Long-term social isolation inhibits autophagy activation, induces postsynaptic dysfunctions and impairs spatial memory

Wang, Bin; Wu, Qiong; Lei, Lei; Sun, Hai-Lun; Ntim, Michael; Zhang, Xuan; Wang, Ying; Zhang, Yue; Ge, Bi-Ying; Wu, Xing; Wang, Yue; Yi, Xin; Zhao, Jie; Li, Shao

doi:10.1016/j.expneurol.2018.09.009

Cited by 47 publications

(39 citation statements)

References 73 publications

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“…In vivo microdialysis was carried out according to our previous report [29]. Microdialysis enables direct assessment of interstitial fluid (ISF) Aβ in the setting of intact, complex neural networks [9].…”

Section: Microdialysis and Elisamentioning

confidence: 99%

Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice

Jiang

Wang

et al. 2020

Alz Res Therapy

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Background: Amyloid beta (Aβ) which is recognized as a main feature of Alzheimer's disease (AD) has been proposed to "spread" through anatomically and functionally connected brain regions. The entorhinal cortex and perforant path are the earliest affected brain regions in AD. The perforant path is the most vulnerable circuit in the cortex with respect to both aging and AD. Previous data show that the origins and terminations of the perforant path are susceptible to amyloid deposition at the younger age in AD. Nogo receptor (NgR) plays an essential role in limiting injury-induced axonal growth and experience-dependent plasticity in the adult brain. It has been suggested that NgR is involved in AD pathological features, but the results have been conflicting and the detailed mechanism needs further investigation. In this study, the effect of NgR in the perforant path on the pathological and functional phenotype of APP/PS1 transgenic mice was studied. Methods: To genetically manipulate NgR expression, adeno-associated virus (AAV) with short hairpin (shRNA) against NgR was injected into the perforant path of APP/PS1 transgenic mice, followed by an assessment of behavioral, synaptic plasticity and neuropathological phenotypes. NgR was overexpressed or knockdown in neuroblastoma N2a cells and APPswe/HEK293 cells to investigate the interaction between NgR and amyloid precursor protein (APP).

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Section: Microdialysis and Elisamentioning

confidence: 99%

Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice

Jiang

Wang

et al. 2020

Alz Res Therapy

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“…Oxidative stress can induce apoptosis [20], and the apoptosis may result in the loss of postsynaptic proteins [21]. Postsynaptic current was modulated by postsynaptic proteins [22] while postsynaptic neurons modulate learning [23] and their dysfunction will impair memory [24]. Thus, oxidative stress can impair learning and memory by affecting postsynaptic activity.…”

Section: Introductionmentioning

confidence: 99%

Tetrahydroxystilbene Glucoside Ameliorates Infrasound-Induced Central Nervous System (CNS) Injury by Improving Antioxidant and Anti-Inflammatory Capacity

Zhou

Yang

Fan

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Infrasound is a major threat to global health by causing injuries of the central nervous system (CNS). However, there remains no effective therapeutic agent for preventing infrasound-caused CNS injury. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glycoside (THSG) exerts protective function against CNS injuries and may have beneficial effects on infrasound-induced CNS impairment. Methods. A mouse model with CNS (oxidative stress-induced inflammation and neuronal apoptosis) injuries was established when the mouse was exposed to the infrasound of 16 Hz at 130 dB for 2 h each day and the duration of treatment was 8 d. The mice were divided into the control (CG, healthy mice), the model (MG, model mice), and the THSG (EG, experimental group, model mice treated with THSG) groups. The learning and memory impairments caused by infrasound were examined using a Morris water maze test. Lipid profiles, antioxidant biomarkers, and inflammatory cytokines in hippocampus tissue were measured by using corresponding ELISA kits. Meanwhile, BCL-2/BAX/caspase-3 signaling pathway was measured in the hippocampi and prefrontal cortex of the mouse brain using real-time qPCR and Western blot. Nissl’s stain was used to measure neuronal necrosis in the hippocampi and prefrontal cortex of the mouse brain. Results. THSG significantly ameliorated the learning and memory impairments caused by infrasound. On the other hand, THSG improved lipid profiles, increased antioxidant properties by affecting the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA), and displayed anti-inflammatory action via the downregulation of IL- (interleukin-) 6, IL-8, IL-10, TNF- (tumor necrosis factor-) α, and hs-CRP (high-sensitivity C-reactive protein) in the hippocampal tissues of the mouse model (P<0.05). Additionally, Nissl’s stain showed that THSG inhibited infrasound-induced neuronal necrosis in the hippocampi and prefrontal cortex. Besides, THSG exerted antiapoptosis function by upregulating the level of Bcl-2 and downregulating the levels of BAX and caspase-3 in the hippocampi. Conclusion. THSG may be an effective anti-infrasound drug against CNS injury by improving antioxidant, anti-inflammatory, antiapoptosis, and antinecrosis capacities. Further research is still needed to confirm the exact molecular mechanism.

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“…Rapamycin, which is an autophagy inducer (Wang et al, 2019 ), was administered 1 h before KA administration to simulate xenon-induced autophagy enhancement. We found that rapamycin treatment increased autophagy levels, which was indicated by decreased SQSTM1 and increased LC3-II levels ( Figures 7A–E ).…”

Section: Resultsmentioning

confidence: 99%

Xenon Exerts Neuroprotective Effects on Kainic Acid-Induced Acute Generalized Seizures in Rats via Increased Autophagy

Zhu

Zhao³

et al. 2020

Front. Cell. Neurosci.

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Xenon has been shown to have neuroprotective effects and is clinically used as a favorable safe inhalation anesthetic. We previously confirmed the neuroprotective effects of xenon treatment in epileptic animals. However, the mechanism underlying these protective effects remains unclear. We aimed to assess the effects of xenon inhalation on autophagy in neuronal injury induced by acute generalized seizures. Kainic acid (KA) was injected into the lateral ventricle of male Sprague–Dawley rats to induce acute generalized seizures. Next, the rats were treated via inhalation of a 70% xenon/21% oxygen/9% nitrogen mixture for 60 min immediately after KA administration. The control group was treated via inhalation of a 79% nitrogen/21% oxygen mixture. Subsequently, two inhibitors (3-methyladenine or bafilomycin A 1 ) or an autophagy inducer (rapamycin) were administered, respectively, before KA and xenon administration to determine the role of autophagy in the protective effects of xenon. The levels of apoptosis, neuronal injury, and autophagy were determined in all the rats. Xenon inhalation significantly attenuated the severity of the seizure-induced neuronal injury. Increased autophagy accompanied this inhibitive effect. Autophagy inhibition eliminated these xenon neuroprotective effects. A simulation of autophagy using rapamycin recapitulated xenon’s protective effects on KA-induced acute generalized seizures in the rats. These findings confirmed that xenon exerts strong neuroprotective effects in KA-induced acute generalized seizures. Further, they indicate that increased autophagy may underlie the protective effects of xenon. Therefore, xenon and autophagy inducers may be useful clinical options for their neuroprotective effects in epileptic seizures.

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Long-term social isolation inhibits autophagy activation, induces postsynaptic dysfunctions and impairs spatial memory

Cited by 47 publications

References 73 publications

Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice

Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice

Tetrahydroxystilbene Glucoside Ameliorates Infrasound-Induced Central Nervous System (CNS) Injury by Improving Antioxidant and Anti-Inflammatory Capacity

Xenon Exerts Neuroprotective Effects on Kainic Acid-Induced Acute Generalized Seizures in Rats via Increased Autophagy

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