Intranasal Insulin Alleviates Traumatic Brain Injury by Inhibiting Autophagy and Endoplasmic Reticulum Stress‐mediated Apoptosis Through the PI3K/Akt/mTOR Signaling Pathway

Ding, Xin; Zhang, Lili; Zhang, Xiaopeng; Qin, Y.; Kang, Yu; Yang, Xiaokun

doi:10.1016/j.neuroscience.2023.08.009

Cited by 8 publications

(3 citation statements)

References 54 publications

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“…One of these pathways, the PI3K/AKT/mTOR pathway, is known to play a crucial role (Mezhlumyan et al, 2022 ; Raab-Graham et al, 2006 ). Activating the PI3K/AKT/mTOR signaling could suppress neural inflammation, autophagy, and apoptosis, then increase synaptic protein synthesis after TBI (Ding et al, 2023 ; Jan et al, 2016 ). Furthermore, this pathway is also involved in the resolving of depression symptoms by regulating the function of the synapses and promoting synaptogenesis (Dwyer & Duman, 2013 ; Fakhri et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury

Huang,

Zhu,

et al. 2024

Neuromol Med

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Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients’ serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD’s protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway.

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Section: Introductionmentioning

confidence: 99%

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury

Huang,

Zhu,

et al. 2024

Neuromol Med

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“…7 The insulin/insulin receptor/PI3-kinase/Akt signaling was also found inhibition of hypoxic-ischemic-induced apoptosis through inhibiting autophagy and endoplasmic reticulum stress. 8 Therefore, insulin is usually used to preserve the vitality of renal tubular epithelial cells in culture. 9 In rats with diabetes mellitus (DM), insulin treatment before ischemia-reperfusion injury (IRI) preserved both renal function and histomorphology, whereas insulin treatment after IRI had no such protective effects.…”

Section: Introductionmentioning

confidence: 99%

“… 7 The insulin/insulin receptor/PI3-kinase/Akt signaling was also found inhibition of hypoxic-ischemic-induced apoptosis through inhibiting autophagy and endoplasmic reticulum stress. 8 …”

Section: Introductionmentioning

confidence: 99%

Short–Term Preconditioning with Insulin and Glucose Efficiently Protected the Kidney Against Ischemia-Reperfusion Injury via the P-AKT-Bax-Caspase-3 Signaling Pathway in Mice

Sun,

Bing,

Zhang

et al. 2024

DDDT

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The bioenergetics of traumatic brain injury and its long-term impact for brain plasticity and function

Thapak,

Gomez-Pinilla

2024

Pharmacological Research

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Intranasal Insulin Alleviates Traumatic Brain Injury by Inhibiting Autophagy and Endoplasmic Reticulum Stress‐mediated Apoptosis Through the PI3K/Akt/mTOR Signaling Pathway

Cited by 8 publications

References 54 publications

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury

Short–Term Preconditioning with Insulin and Glucose Efficiently Protected the Kidney Against Ischemia-Reperfusion Injury via the P-AKT-Bax-Caspase-3 Signaling Pathway in Mice

The bioenergetics of traumatic brain injury and its long-term impact for brain plasticity and function

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