Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

Exercise-induced analgesia (EIA) refers to the elevation of pain thresholds and reduction in sensitivity to noxious stimuli achieved through exercise training. As a non-pharmacological treatment strategy, exercise therapy has demonstrated positive effects on both acute and chronic pain. Increasing evidence indicates that modulation of glial cell activity is an important mechanism underlying analgesia. Spinal glial cells contribute to the development and maintenance of pathological pain by promoting pain signal transmission through inflammatory responses and synaptic remodeling. Exercise can differentially regulate microglia and astrocyte activity, inhibiting multiple inflammatory signaling pathways, such as P2X4/P2X7 purinergic receptors, brain-derived neurotrophic factor (BDNF)/phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR), interleukin (IL)-6/Janus kinase (JAK) 2/signal transducer and activator of transcription 3 (STAT3), p38-mitogen-activated protein kinases (MAPK), and Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), thereby reducing the release of pro-inflammatory cytokines, decreasing inflammatory and nociceptive hypersensitivity, and alleviating pathological pain. This review also summarized the effects of different exercise intensities, durations, and frequencies on glial cell responses in order to provide a theoretical foundation for optimizing exercise-based interventions for pathological pain conditions.
Humans ; Microglia/metabolism* ; Astrocytes/metabolism* ; Exercise/physiology* ; Signal Transduction ; Analgesia/methods* ; Spinal Cord/cytology* ; Exercise Therapy ; Pain Management/methods* ; Animals ; Brain-Derived Neurotrophic Factor/metabolism*

OBJECTIVES: To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus (DMH) during sevoflurane anesthesia emergence. METHODS: Forty-two male C57BL/6 mice were randomized into 6 groups (n=7) for assessing astrocyte activation in the dorsomedial hypothalamus (DMH) under sevoflurane anesthesia. Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression, and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging. For assessing optogenetic activation of astrocytes, another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation, and sevoflurane anesthesia emergence was compared using behavioral experiments. In the remaining two groups, electroencephalogram (EEG) recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors. Anesthesia induction and recovery were assessed by observing the righting reflex. EEG data were recorded under 2.0% sevoflurane to calculate the burst suppression ratio (BSR) and under 1.5% sevoflurane for power spectrum analysis. Immunofluorescence staining was performed to visualize the colocalization of GFAP-positive astrocytes with viral protein signals. RESULTS: Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased. During 2.0% sevoflurane anesthesia, the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time (P<0.05), and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR (P<0.001). Under 1.5% sevoflurane anesthesia, optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group (P<0.01). CONCLUSIONS Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction. These findings offer new insights into the mechanisms underlying anesthesia emergence and may provide a potential target for accelerating postoperative recovery and managing anesthesia-related complications.
Animals ; Astrocytes/physiology* ; Sevoflurane ; Mice, Inbred C57BL ; Mice ; Male ; Electroencephalography ; Anesthetics, Inhalation/pharmacology* ; Hypothalamus/cytology* ; Anesthesia Recovery Period ; Methyl Ethers/pharmacology*

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.
Animals ; Astrocytes/cytology* ; Axons/physiology* ; Cell Transplantation ; Disease Models, Animal ; Electric Stimulation ; Humans ; Microglia/cytology* ; Motor Neurons/cytology* ; Nerve Regeneration ; Neuroglia/cytology* ; Neuronal Plasticity ; Neurons/cytology* ; Oligodendroglia/cytology* ; Pyramidal Tracts/pathology* ; Recovery of Function ; Regenerative Medicine/methods* ; Spinal Cord Injuries/therapy*

Vascular endothelial growth factor (VEGF) was originally recognized as a substance predominantly with vascular permeability and angiogenesis. Recently, more and more evidence indicated that VEGF is expressed in the neurons of the developing and adult brains. Functional investigation demonstrated that VEGF shows several important effects on the neuronal development and physiological function. For example, VEGF accelerates the development of neurons and neural dendritic and axon growth. Besides, VEGF directly and acutely regulates the functions of multiple ion channels of the neuron membrane and changes neural excitability. In traumatic or ischemic injured brains, VEGF produces neuroprotection, enhances capacity of adult neurogenesis and transformation of astroglial cells into new neurons, which are fundamental basis for re-establishment of neural network. Based on the knowledge obtained from the literatures, we propose that VEGF may play very important roles in neural plasticity in the normal brain, and the reconstruction of neurovascular units and neural repair in the traumatic injured brain. This review mainly focuses on neural activity and repair roles of VEGF in adult mammalian brains. Further study on the mechanism of VEGF's neurobiological effects in the brain will be helpful for understanding the regulation of brain functions and developing new therapeutic strategy for prevention of neurodegeneration of the brain.
Animals ; Astrocytes ; cytology ; Brain Injuries ; physiopathology ; Humans ; Neurogenesis ; Neuronal Plasticity ; Neurons ; cytology ; Vascular Endothelial Growth Factor A ; physiology

Spinal microglia and astrocytes play an important role in mediating behavioral hypersensitive state following peripheral nerve injury. However, little is known about the expression patterns of activated microglia and astrocytes in the spinal dorsal horn. The aim of the present study was to investigate the spatial distribution of microglial and astrocytic activation in cervical, thoracic, lumbar and sacral segments of spinal dorsal horn following chronic constriction injury (CCI) of sciatic nerve. The hind paw withdrawal threshold (PWT) of wild type (WT), CX3CR1(YFP) and GFAP(YFP) transgenic mice to mechanical stimulation was determined by von Frey test. Immunofluorescence staining was used to examine the spatial distribution of microglial and astrocytic activation in the spinal dorsal horn. Following CCI, all the WT, CX3CR1(YFP) and GFAP(YFP) mice developed robust allodynia in the ipsilateral paw on day 3 after CCI, and the allodynia was observed to last for 14 days. In comparison with sham groups, the PWTs of CCI group animals were significantly decreased (P < 0.01, n = 6). On day 14 after CCI, CX3CR1(YFP)-GFP immunofluorescence intensity was significantly increased in the ipsilateral lumbar spinal dorsal horn of the CX3CR1(YFP) mice (P < 0.01, n = 6), but no detectable changes were observed in other spinal segments. Increased GFAP(YFP)-GFP immunofluorescence intensity was observed in the ipsilateral thoracic, lumbar and sacral spinal segments of the GFAP(YFP) mice on day 14 after CCI. Iba-1 and GFAP immunofluorescence staining in WT mice showed the same result of microglia and astrocyte activation on day 14 after CCI. CX3CR1(YFP)-GFP and GFAP(YFP)-GFP immunofluorescence signal was colocalized with microglial marker Iba-1 and astrocytic marker GFAP, respectively. Interestingly, on day 3 after CCI, Iba-1-immunoreactivity was significantly increased in the ipsilateral thoracic, lumbar and sacral spinal segments of WT mice, whereas the significant upregulation of GFAP-immunoreactivity restrictedly occurred in the ipsilateral lumbar spinal segment. These results suggest that microglial and astrocytic activation may be involved in the development and maintenance of secondary allodynia in mice with neuropathic pain.
Animals ; Astrocytes ; physiology ; Disease Models, Animal ; Hyperalgesia ; Mice ; Mice, Transgenic ; Microglia ; physiology ; Neuralgia ; Peripheral Nerve Injuries ; Sciatic Nerve ; injuries ; Spinal Cord Dorsal Horn ; cytology ; Up-Regulation

OBJECTIVETo evaluate the efficiency of a modified culture method for rat cerebral cortical astrocytes in vitro.

METHODSThe astrocytes derived from the cerebral cortex of 3-day-old Sprague-Dawley rats were first purified as described previously, then the cells were replanted at a low density. The culture flask was changed after 1 hour and substratum was replaced after 24 hours. Cells were syncretized to a monolayer, followed by cell passage. After three passages the cells were cultured in DMEM medium containing 10% fetal serum for a long period. The derivation of the cells was identified by immunofluorescent staining with anti-GFAP polyclonal antibodies.

RESULTSA variety of morphologically distinct astrocytes with many long processes and small cell bodies were obtained. Finally an astrocytic network occurred through cellular process connections. The immunofluorescent staining demonstrated the percentage of GFAP-positive cells was above 98%.

CONCLUSIONSThe modified culture method for astrocytes from rat cerebral tissue is reliable, with a high purity. The cultured astrocytes have a similar morphological development to those in vivo.

Animals ; Astrocytes ; physiology ; Cell Culture Techniques ; Cerebral Cortex ; cytology ; Female ; Glial Fibrillary Acidic Protein ; analysis ; Male ; Rats ; Rats, Sprague-Dawley

There are two types of cells in the central nervous systems (CNS) of mammals-neurons and glia. The structure and function of neurons have been thoroughly studied; while the role of glia in information processing has not been systematically studied because they cannot produce action potentials like neuron. During the past decades, glial cells were considered to play a supportive role in CNS instead of information processing. Recently, a variety of studies suggest that glial cells are actively involved in the regulation of brain function associated with neurons. Glial cells, especially astrocytes play important roles in different sensory processing. In the present article, we review the role of astrocytes in sensory processing in the CNS.
Animals ; Astrocytes ; cytology ; physiology ; Central Nervous System ; physiology ; Humans ; Sensation ; physiology ; Synapses ; physiology

BACKGROUNDNeural stem cells (NSCs) are a self-renewing and multipotent population of the central nervous system (CNS), which are active during development and maintain homeostasis and tissue integrity throughout life. Microglias are an immune cell population resident in the CNS, which have crucial physiological functions in the developing and adult CNS. This study aimed to investigate that whether microglia co-cultured with NSCs could promote astrogliogenesis from NSCs.

METHODSMicroglia and NSCs were co-cultured in 24-well insert plates. NSCs were plated in the bottom of the well and microglia in the insert. Fluorescent staining, Western blotting and RT-PCR were used to determine the effect of microglia on NSCs differentiation.

RESULTSCo-culture of microglia and NSCs promoted astrogliogenesis from NSCs. Several key genes, such as Notch 1, Notch 2, Notch 3, Hes 5, and NRSF were downregulated, while the critical genes Id1 and Id2 were upregulated. BMP2 and FGF2 were upregulated.

CONCLUSIONMicroglias act as a regulator of NSCs astrogliogenesis.

Animals ; Astrocytes ; cytology ; metabolism ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Blotting, Western ; Bone Morphogenetic Protein 2 ; genetics ; Cell Differentiation ; genetics ; physiology ; Cells, Cultured ; Coculture Techniques ; methods ; Fibroblast Growth Factor 2 ; genetics ; Inhibitor of Differentiation Protein 1 ; genetics ; Inhibitor of Differentiation Protein 2 ; genetics ; Microglia ; cytology ; metabolism ; Microscopy, Fluorescence ; Neural Stem Cells ; cytology ; metabolism ; Rats ; Repressor Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

Olfactory ensheathing cells (OECs) are a unique type of glia with common properties of astrocyte and Schwann cells. Cultured OECs have two morphological phenotypes, astrocyte-like OECs and Schwann cell-like OECs. Reversible changes have been found between these two morphological phenotypes. However, the molecular mechanism underlying the regulation of these reversible changes is still unknown. The aim of this paper is to establish a method for the morphology plasticity of cultured OECs, and investigate the underlying mechanism. Using the primary culture of OECs and immunocytochemistry, the morphology of OECs was observed under serum, serum free media or dB-cAMP drug treatment. Statistical analysis was performed to test differences among the percentages of OEC subtypes under these conditions. The results showed that under serum free media, (95.2±3.7)% of OECs showed Schwann cell-like morphology, and (4.8±3.7)% of OECs showed astrocyte-like morphology; however, under 10% serum media, (42.5±10.4)% of OECs exhibited Schwann cell-like morphology, and (57.5±10.4)% of OECs exhibited astrocyte-like morphology. When media was changed back to serum free media for 24 h, (94.8±5.0)% of OECs showed Schwann cell-like morphology, and (5.2±5.0)% of OECs showed astrocyte-like morphology. Furthermore, culture condition with or without serum did not affect the expression of OEC cell marker, p-75 and S-100. Finally, dB-cAMP, an analog of cAMP, through inhibiting the formation of F-actin stress fibers and focal adhesion, induced the morphology switch from astrocyte-like to Schwann cell-like morphology under serum condition, promoted the branches and the growth of processes. These results suggest that serum induces the morphology plasticity of cultured OECs, which is mediated by cytoplasmic cAMP level through regulating the formation of F-actin stress fibers and focal adhesion.
Animals ; Astrocytes ; cytology ; physiology ; Cells, Cultured ; Culture Media ; pharmacology ; Cyclic AMP ; physiology ; Male ; Neuroglia ; cytology ; physiology ; Olfactory Bulb ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Schwann Cells ; cytology ; physiology ; Serum ; physiology