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Cell-specific expression of APP and GABABR1 isoforms in wild-type and the APP NL-G-F mouse model of Alzheimer's disease.

Amyloid precursor protein (APP) is a type I transmembrane protein that undergoes proteolytic processing to generate amyloid-β, the main comp … ined relative RNA levels of R1a and R1b isoforms in oligodendrocytes, microglia, endothelial cells, astrocytes, and neurons in adult mice using two approaches. We developed an isoform-specific RNAseq analysis workflow to probe publicly available datasets. We also isolated these cell types from a single mouse brain and performed RT-qPCR with isoform-specific …

Betulinic Acid Promotes Motor Function Recovery After Spinal Cord Injury by Inhibiting Apoptosis Through Myc/NF-κB Signaling Pathway.

Spinal cord injury (SCI) imposes a remarkable burden on affected cases and their families, while current treatment options remain insufficie … target genes. In vitro, lipopolysaccharide was used to induce a secondary SCI condition in cultured astrocytes, enabling the evaluation of BA's effects on inflammatory and apoptotic responses. The results demonstrated that BA could significantly promote motor function recovery and reduce the expression levels of inflammation-related cytokines, including IL-1 …

Trifluoro-icaritin attenuates neuropathic pain-associated anxiety-like behaviors and hippocampal oxidative stress in rats.

Neuropathic pain is frequently accompanied by anxiety-like symptoms. Trifluoro-icaritin (ICTF), an icaritin derivative with reported central … and complementary experiments were performed in H2O2-treated HT22 cells and LPS-stimulated primary astrocytes. ICTF (5 mg/kg, i.p.) attenuated mechanical allodynia and improved several anxiety-related behavioral measures in SNI rats, together with reduced hippocampal malondialdehyde, increased superoxide dismutase activity, and improved neuronal morphology. …

Neuroinflammation in glaucoma: a myriad of cellular pathways and players.

Glaucoma is a complex neurodegenerative disease with multiple subtypes, yet all are characterized by the progressive dysfunction and loss of … uroinflammation is broadly defined here as immune-relevant responses, often involving microglia and astrocytes, within the central nervous system which may include peripheral immune cell infiltration. Burgeoning evidence has implicated glia in the development and progression of glaucoma in human tissues and mouse models. Most mouse models of glaucoma to date …

2-Mercaptoethanol enhances the yield of exosomes showing therapeutic potency in alleviating spinal cord injury mice.

BACKGROUND: Limited passage numbers of mesenchymal stem cells (MSCs) present challenges in producing sufficient exosomes for spinal cord injury (SCI) treatment. OBJECTIVES: This study investigates whether β-mercaptoethanol (BME) preconditioning of MSCs can increase exosome yield for SCI therapy. METHODS: Exosomal content was analyzed using silver staining and SYBR Gold staining. Cell viability was assessed via CCK-8 and EdU assays. IL-1β, IL-6, TNF-α, and MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Neuronal differentiation influenced by astrocytes was evaluated t…

Optimizing the structure of repurposed metformin can improve anti-cholinesterase and anti-amyloidogenic effects.

Alzheimer's disease (AD) and diabetes mellitus (DM) share common pathological features, including insulin resistance, oxidative stress, and … cence assay in vitro, and antioxidative properties in human umbilical endothelial cells (HUVEC) and astrocytes. In vitro assays revealed that studied derivatives exhibit selective inhibitory activity against BChE over AChE. Additionally, certain derivatives demonstrated a synergistic effect with donepezil in AChE inhibition. The derivatives effectively inhib …

CHI3L1: An Emerging Player in Neuroinflammation and Neurodegeneration.

Neuroinflammation is now being identified as the major factor in the development of various neurological disorders. It is a vital process in neurons and the brain that maintains homeostasis under normal and healthy conditions. However, in hyperactivated states, neuroinflammation can also go awry when microglia and astrocytes enter a toxic, reactive state that can release chemicals that damage neurons. When innate immune cells encounter pathogens, infection, cell debris, or misfolded proteins, they release certain chemokines and cytokines to eliminate the intruding particles and protect the bra…

Glial Alterations in the Glutamatergic and GABAergic Signalling Pathways in a Mouse Model of Lafora Disease, a Severe Form of Progressive Myoclonus Epilepsy.

AIMS: Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy characterised by the accumulation of insoluble deposits of glycogen in the brain and peripheral tissues. In mouse models of LD, we have identified neuroinflammation as a secondary hallmark of the disease, characterised by increased levels of reactive astrocytes and activated microglia. Our previous work demonstrated that the TNF and IL-6 inflammatory signalling pathways are the primary drivers of this neuroinflammatory phenotype. In this work, we aimed to investigate whether TNF and IL-6 pathway activation …

MILD TRAUMATIC BRAIN INJURY IMPAIRS EPISODIC MEMORY IN RATS.

Mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury. Symptoms following mTBI fall into physical, emotional, … a marker of activated microglia/macrophages and glial fibrillary acidic protein (GFAP), a marker of astrocytes. Concussion injury was associated with time-dependent morphological changes in astrocytes and microglia in injured rats compared to sham rats. This study is the first to document episodic memory impairment in an animal model of mTBI.

OCT4 and Nestin Expression in the Microenvironment of Primary Central Nervous System Lymphomas.

Background: Angiogenesis is essential for the survival of neoplasms. Our aim was to describe the clinical profile of primary central nervous … an 58.16 years). Three patients (12 %) had immunosuppression. Nestin staining revealed hypertrophic astrocytes forming patches about blood vessels with positive cytoplasmic staining in endothelium and pericytes (5-10% of the intra-tumor arterioles). These findings were seen in both B and T lymphomas. OCT4 nuclear expression was only observed in five large B- …

Anatomy, histology and ultrastructure of the adult human olfactory peduncle: Blood vessel and corpora amylacea assessment.

The mammalian olfactory system is responsible for processing environmental chemical stimuli and comprises several structures, including the … r pyramidal cells, the latter associated with projection neurons of the anterior olfactory nucleus. Astrocytes were uniformly distributed with a more radial morphology in the EL. Oligodendrocytes were mainly located in the AL. Blood vessels (BVs) were evenly distributed along the OP, with a mean luminal area of 82.9 µm² and a density of 1.26 %, with a signif …

Метаболический перепрограммирование глиальных клеток: пути жирной кислоты в качестве регулятора ремиэлизации в множестве склероза.

Множественный склероз (MS) — аутоиммунное расстройство, характеризующееся нейроинфламмацией и постепенным демиэлированием, приводящим к необратимым нейронным повреждениям и инвалидности. Несмотря на то, что текущее иммунодуляторное лечение медленно развивается, они не могут эффективно стимулировать регенерацию миелина. В недавних исследованиях подчеркивалась критическая роль глиевых клеток - микроглии, астроцитов и олигодендроцитов - в ремонте миелина, при этом метаболизм жирной кислоты (FA) становится центральным регулятором этого процесса. Жирные кислоты необходимы не только для поддержания

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an autoimmune disorder characterized by neuroinflammation and progressive demyelination, resulting in irreversibl … ote myelin regeneration. Recent research has emphasized the critical role of glial cells-microglia, astrocytes, and oligodendrocytes-in myelin repair, with fatty acid (FA) metabolism emerging as a central regulator of this process. Fatty acids are essential not only for maintaining myelin structure but also for the metabolic reprogramming of glial cells duri …

The benefits of high-intensity physical exercise before and after Parkinson's disease induction in rats.

High-intensity physical activity is a non-pharmacological intervention that has been tested as a treatment for Parkinson's disease (PD). The objective of the study was to investigate the benefits of high-intensity physical exercise on the number of neurons and astrocytes in a a rat model of Parkinson's disease submitted to training before and after the inducing injury. Seventy Wistar rats were used, distributed as follows: nine rats trained before PD induction (DP-Exa), nine trained after PD induction (DP-Exd), 10 trained before and after PD induction (DP-Exad), and nine sedentary rats (DP-Sed…

Astrogliosis in the GFAP-CreERT2:Rosa26iDTR Mouse Model Does Not Exacerbate Retinal Microglia Activation or Müller Cell Gliosis under Hypoxic Conditions.

Diabetic retinopathy (DR) affects over 140 million people globally. The mechanisms that lead to blindness are still enigmatic but there is evidence that sustained inflammation and hypoxia contribute to vascular damage. Despite efforts to understand the role of inflammation and microglia in DR's pathology, the contribution of astrocytes to hypoxic responses is less clear. To investigate the role of astrocytes in hypoxia-induced retinopathy, we utilized a 7-day systemic hypoxia model using the GFAP-CreERT2:Rosa26iDTR transgenic mouse line. This allows for the induction of inflammatory reactive a…

Glial alterations in the glutamatergic and GABAergic signaling pathways in a mouse model of Lafora disease, a severe form of progressive myoclonus epilepsy.

Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy characterized by the accumulation of insoluble deposits of aberrant glycogen (polyglucosans), named Lafora bodies (LBs), in the brain but also in peripheral tissues. It is assumed that the accumulation of LBs is related to the appearance of the characteristic pathological features of the disease. In mouse models of LD, we and others have reported an increase in the levels of reactive astrocytes and activated microglia, which triggers the expression of the different pro-inflammatory mediators. Recently, we have de…

EGCG-NPs inhibition HO-1-mediated reprogram iron metabolism against ferroptosis after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH), a devastating disease with a high mortality rate and poor outcomes, tightly associated with the dysregulation … CG inhibited oxyhemoglobin (OxyHb)-induced the over-expression of HO-1, which mainly distributed in astrocytes and microglial cells. Subsequently, EGCG blocked ferrous iron accumulation through HO-1-mediated iron metabolic reprogramming. Therefore, oxidative stress and mitochondrial dysfunction was rescued by EGCG, which resulted in the downregulation of fer …

Intracisternal AAV9-MAG-hABCD1 Vector Reverses Motor Deficits in Adult Adrenomyeloneuropathy Mice.

Worldwide, thousands of male patients who carry ATP Binding Cassette Subfamily D Member 1 (ABCD1) mutations develop adrenomyeloneuropathy (A … ression at 24 months of age was present in 22% (18-27) of oligodendrocytes (OLs) and 22% (17-26) of astrocytes and not detected in neurons or microglia. Abundant hABCD1 expression was also observed in OLs and astrocytes in the cerebellum and brainstem and, to a lesser level, in the lower spinal cord, not in the dorsal root ganglia or brain cortex. In conclus …

Inhibition of Neuromyelitis Optica Immunoglobulin G Binding to Aquaporin-4 by the Small Molecule Blocker Melanthioidine.

BACKGROUND: Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease affecting the optic nerves and spinal cord. The binding of neuromyelitis optica immunoglobulin G (NMO- IgG) and aquaporin-4 (AQP4) on the surface of astrocytes in the serum and cerebrospinal fluid is the main pathogenesis of NMO. Currently, therapeutic strategies for NMO include a reduction of the secondary inflammation response and the number of NMO-IgG, which can only alleviate clinical symptoms rather than fundamentally preventing a series of pathological processes caused by NMO-IgG binding to A…

The Mlc1 Promoter Directs Müller Cell-specific Gene Expression in the Retina.

PURPOSE: Because the importance of glia in regulating brain functions has been demonstrated, genetic technologies that manipulate glial cell … , a marker of Müller cells, but not with the cell markers for blood vessels, microglia, neurons, or astrocytes. CONCLUSIONS: The Mlc1 promoter allows us to manipulate gene expression in Müller cells without affecting astrocytes in the retina. TRANSLATIONAL RELEVANCE: Gene manipulation under control of Mlc1 promoter offers novel technique to investigate the …

Emerging Role of miR-21-5p in Neuron-Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with neuron-glia dysfunction and dysregulated miRNAs. We previously repo … , but not in non-AD MCI individuals, supports its discriminatory potential. Microglia, neurons, and astrocytes differentiated from the same induced pluripotent stem cells from PSEN1ΔE9 AD patients all showed miR-21 elevation. In AD neurons, miR-124/miR-21 overexpression was recapitulated in their exosomes. In AD microglia, the upregulation of iNOS and miR-21 …