Specialized Membrane Domains for Water Transport in Glial Cells: High-Resolution Immunogold Cytochemistry of Aquaporin-4 in Rat Brain

Membrane water transport is critically involved in brain volume homeostasis and in the pathogenesis of brain edema. The cDNA encoding aquaporin-4 (AQP4) water channel protein was recently isolated from rat brain. We used immunocytochemistry and high-resolution immunogold electron microscopy to identify the cells and membrane domains that mediate water flux through AQP4. The AQP4 protein is abundant in glial cells bordering the subarachnoidal space, ventricles, and blood vessels. AQP4 is also abundant in osmosensory areas, including the supraoptic nucleus and subfornical organ. Immunogold analysis demonstrated that AQP4 is restricted to glial membranes and to subpopulations of ependymal cells. AQP4 is particularly strongly expressed in glial membranes that are in direct contact with capillaries and pia. The highly polarized AQP4 expression indicates that these cells are equipped with specific membrane domains that are specialized for water transport, thereby mediating the flow of water between glial cells and the cavities filled with CSF and the intravascular space.

• Publication year

  1997

• Venue

  Journal of Neuroscience

• Publication date

  1997-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.17-01-00171.1997PMID 8987746PMCID PMC6793699
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Neuronal and glial handling of glutamate and glutamine during hypoosmotic stress: a biochemical and quantitative immunocytochemical analysis using the rat cerebellum as a model.

  1996cited by this paper
• Pathophysiology of the aquaporin water channels.

  1996cited by this paper
• Organization of AMPA Receptor Subunits at a Glutamate Synapse: A Quantitative Immunogold Analysis of Hair Cell Synapses in the Rat Organ of Corti

  1996cited by this paper
• The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.

  1996cited by this paper
• Aquaporin-1 water channel protein in lung: ontogeny, steroid-induced expression, and distribution in rat.

  1996cited by this paper
• The aquaporin family of water channels in kidney: an update on physiology and pathophysiology of aquaporin-2.

  1996cited by this paper
• Distribution of aquaporin-4 water channel expression within rat kidney.

  1995cited by this paper
• Molecular Cloning and Characterization of an Aquaporin cDNA from Salivary, Lacrimal, and Respiratory Tissues (*)

  1995cited by this paper
• Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.

  1995influential reference
• The aquaporin family of water channels in kidney.

  1995influential reference
• Aquaporin-3 water channel localization and regulation in rat kidney.

  1995cited by this paper
• Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations

  1995cited by this paper
• Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane.

  1995influential reference
• Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues.

  1995influential reference
• Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry.

  1995influential reference
• Expression of VAMP-2-like protein in kidney collecting duct intracellular vesicles. Colocalization with Aquaporin-2 water channels.

  1995influential reference
• The aquaporin family of molecular water channels.

  1994cited by this paper
• Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues.

  1994influential reference
• Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance.

  1994influential reference
• CHIP28 water channels are localized in constitutively water-permeable segments of the nephron

  1993influential reference
• Aquaporin CHIP: the archetypal molecular water channel.

  1993cited by this paper
• Mechanosensitive channels transduce osmosensitivity in supraoptic neurons

  1993cited by this paper
• Neuronal-glial exchange of taurine during hypo-osmotic stress: a combined immunocytochemical and biochemical analysis in rat cerebellar cortex.

  1993cited by this paper
• Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia.

  1993influential reference
• Metabolic compartmentation of glutamate and glutamine: morphological evidence obtained by quantitative immunocytochemistry in rat cerebellum.

  1992cited by this paper
• Appearance of Water Channels in Xenopus Oocytes Expressing Red Cell CHIP28 Protein

  1992cited by this paper
• Freeze-substitution and Lowicryl HM20 embedding of fixed rat brain: suitability for immunogold ultrastructural localization of neural antigens.

  1991cited by this paper
• Role of glial cells in the regulation of the brain ion microenvironment

  1989influential reference
• Regulation of vasopressin secretion.

  1989cited by this paper
• Role of glial cells in the regulation of the brain ion microenvironment.

  1989influential reference
• 3 Regulation of vasopressin secretion

  1989cited by this paper
• High potassium conductance in astrocyte endfeet.

  1986influential reference
• Control of extracellular potassium levels by retinal glial cell K+ siphoning.

  1984cited by this paper
• Regional specialization of retinal glial cell membrane

  1984cited by this paper
• Immunocytochemical, Golgi and electron microscopic characterization of putative dendrites in the ventral glial lamina of the rat supraoptic nucleus.

  1982cited by this paper
• Golgi-like immunoperoxidase staining of hypothalamic magnocellular neurons that contain vasopressin, oxytocin or neurophysin in the rat.

  1981cited by this paper
• Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia.

  1966cited by this paper

• Glymphatic system dysfunction: a link between sleep disorders and neurodegeneration.

  2026cites this paper
• The rise of astrocytes: are they guardians or troublemakers of the brain disorder?

  2026cites this paper
• The spatial architecture of neuroimmune interactions in epilepsy.

  2026cites this paper
• Aquaporin-4 Dysfunction in Depression: From Pathogenic Mechanisms to Novel Therapeutic Targeting

  2026cites this paper
• Water exchange across the blood-CSF barrier: A systematic review.

  2026cites this paper
• Role of astrocytes connexins - pannexins in acute brain injury

  2025cites this paper
• Early neuromyelitis optica antibody-induced molecular changes in aquaporin 4 and associated proteins at astrocyte endfeet in murine brain tissues.

  2025cites this paper
• Extracellular vesicles as precision therapeutics for psychiatric conditions: targeting interactions among neuronal, glial, and immune networks

  2025cites this paper
• Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human

  2025cites this paper
• Development of perivascular astrocyte processes

  2025cites this paper
• Association of MRI parameters of brain waste clearance function with cortisol and inflammatory markers in middle-aged and older adults with major depressive disorder.

  2025cites this paper
• Neutrophils-astrocyte interactions in central nervous system inflammation

  2025cites this paper
• A systematic study of the distribution and expression of aquaporin water channels in normal adult human brain

  2025cites this paper
• New perspectives on the glymphatic system and the relationship between glymphatic system and neurodegenerative diseases.

  2025cites this paper
• Interoceptive Signaling by Circulating Insulin Like Growth Factor I and Neuroprotection by Exercise.

  2025cites this paper
• Understanding the intricacies of cellular mechanisms in remyelination: The role of circadian rhythm.

  2025cites this paper
• Ferroptosis: is it both cause and effect in refractory epilepsy?

  2025cites this paper
• Brain fluid physiology in ischaemic stroke; more than just oedema

  2025cites this paper
• Immune-mediated blood-brain barrier disruption after ischemic stroke: mechanisms and therapeutic targets

  2025cites this paper
• Oxidative Stress, Metabolic Impairment and Neuroinflammation are Associated With Target Organ Damage in SHRSP

  2025cites this paper
• In vivo imaging of the barrier properties of the glia limitans during health and neuroinflammation

  2025cites this paper
• Agomelatine Targets Aquaporin-4 Polarization to Rescue Glymphatic Dysfunction in Parkinson's Disease.

  2025cites this paper
• The review of nasal drug delivery system: The strategies to enhance the efficiency of intranasal drug delivery by improving drug absorption.

  2025cites this paper
• Barriers in the Nervous System: Challenges and Opportunities for Novel Biomarkers in Amyotrophic Lateral Sclerosis

  2025cites this paper
• Biomarkers of blood–brain barrier and neurovascular unit integrity in human cognitive impairment and dementia

  2025cites this paper
• Blood‐Brain Barrier Dysfunction in Adults With Heart Failure

  2025cites this paper
• Long-term nucleus basalis cholinergic lesions alter the structure of cortical vasculature, astrocytic density and microglial activity in Wistar rats.

  2025cites this paper
• The Impact of Aquaporin‐4 Deletion on K+‐Induced Astrocytic Swelling Depends on K+ Concentration

  2025cites this paper
• The integrity of perivascular spaces is absolutely essential for proper function of the glymphatic system waste and excess water removal from the brain.

  2025cites this paper
• Research hotspots and frontiers of glymphatic system and Alzheimer’s disease: a bibliometrics analysis

  2025cites this paper
• Inhibiting EPAC1 improves brain edema and neurological outcomes by regulating AQP4 polarization after intracerebral hemorrhage.

  2025cites this paper
• Shared mechanisms in neuromyelitis optica spectrum disorder and spaceflight-associated neuro-ocular syndrome: Insights into central nervous system fluid dynamics, glymphatic function, and astrocyte dysregulation.

  2025cites this paper
• The Role of Choroid Plexus in Hydrocephalus from the Perspective of Structure and Function: a Therapeutic Target

  2025cites this paper
• The deletion of AQP4 and TRPV4 affects astrocyte swelling/volume recovery in response to ischemia-mimicking pathologies

  2024cites this paper
• Aryl hydrocarbon receptor impairs circadian regulation in Alzheimer's disease: Potential impact on glymphatic system dysfunction

  2024cites this paper
• Navigating Human Astrocyte Differentiation: Direct and Rapid one-step Differentiation of Induced Pluripotent Stem Cells to Functional Astrocytes Supporting Neuronal Network development

  2024cites this paper
• Enhancing glymphatic fluid transport by pan-adrenergic inhibition suppresses epileptogenesis in male mice

  2024cites this paper
• Transport of β-amyloid from brain to eye causes retinal degeneration in Alzheimer’s disease

  2024cites this paper
• Structural and molecular characterization of astrocyte and vasculature connectivity in the mouse hippocampus and cortex

  2024cites this paper
• Liquiritin ameliorates painful diabetic neuropathy in SD rats by inhibiting NLRP3-MMP-9-mediated reversal of aquaporin-4 polarity in the glymphatic system

  2024cites this paper
• Analysis of solid-state NMR data facilitated by MagRO_NMRViewJ with Graph_Robot: Application for membrane protein and amyloid.

  2024cites this paper
• Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways

  2024cites this paper
• The Blood-Brain Barrier: Composition, Properties, and Roles in Brain Health.

  2024cites this paper
• Role of aquaporin-4 polarization in extracellular solute clearance

  2024cites this paper
• In vivo mapping of cellular resolution neuropathology in brain ischemia with diffusion MRI

  2024cites this paper
• Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder

  2024cites this paper
• The Aquaporin‐4 Expression and Localization in the Olfactory Epithelium Modulate the Odorant‐Evoked Responses and Olfactory‐Driven Behavior

  2024cites this paper
• Astrocyte regulation of extracellular space parameters across the sleep-wake cycle

  2024cites this paper
• Role of the Glymphatic System in Alzheimer’s Disease and Treatment Approaches: A Narrative Review

  2024cites this paper
• Aquaporin‐4 deletion leads to reduced infarct volume and increased peri‐infarct astrocyte reactivity in a mouse model of cortical stroke

  2024cites this paper
• Blood–brain barrier alterations and their impact on Parkinson’s disease pathogenesis and therapy

  2024cites this paper
• Aquaporin‐4 activation facilitates glymphatic system function and hematoma clearance post‐intracerebral hemorrhage

  2024cites this paper
• Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection

  2024cites this paper
• Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF‐κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus

  2024cites this paper
• Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury

  2024cites this paper
• Astrocytes adopt a progenitor-like migratory strategy for regeneration in adult brain

  2024cites this paper
• Aquaporin-4 as an early cerebrospinal fluid biomarker of Alzheimer's disease

  2024cites this paper
• GABAergic system and chloride cotransporters as potential therapeutic targets to mitigate cell death in ischemia

  2024cites this paper
• Relapse-Independent disease activity in neuromyelitis optica spectrum disorder: A systematic review.

  2024cites this paper
• The Pseudotumor Cerebri Syndrome.

  2024cites this paper
• Addressing neurodegeneration in glaucoma: Mechanisms, challenges, and treatments.

  2024cites this paper
• Molecular Basis of Neuronal and Microglial States in the Aging Brain and Impact on Cerebral Blood Vessels

  2024cites this paper
• Ginkgolide B can alleviate spinal glymphatic system dysfunction and provide neuroprotection in PDN rats by inhibiting matrix metalloproteinase-9.

  2024cites this paper
• A Comparative Review of Typical and Atypical Optic Neuritis: Advancements in Treatments, Diagnostics, and Prognosis

  2024cites this paper
• Toward New AQP4 Inhibitors: ORI-TRN-002

  2024cites this paper
• Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ

  2024cites this paper
• Aquaporin-4 as a cerebrospinal fluid biomarker of Alzheimer’s disease

  2024cites this paper
• The Involvement of Glial Cells in Blood–Brain Barrier Damage in Neuroimmune Diseases

  2024cites this paper
• Astrocytes and Tinnitus

  2024cites this paper
• Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

  2024cites this paper
• A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

  2024cites this paper
• A rare case of systemic lupus erythematosus‐associated neuromyelitis optica spectrum disorder with cystic lesions and dual seropositivity for anti‐AQP4 and anti‐MOG antibodies

  2024cites this paper
• Effect of heat stress on the hypothalamic expression profile of water homeostasis‐associated genes in low‐ and high‐water efficient chicken lines

  2024cites this paper
• Aquaporine-4 inhibition attenuates Pentylentetrazole-induced behavioral seizures and cognitive impairments in kindled rats.

  2024cites this paper
• Microglia at the blood brain barrier in health and disease

  2024cites this paper
• AQP4 Endocytosis-Lysosome Degradation Mediated by MMP-9/β-DG Involved in Diabetes Cognitive Impairment

  2024cites this paper
• Spatiotemporal molecular dynamics of the developing human thalamus

  2023cites this paper
• In vivo Mapping of Cellular Resolution Neuropathology in Brain Ischemia by Diffusion MRI

  2023cites this paper
• Astrocyte metabolism and signaling pathways in the CNS

  2023cites this paper
• The aquaporin-4 water channel and updates on its potential as a drug target for Alzheimer’s disease

  2023cites this paper
• Assessing the Role of Aquaporin 4 in Skeletal Muscle Function

  2023cites this paper
• Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

  2023cites this paper
• Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system

  2023cites this paper
• Autoimmune-mediated astrocytopathy

  2023influential citation
• Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus"

  2023cites this paper
• Relationship between circulating mitochondrial DNA and microRNA in patients with major depression.

  2023cites this paper
• Importance of Water Transport in Mammalian Female Reproductive Tract

  2023cites this paper
• Choroid Plexus Aquaporins in CSF Homeostasis and the Glymphatic System: Their Relevance for Alzheimer’s Disease

  2023cites this paper
• Aquaporin-1 and Aquaporin-4 Expression in Ependyma, Choroid Plexus and Surrounding Transition Zones in the Human Brain

  2023influential citation
• T cell deletional tolerance restricts AQP4 but not MOG CNS autoimmunity

  2023cites this paper
• From Homeostasis to Pathology: Decoding the Multifaceted Impact of Aquaporins in the Central Nervous System

  2023cites this paper
• Impaired glymphatic flow as a potential driver of pain chronification.

  2023cites this paper
• Idiopathic intracranial hypertension in patients with cerebral small vessel disease: A case report

  2023cites this paper
• Stroke-induced damage on the blood–brain barrier

  2023cites this paper
• Glymphatic system: an emerging therapeutic approach for neurological disorders

  2023cites this paper
• The Brain’s Glymphatic System: Drawing New Perspectives in Neuroscience

  2023cites this paper
• The Role of Aquaporins in Spinal Cord Injury

  2023cites this paper
• Prolonged Light Exposure Induces Circadian Impairment in Aquaporin-4-Knockout Mice

  2023cites this paper
• The link between SARS-CoV-2 related microglial reactivity and astrocyte pathology in the inferior olivary nucleus

  2023cites this paper
• Brain-Targeting Emodin Mitigates Ischemic Stroke via Inhibiting AQP4-Mediated Swelling and Neuroinflammation

  2023cites this paper