Extracellular Matrix Regulation in Physiology and in Brain Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7049 - 7049

Published: April 11, 2023

The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that ECM plays important roles during development, healthy adult brain diseases. aim of this review is to briefly discuss physiological its contribution pathogenesis disease, highlighting gene expression changes, transcriptional factors involved, a role for microglia regulation. Much research conducted thus far on disease states has focused “omic” approaches reveal differences related ECM. Here, we recent findings alterations ECM-associated genes seizure, neuropathic pain, cerebellar ataxia, age-related neurodegenerative disorders. Next, evidence implicating transcription factor hypoxia-inducible 1 (HIF-1) regulating genes. HIF-1 induced response hypoxia, also targets involved remodeling, suggesting hypoxia could contribute remodeling conditions. We conclude by discussing play regulation perineuronal nets (PNNs), specialized form central nervous system. show can modulate PNNs diseased states. Altogether, these suggest altered highlight remodeling.

Language: Английский

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Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?

Biology, Journal Year: 2023, Volume and Issue: 12(8), P. 1139 - 1139

Published: Aug. 17, 2023

Traumatic brain injury (TBI) is one of the leading causes long-lasting morbidity and mortality worldwide, being a devastating condition related to impairment nervous system after an external traumatic event resulting in transitory or permanent functional disability, with significant burden healthcare system. Harmful events underlying TBI can be classified into two sequential stages, primary secondary, which are both associated breakdown tissue homeostasis due blood–brain barrier, osmotic imbalance, inflammatory processes, oxidative stress, excitotoxicity, apoptotic cell death, ultimately loss functionality. The present study provides updated review concerning roles edema, inflammation, stress on changes from TBI. proper characterization phenomena contribute improvement care, rehabilitation quality life affected people.

Language: Английский

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Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(8), P. 1475 - 1488

Published: July 17, 2024

Abstract Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show terminals interneurons localize to holes in adult mouse somatosensory cortex. Approximately 95% contain and astrocytic processes expressing Kir4.1, glutamate GABA transporters. Hence, tripartite synapses. In brain, PNN degradation causes an expanded coverage neuronal somata without altering axon terminals. The loss impairs transmitter potassium uptake, resulting spillage into extrasynaptic space. Our data astrocytes cooperate synaptically released signals physiological conditions. Their combined action is altered models Alzheimer’s disease epilepsy where disrupted.

Language: Английский

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Mechanisms of astrocyte aging in reactivity and disease

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 21, 2025

Normal aging alters brain functions and phenotypes. However, it is not well understood how astrocytes are impacted by aging, nor they contribute to neuronal dysfunction disease risk as organisms age. Here, we examine the transcriptional, cell biology, functional differences in across normal aging. Astrocytes at baseline heterogenous, responsive their environments, critical regulators of microenvironments function. With increasing age, adopt different immune-related senescence-associated states, which relate organelle loss homeostasis maintenance, both autonomously non-cell autonomously. These perturbed states increasingly associated with age-related onset neurodegeneration, suggesting that astrocyte a compelling target for future manipulation prevention disease.

Language: Английский

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Differential impacts of germline and adult aggrecan knockout in PV+ neurons on perineuronal nets and PV+ neuronal function

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Perineuronal nets (PNNs) are a condensed form of extracellular matrix primarily found around parvalbumin-expressing (PV+) interneurons. The postnatal maturation PV+ neurons is accompanied with the formation PNNs and reduced plasticity. Alterations in PNN neuron function have been described for mental disorders such as schizophrenia autism. highly dependent on aggrecan, proteoglycan encoded by ACAN gene, but it remains unknown if produced themselves. Thus, we established knockout (KO) mouse model (ACANflx/PVcre) an adeno-associated virus to specifically eliminate aggrecan production from neurons, germline or adult animals, respectively. KO eliminated expression labeled Wisteria floribunda agglutinin (WFA), most commonly used marker. Surprisingly, electrophysiological properties interneurons ocular dominance plasticity ACANflx/PVcre mice were similar controls. In contrast, AAV-mediated increased Moreover, vivo Chondroitinase ABC treatment resulted firing rate cells frequency spontaneous excitatory postsynaptic currents (sEPSC), phenotype associated chABC WT animals. These findings suggest that compensatory mechanisms may be activated during development response loss aggrecan. Indeed, qPCR bulk tissue indicates other components, including neurocan tenascin-R, expressed at higher levels Finally, behavioral testing revealed had long-term memory controls Morris water maze. However, they employed bolder search strategies spatial learning showed lower level anxiety-related behavior open field zero

Language: Английский

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Neuroanatomy of spinal nociception and pain in dogs and cats: a practical review for the veterinary clinician

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 20, 2025

Chronic pain is a prevalent condition in companion animals and poses significant welfare challenges. To address these concerns effectively, veterinary clinicians must have comprehensive understanding of the neuroanatomy nociception intricate processes underlying perception. This knowledge essential for planning implementing targeted treatment strategies. However, much existing information on mechanisms derived from studies rodents or humans, highlighting need further translational research to bridge this gap applications. review aims provide with an in-depth overview spinal nociceptive pathways dog cat, tracing journey nociceptor activation cortical processing brain. Additionally, explores factors influencing signaling By enhancing fundamental physiological processes, work seeks lay groundwork developing effective therapies manage complexities chronic animals.

Language: Английский

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Astrocytes in functional recovery following central nervous system injuries

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 602(13), P. 3069 - 3096

Published: Sept. 13, 2023

Astrocytes are increasingly recognised as partaking in complex homeostatic mechanisms critical for regulating neuronal plasticity following central nervous system (CNS) insults. Ischaemic stroke and traumatic brain injury associated with high rates of disability mortality. Depending on the context type injury, reactive astrocytes respond diverse morphological, proliferative functional changes collectively known astrogliosis, which results both pathogenic protective effects. There is a large body research negative consequences astrogliosis injuries. also growing interest how might some contexts be help to limit spread injury. However, little about contribute chronic recovery phase ischaemic In this review, we explore functions various aspects secondary such oedema, inflammation blood-brain barrier dysfunction. We discuss current knowledge astrocyte contribution tissue regeneration, including angiogenesis, neurogenesis, synaptogenesis, dendrogenesis axogenesis. Finally, astrocyte-related factors that, if selectively targeted, could form basis astrocyte-targeted therapeutic strategies better address currently untreatable CNS disorders.

Language: Английский

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Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7435 - 7435

Published: April 18, 2023

The extracellular matrix (ECM) of the brain is a dynamic structure made up vast network bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these due to genetic variation or environmental stressors are thought affect functions may result disease. However, most mechanistic studies date usually focus on aspects diseases pay less attention relevance processes governing nature disease pathogenesis. Thus, ECM's diversified biological roles, increasing interest its involvement disease, lack sufficient compiled evidence regarding relationship with Parkinson's (PD) pathology, we aimed compile existing boost current knowledge area provide refined guidance for future research. Here, this review, gathered postmortem tissue induced pluripotent stem cell (iPSC)-related from PubMed Google Scholar identify, summarize describe common macromolecular alterations expression ECM components (PD). A literature search was conducted until 10 February 2023. overall hits database manual proteomic transcriptome were 1243 1041 articles, respectively. Following full-text articles 24 transcriptomic found be eligible inclusion. According studies, proteins such as collagens, fibronectin, annexins, tenascins recognized differentially expressed Transcriptomic displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, adhesion molecules limited number relevant accessed our search, indicating much work remains carried out better understand roles neurodegeneration believe review will elicit focused primary thus support ongoing efforts discovery development diagnostic biomarkers well therapeutic agents

Language: Английский

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Adolescent intermittent ethanol exposure decreases perineuronal nets in the hippocampus in a sex dependent manner: Modulation through pharmacological inhibition of RPTPβ/ζ

Neuropharmacology, Journal Year: 2024, Volume and Issue: 247, P. 109850 - 109850

Published: Jan. 29, 2024

Adolescence is a critical period for brain maturation in which this organ undergoes plasticity mechanisms that increase its vulnerability to the effects of alcohol. Significantly, ethanol-induced disruption hippocampal neurogenesis has been related cognitive decline adulthood. During adolescence, perineuronal nets (PNNs), extracellular matrix structures highly affected by ethanol consumption, plays fundamental role and hippocampus. Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ anchor point PNNs on cell surface. Using adolescent intermittent access (IAE) model, we previously showed MY10, small-molecule inhibitor RPTPβ/ζ, reduces chronic consumption male mice but not females prevents IAE-induced neurogenic loss We have now tested if these MY10 are sex-dependent modulatory actions PNNs. Our findings suggest complex interplay between alcohol exposure, neural structures, sex-related differences modulation parvalbumin (PV)-positive cells In general, IAE increased number PV + female hippocampus reduced intensity different regions, particularly mice. Notably, found pharmacological inhibition RPTPβ/ζ with regulates alterations intensity, correlates protection from neurotoxic may be capacity gene expression key components

Language: Английский

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The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102092 - 102092

Published: Oct. 13, 2023

Language: Английский

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