Pharmacological activation of Sig-1R ameliorates pathological neuroinflammation in rats with diabetic neuropathic pain via the Akt/GSK-3β/NF-κB pathway

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and characterized by spontaneous neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as target for analgesic development. It anti-inflammatory properties found to regulate DNP. However, it not known whether Sig-1R can ameliorate pathological neuroinflammation in present study used rat model DNP highly selective agonist assess the effects protein on rats with type 2 mellitus. were divided into Control, Model, PRE-084 (0.3 mg/kg), (0.6 (1 metformin (Met, 20 mg/kg) groups, seven per group, their body weight, fasting blood glucose, mechanical withdrawal threshold (MWT) thermal latency (TWL) tested weekly two weeks. After treatment PRE-084, thresholds significantly improved, together changes dorsal root ganglion, reductions serum levels TNF-α, IL-1β, IL-6, MOD, prostaglandin E2, activity superoxide dismutase was increased. mRNA cyclooxygenase reduced. Pharmacological inhibition BD1047 (10 µM) abolished Sig-1R-mediated activation lipopolysaccharide-treated BV-2 microglial cells. also that increased phosphorylation serine/threonine kinase B (Akt) glycogen synthase 3β (GSK3β) at Ser9, inhibiting nuclear factor kappa B(NF-κB)-mediated thus reducing findings suggest effect may be reduce level inflammation downregulating Akt/GSK-3β/NF-κB signaling, thereby contributing disease.

Language: Английский

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Revealing the molecular links between coronary heart disease and cognitive impairment: the role of aging-related genes and therapeutic potential of stellate ganglion block

Biogerontology, Journal Year: 2024, Volume and Issue: 26(1)

Published: Nov. 28, 2024

Coronary heart disease (CHD) and cognitive impairment frequently co-occur in aging populations, yet the molecular mechanisms linking these conditions remain unclear. This study aims to elucidate roles of key aging-related genes (ARGs), specifically FKBP5 DDIT3, pathophysiology CHD impairment, evaluate therapeutic potential stellate ganglion block (SGB). Using single-cell RNA sequencing (scRNA-seq) bulk (bulk RNA-seq) data, we identified DDIT3 as pivotal upregulated both conditions. Experimental findings show that SGB effectively modulates ARG-related pathways through autonomic regulation, suppressing estrogen NF-κB signaling pathways, thereby reducing expression pro-inflammatory cytokines such SRC, MMP2, FKBP5, IRAK1, MYD88, while upregulating vasodilation-related gene NOS3. modulation improved endothelial cardiac function enhanced cerebral blood flow (CBF), leading improvement. Behavioral assessments, including novel object recognition (NOR) Morris water maze (MWM) tests, demonstrated SGB-treated rats outperformed untreated MI rats, with significant recovery over time. Further support from laser Doppler flowmetry (LDF) electroencephalogram (EEG) analyses revealed increased left frontal stabilized neural activity, indicating a favorable neurophysiological environment for rehabilitation. Our suggest (LSGB) provides benefits targeted modulation, establishing its addressing intersecting pathologies impairment.

Language: Английский

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Inhibition of PGAM5 hyperactivation reduces neuronal apoptosis in PC12 cells and experimental vascular dementia rats

Archives of Gerontology and Geriatrics, Journal Year: 2024, Volume and Issue: 131, P. 105732 - 105732

Published: Dec. 25, 2024

Language: Английский

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Öğrenme ve Bellek Deneylerinde Deney Hayvanlarına Yaklaşım ve Deney Modellerinin Değerlendirilmesi

Harran Üniversitesi Tıp Fakültesi Dergisi, Journal Year: 2024, Volume and Issue: unknown, P. 547 - 556

Published: Oct. 21, 2024

Öğrenme ve bellek, canlıların yeni bilgiler edinip depolanmasını gerektiğinde geri çağrılmasını sağlayan yaşamlarını sağlıklı bir şekilde devam ettirebilmeleri için gerekli olan süreçlerdir. bellek ile ilgili beynimizin ana bölümleri amigdala, hipokampus, beyincik prefron-tal kortekstir. Bu alanlardaki bozulmalar öğrenme mekanizmalarını etkilemektedir. Hayvan çalışmaları insanlarda bozukluklarının patofizyolojisi hakkında önemli sunarak tedavi farmakolojik ajanların keşfedilmesine katkıda bulunur. Ancak hayvan çalışmalarına başlamadan önce yapılacak çalışmanın amacını bu amaca ulaşabilmek çalışmada hangi tür deney hayvanının kullanılacağını hayvanında test modelin uygun olduğunu belirlemek, seçilen türünde geçerliliği güvenilirliği bilgi sahibi olmak oldukça önem arz eder. amaçla derlemede, hayvanla-rında yaygın olarak kullanılan modelleri testleriyle temel bilgilerin sunulması testler arasında kıyaslama yapma imkanının amaçlanmıştır.

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