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N. Aladdin and S. A. Ghareib, "Vitamin D3 Exerts a Neuroprotective Effect in Metabolic Syndrome Rats: Role of BDNF/TRKB/Akt/GS3Kβ Pathway," Journal of Biochemical and Molecular Toxicology 38, no. 12 (2024): e70082, https://doi.org/10.1002/jbt.70082. The above article, published online on 09 December 2024 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Hari K. Bhat; and Wiley Periodicals, LLC. The retraction has been agreed upon following concerns raised by a third party regarding data reuse between this article and two other articles previously published elsewhere by the same authors. An investigation confirmed that there are substantial overlaps among the three papers. The authors provided some supporting data and explained that the three studies were related, and that data from a limited number of animals were shared to confirm the disease model. However, analysis of the data showed that the overlaps were not restricted to disease model validation. The editors have therefore lost confidence in the results presented in this article and consider the conclusions to be invalid. The authors disagree with the retraction. Show less

Press needle therapy, may alleviate depressive-like behaviors. Male rats were randomly allocated into four groups ( Press-needle ameliorated depressive-like behaviors in CUMS-exposed rats, restored body weight gain and improved behavioral performance. The treatment upregulated the hippocampal BDNF/TrkB/CREB signaling pathway, increasing BDNF, TrkB, CREB, AKT, and PI3K in the hippocampus. The therapy modulated serotonergic neurotransmission by increasing hippocampal 5-HTT expression, while downregulating 5-HT1A and 5-HT2C receptors and PKA. Notably, press-needle exerted anti-neuroinflammatory effects, reducing hippocampal and serum levels of TNF-α and IL-6. Histopathological analysis confirmed its neuroprotective efficacy, demonstrating attenuated neuronal damage in hippocampal tissues. Show less

The accumulation of CAG nucleotide duplicates in the huntingtin (HTT) gene triggers a neurological ailment described as Huntington's disease (HD), which is an irreversible, progressive, and inherited condition and affects both motor and cognitive abilities, resulting in a range of symptoms, including irregular gestures (chorea, dyskinesia), psychological disorders, and advanced dementia. Agomelatine is a novel antidepressant and melatonin analog. It exerts a synergistic pharmacological mechanism, combining stimulation of both MT1/MT2 melatonergic receptors with inhibition of 5-HT2C receptors. It was evaluated for its potential neuroprotective impact against HD triggered by 3-nitropropionic acid (3-NP) in rats. Four groups were established using a total of 40 rats: Group I (CTRL), Group II (AGO), Group III (3-NP), and Group IV (AGO + 3-NP). Deficits in motor function provoked by 3-NP were alleviated by agomelatine, as evidenced by increased ambulation and rearing frequencies, alongside a notable decline in immobility time of the open field assessment, elevated final falloff time of the rotarod assessment, and improved grip strength. Agomelatine also improved synaptic plasticity and neuronal survival by optimizing the expression and activity of the BDNF/TrKB/PI3K/AKT pathway and inhibiting apoptosis, microglial, and astrocytic activation. Furthermore, agomelatine administration reduced the expression of ROCK1, suppressing the release of inflammatory responses. Finally, agomelatine possessed neuroprotective activity, as proved by enhancing motor activity and histopathological abnormalities via improving the BDNF/TrKB/PI3K/AKT survival cascade and suppressing the ROCK1 inflammatory pathway. Show less

Sciatic nerve injury represents a prevalent and incapacitating condition characterized by denervation, muscular atrophy, and compromised functionality. The Protein Kinase B (PKB)/ Akt signaling cascade serves as a vital modulator of skeletal muscle hypertrophy, metabolic processes, and regenerative capabilities. Subsequent to sciatic nerve injury, the PI3K/Akt signaling pathway exhibits dysregulation, exacerbating muscle atrophy and hindering recovery processes due to feedback inhibition of PKB/Akt phosphorylation by mTORC1, which consequently increases the expression of E3 ubiquitin ligases and causes muscle atrophy. Additionally, a multitude of other variables, encompassing neurotrophic factors, intracellular calcium ion concentrations, carboxyl-terminal modulator proteins, connexins, and tumor necrosis factor-α, either exert regulatory influences on Akt or are subject to regulation by Akt in a multifaceted manner. Hence, this review discusses the complex role of the PI3K/Akt signaling pathway in skeletal muscle dynamics following sciatic nerve injury, emphasizing its regulatory mechanisms and downstream effectors, and highlights strategies to target this pathway to enhance muscle regeneration and restore functional capabilities. Show less

Although chemotherapy remains a life-saving intervention for numerous cancer patients, it is often accompanied by depressive symptoms and cognitive impairments, "chemobrain." Noteworthy, multiple studies emphasize the role of glycogen synthase kinase 3β (GSK-3β) in depression and chemobrain; nevertheless, no available data relate GSK-3β inhibitors to chemobrain. Herein, this study aims to investigate the effect of the GSK-3β inhibitor, lithium, on behavioral and neurobiological abnormalities in a doxorubicin (DOX)-induced rat model of chemobrain. The chemobrain model was established through weekly intraperitoneal injections of doxorubicin (2 mg/kg/wk) for a duration of 4 weeks, whereas lithium (100 mg/kg/d, i.p.) was administered concomitantly over the same period. Behavioral, neurochemical, and histopathological evaluations were performed after the experimental protocol. DOX-induced depressive-like behaviors and cognitive impairments, with reduction in prefrontal cortex tropomyosin receptor kinase B receptors, brain-derived neurotrophic factor protein kinase B (BDNF), and phosphorylated protein kinase B, elevating the levels of the active form of GSK-3β, which lessened phosphorylated mammalian target of rapamycin/nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 and BDNF/synapsin-1 pathways, while triggering overexpression of NF-κB, proinflammatory cytokines, oxidative stress, apoptosis, tau hyperphosphorylation, and neurodegeneration. Lithium ameliorated DOX-induced behavioral, neurochemical, and histological abnormalities. To the best of our knowledge, this study presents the first evidence that lithium treatment can modulate DOX-induced depression and cognitive deficits, potentially through revamping the BDNF/tropomyosin-related kinase receptor B/protein kinase B/GSK-3β/mammalian target of rapamycin/nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 signaling cascade, thereby attenuating oxidative stress, neuroinflammation, apoptosis, neurofibrillary tangles, and subsequent neurodegeneration. SIGNIFICANCE STATEMENT: To the best of our knowledge, this study is the first to detect antidepressant and procognitive effects of lithium in DOX-induced chemobrain via GSK-3β inhibition. Accordingly, lithium offers a promising therapeutic target for the management of chemotherapy-induced depression and chemobrain. Show less