals has been associated with ALS, there are no existing biomarkers for these potentially causal environmental exposures – a biomarker for toxicant load in the central nervous system is greatly needed. Upon exposure to toxic metals in vitro, central nervous system (CNS) astrocytes, critical in metallohomeostasis, were observed to produce extracellular vesicles loaded with metals, potentially as a cellular elimination pathway. Metals are known to bioaccumulate in the CNS; EVs originating from the CNS (CNS-EVs) are readily found in peripherally drawn blood and can be isolated using cell-specific surface proteins. This study examines whether blood-borne CNS-EV metal cargoes can serve as reliable biomarkers of CNS metal exposure and reveal a link between metal metabolism and neurodegenerative disease (i.e., ALS). Methods: Precautions were undertaken to ensure EV protocols were completed under metal-free conditions. CNS-EVs were isolated from human whole blood and plasma samples via direct immunoprecipitation using biotinylated antibodies for proteins expressed on astrocytes. Once EVs were isolated, ELISA analysis generated protein concentrations, ViewSizer Nanoparticle Tracking analysis quantified abundance, and Transmission Electron Microscopy visualized particles. EVs were analyzed for metal contents using a Perkin-Elmer NexION 350S via an ICP-MS/MS dynamic reaction cell method. Results: Results demonstrate that it is feasible to quantify the small quantities of metals within these CNS-derived EVs, particularly in terms of toxic metals known to be associated with neurodegenerative disorders, including copper, zinc, lead, aluminum, manganese, and iron. Conclusions: CNS-derived EVs isolated from peripheral blood draws show promise as a potential biomarker of metal exposure and/or elimination in the brain and spinal cord, with promising applications in understanding the potential environmental pathogenesis of neurodegenerative disorders (i.e., ALS) among patients with relevant elevated CNS metal loads.

Immunofluorescent Evidence for Nuclear Localization of Aromatase in Astrocytes in the Rat Central Nervous System.

Estrogens regulate a variety of neuroendocrine, reproductive and also non-reproductive brain functions. Estradiol biosynthesis in the central nervous system (CNS) is catalyzed by the enzyme aromatase, which is expressed in several brain regions by neurons, astrocytes and microglia. In this study, we performed a complex fluorescent immunocytochemical analysis which revealed that aromatase is colocalized with the nuclear stain in glial fibrillary acidic protein (GFAP) positive astrocytes in cell cultures. Confocal immunofluorescent Z-stack scanning analysis confirmed the colocalization of aromatase with the nuclear DAPI signal. Nuclear aromatase was also detectable in the S100β positive astrocyte subpopulation. When the nuclear aromatase signal was present, estrogen receptor alpha was also abundant in the nucleus. Immunostaining of frozen brain tissue sections showed that the nuclear colocalization of the enzyme in GFAP-positive astrocytes is also detectable in the adult rat brain. CD11b/c labelled microglial cells express aromatase, but the immunopositive signal was distributed only in the cytoplasm both in the ramified and amoeboid microglial forms. Immunostaining of rat ovarian tissue sections and human granulosa cells revealed that aromatase was present only in the cytoplasm. This novel observation suggests a new unique mechanism in astrocytes that may regulate certain CNS functions via estradiol production.

Targetability of the neurovascular unit in inflammatory diseases of the central nervous system.

The blood-brain barrier (BBB) is a selectively permeable barrier separating the periphery from the central nervous system (CNS). The BBB restricts the flow of most material into and out of the CNS, including many drugs that could be used as potent therapies. BBB permeability is modulated by several cells that are collectively called the neurovascular unit (NVU). The NVU consists of specialized CNS endothelial cells (ECs), pericytes, astrocytes, microglia, and neurons. CNS ECs maintain a complex "seal" via tight junctions, forming the BBB; breakdown of these tight junctions leads to BBB disruption. Pericytes control the vascular flow within capillaries and help maintain the basal lamina. Astrocytes control much of the flow of material that has moved beyond the CNS EC layer and can form a secondary barrier under inflammatory conditions. Microglia survey the border of the NVU for noxious material. Neuronal activity also plays a role in the maintenance of the BBB. Since astrocytes, pericytes, microglia, and neurons are all able to modulate the permeability of the BBB, understating the complex contributions of each member of the NVU will potentially uncover novel and effective methods for delivery of neurotherapies to the CNS.

Light microscopic and heterogeneity analysis of astrocytes in the common marmoset brain.

Astrocytes are abundant cells of the central nervous system (CNS) and are involved in processes including synapse formation/function, ion homeostasis, neurotransmitter uptake, and neurovascular coupling. Recent evidence indicates that astrocytes show diverse molecular, structural, and physiological properties within the CNS. This heterogeneity is reflected in differences in astrocyte structure, gene expression, functional properties, and responsiveness to injury/pathological conditions. Deeper investigation of astrocytic heterogeneity is needed to understand how astrocytes are configured to enable diverse roles in the CNS. While much has been learned about astrocytic heterogeneity in rodents, much less is known about astrocytic heterogeneity in the primate brain where astrocytes have greater size and complexity. The common marmoset (Callithrix jacchus) is a promising non‐human primate model because of similarities between marmosets and humans with respect to genetics, brain anatomy, and cognition/behavior. Here, we investigated the molecular and structural heterogeneity of marmoset astrocytes using an array of astrocytic markers, multi‐label confocal microscopy, and quantitative analysis. We used male and female marmosets and found that marmoset astrocytes show differences in expression of astrocytic markers in cortex, hippocampus, and cerebellum. These differences were accompanied by intra‐regional variation in expression of markers for glutamate/GABA transporters, and potassium and water channels. Differences in astrocyte structure were also found, along with complex interactions with blood vessels, microglia, and neurons. This study contributes to our knowledge of the cellular and molecular features of marmoset astrocytes and is useful for understanding the complex properties of astrocytes in the primate CNS.

Inactivation of Hedgehog signal transduction in adult astrocytes results in region-specific blood–brain barrier defects

In this study, we use molecular genetic approaches to clarify the role of the Hedgehog (Hh) pathway in regulating the blood-brain/spinal cord barrier (BBB) in the adult mouse central nervous system (CNS). Our work confirms and extends prior studies to demonstrate that astrocytes are the predominant cell type in the adult CNS that transduce Hh signaling, revealed by the expression of Gli1, a target gene of the canonical pathway that is activated in cells receiving Hh, and other key pathway transduction components. Gli1+ (Hh-responsive) astrocytes are distributed in specific regions of the CNS parenchyma, including layers 4/5/6 of the neocortex, hypothalamus, thalamus, and spinal cord, among others. Notably, although BBB properties in endothelial cells are normally regulated by both paracellular and transcellular mechanisms, conditional inactivation of Hh signaling in astrocytes results in transient, region-specific BBB defects that affect transcytosis but not paracellular diffusion. These findings stand in contrast to prior studies that implicated astrocytes as a source of Sonic hedgehog that limited extravasation via both mechanisms [J. I. Alvarez et al., Science 334, 1727-1731 (2011)]. Furthermore, using three distinct Cre driver lines as well as pharmacological approaches to inactivate Hh-pathway transduction globally in CNS astrocytes, we find that these specific BBB defects are only detected in the rostral hypothalamus and spinal cord but not the cortex or other regions where Gli1+ astrocytes are found. Together, our data show that Gli1+ Hh-responsive astrocytes have regionally distinct molecular and functional properties and that the pathway is required to maintain BBB properties in specific regions of the adult mammalian CNS.

Exosomes Secreted by Microglia During Virus Infection in the Central Nervous System Activate an Inflammatory Response in Bystander Cells.

Microglia become persistently infected during Theiler’s murine encephalomyelitis virus (TMEV) infection in the central nervous system (CNS) of susceptible mice. We have previously shown that microglia infected with TMEV become activated through the innate immune receptors to express type I interferons, cytokines, and chemokines. Persistent TMEV infection in the CNS promotes chronic neuroinflammation and development of demyelinating disease similar to multiple sclerosis. In the current studies, we wanted to determine whether TMEV-infected microglia secrete exosomes which contribute to neuroinflammation in the CNS thus promoting the development of demyelinating disease. Exosomes are vesicles containing RNA, DNA, and proteins that are released from one cell and taken up by another cell to facilitate communication between cells. These studies isolated exosomes secreted by microglia during TMEV infection in vitro as well as exosomes secreted by microglia during early TMEV infection in mice. These studies show that microglia secrete exosomes during TMEV infection which contain the viral RNA coding region. The exosomes secreted by microglia during TMEV infection can be taken up by uninfected bystander cells, including CNS resident microglia, astrocytes, and neurons. The viral RNA in the exosomes can be transferred to the bystander cells. In addition, the bystander cells that took up these exosomes were activated through the innate immune response to express type I interferons, IFNα and IFNβ, pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and chemokines, CCL2. Most interestingly, exosomes secreted by microglia during early TMEV infection in mice activated an inflammatory response when transferred to the brains of naïve mice. These results show that exosomes secreted by microglia during early TMEV infection contain viral RNA and can activate uninfected bystander CNS cells to promote an inflammatory immune response. Thus, exosomes secreted by microglia during virus infection may promote viral persistence and neuroinflammation which contributes to the development of demyelinating disease.

Neuroprotective Effects of Physical Activity via the Adaptation of Astrocytes.

The multifold benefits of regular physical exercise have been largely demonstrated in human and animal models. Several studies have reported the beneficial effects of physical activity, both in peripheral tissues and in the central nervous system (CNS). Regular exercise improves cognition, brain plasticity, neurogenesis and reduces the symptoms of neurodegenerative diseases, making timeless the principle of “mens sana in corpore sano” (i.e., a healthy mind in a healthy body). Physical exercise promotes morphological and functional changes in the brain, acting not only in neurons but also in astrocytes, which represent the most numerous glial cells in the brain. The multiple effects of exercise on astrocytes comprise the increased number of new astrocytes, the maintenance of basal levels of catecholamine, the increase in glutamate uptake, the major release of trophic factors and better astrocytic coverage of cerebral blood vessels. The purpose of this review is to highlight the effects of exercise on brain function, emphasize the role of astrocytes in the healthy CNS, and provide an update for a better understanding of the effects of physical exercise in the modulation of astrocyte function.

Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia.

Cannabidiol (CBD) exhibits anti-inflammatory and neuroprotective properties and is suggested to be effective in the pre-clinical and clinical treatment of illnesses of the central nervous system (CNS). Two major types of CNS glial cells, astrocytes and microglia, play critical roles in the development and pathogenesis of CNS diseases. However, the mechanisms by which CBD plays an anti-inflammatory and neuroprotective role for these glial cells have not been fully elucidated. In this study, we examined the effects of CBD on the inflammatory response of mouse primary astrocytes and microglia. We also investigated whether the effect of CBD on cytokine release is mediated by the G protein coupled receptor 3 (GPR3), which was recently identified as a novel receptor for CBD. Our results showed that CBD inhibited inflammatory responses of astrocytes and microglia stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand in vitro and in vivo. In addition, CBD reduced the phosphorylation of STAT3 and NF-κB signaling pathways in LPS-stimulated astrocytes. However, the inhibitory effect of CBD on pro-inflammatory cytokine production was independent of GPR3 expression in both types of glial cells. Thus, although CBD is effective in ameliorating the activation of astrocytes and microglia, its mechanism of action still requires further study. Our data support the concept that CBD may have therapeutic potential for neurological disorders that involve neuroinflammation.

Downregulation of connexin43 potentiates noradrenaline-induced expression of brain-derived neurotrophic factor in primary cultured cortical astrocytes.

Decreased expression of brain-derived neurotrophic factor (BDNF) is involved in the pathology of depressive disorders. Astrocytes produce BDNF following antidepressant treatment or stimulation of adrenergic receptors. Connexin43 (Cx43) is mainly expressed in central nervous system astrocytes and its expression is downregulated in patients with major depression. How changes in Cx43 expression affect astrocyte function, including BDNF production, is poorly understood. The current study examined the effect of Cx43 knockdown on BDNF expression in cultured cortical astrocytes after stimulation of adrenergic receptors. The expression of Cx43 in rat primary cultured cortical astrocytes was downregulated with RNA interference. Levels of messenger RNAs (mRNAs) or proteins were measured by real-time PCR and western blotting, respectively. Knockdown of Cx43 potentiated noradrenaline (NA)-induced expression of BDNF mRNA in cultured astrocytes. NA treatment induced proBDNF protein expression in astrocytes transfected with small interfering RNA (siRNA) targeting Cx43, but not with control siRNA. This potentiation was mediated by the Src tyrosine kinase-extracellular signal-regulated kinase (ERK) pathway through stimulation of adrenergic α1 and β receptors. Furthermore, the Gq/11 protein-Src-ERK pathway and the G-protein coupled receptor kinase 2-Src-ERK pathway were involved in α1 and β adrenergic receptor-mediated potentiation of BDNF mRNA expression, respectively. The current studies demonstrate a novel mechanism of BDNF expression in cortical astrocytes mediated by Cx43, in which downregulation of Cx43 increases, through adrenergic receptors, the expression of BDNF. The current findings indicate a potentially novel mechanism of action of antidepressants, via regulation of astrocytic Cx43 expression and subsequent BDNF expression.

Neuroprotective Effects of Guanosine Supplementation in Experimental Models: A Systematic Review

Guanosine (GUO) is an endogenous guanine nucleoside to which several neuroprotective and neurotrophic effects have been attributed in experimental in vitro and/or in vivo models of central nervous system (CNS) diseases, including ischemic stroke, Alzheimer’s, Parkinson’s disease, spinal cord injury, nociception and depression. The objective of this work is to systematically review the neuroprotective effects of guanosine in experimental models in the CNS. The research was conducted through PubMed, Science direct, Scopus, Cochrane Library and SciELO (Scientific Electronic Library Online) and databases, where a number of relevant articles were found. Central nervous system (CNS) astrocytes release guanosine extracellularly, that has trophic effects. In the CNS, extracellular guanosine (GUO) stimulates mitosis, the synthesis of trophic factors and cell differentiation, including neuritogenesis, is neuroprotective and reduces apoptosis due to various stimuli. In this work we demonstrate that guanosine has a neuroprotective effect, through the survey of data that we carry out.

Research progress in pathogenesis and treatment of neuroinflammation

Neuroinflammation, defined as an inflammatory response mediated by central nervous system astrocyte, Microglia and endothelial cells, disrupts homeostasis and is typical of many Neurodegeneration. The DA receptor family is mainly expressed in Microglia, and microglia-induced neuroinflammation is an important pathogenesis of Neurodegeneration, this article reviews the pathogenesis and treatment of neuroinflammation.

Heterogeneity in the Number of Astrocytes in the Central Nervous System after Peritonitis.

Sepsis remains a major medical emergency that describes the body's systemic immune response to an infectious process and can lead to end-stage organ dysfunction and death. Clinical studies have introduced the concept of sepsis associated encephalopathy, which seems to have a plethora of cellular and molecular triggers starting from systemic inflammatory cytokines, blood-brain barrier (BBB) rupture, microscopic brain injury, altered cerebral circulation, neurotransmission, or even metabolic dysfunction. The purpose of our study is to reproduce the sepsis model previously described using the cecal ligature and puncture (CLP), and to take a closer look to the acute modifications that occur on cellular level when it comes to the brain-blood-barrier of the mice with systemic inflammation. After a rapid systemic response to peritonitis, we show a heterogeneity in astrocytic response within different cortical structures; hippocampus having the longest change in the number of GFAP+cells, while no difference was seen in the number of cortical astrocytes. With even more increasing roles of astrocytes in different pathologies, the relation between sepsis and astrocytes could prove a valuable in discovering new therapy in sepsis.

Neuroglia in Psychiatric Disorders.

In the twentieth century, neuropsychiatric disorders have been perceived solely from a neurone-centric point of view, which considers neurones as the key cellular elements of pathological processes. This dogma has been challenged thanks to the better comprehension of the brain functioning, which, even if far from being complete, has revealed the complexity of interactions that exist between neurones and neuroglia. Glial cells represent a highly heterogeneous population of cells of neural (astroglia and oligodendroglia) and non-neural (microglia) origin populating the central nervous system. The variety of glia reflects the innumerable functions that glial cells perform to support functions of the nervous system. Aberrant execution of glial functions contributes to the development of neuropsychiatric pathologies. Arguably, all types of glial cells are implicated in the neuropathology; however, astrocytes have received particular attention in recent years because of their pleiotropic functions that make them decisive in maintaining cerebral homeostasis. This chapter describes the multiple roles of astrocytes in the healthy central nervous system and discusses the diversity of astroglial responses in neuropsychiatric disorders suggesting that targeting astrocytes may represent an effective therapeutic strategy.