Escitalopram alleviates stress-induced Alzheimer's disease-like tau pathologies and cognitive deficits by reducing hypothalamic-pituitary-adrenal axis reactivity and insulin/GSK-3β signal pathway activity

Wu, Chao; Gong, Wei-Gang; Wang, Yanjuan; Sun, Junjun; Zhou, Hong; Zhang, Zhijun; Ren, Qiangqiang

doi:10.1016/j.neurobiolaging.2018.03.011

Cited by 19 publications

(15 citation statements)

References 47 publications

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“…In accordance with our previous results in CUMS rats ( Wu et al, 2018b ), in the present study, we also found that both stress susceptible and resilient mice showed impaired cognitive function, which suggest that chronic stress-induced cognitive impairment is not caused by chronic stress-induced emotional impairment. Interestingly, we found that tau accumulation was found in both CUSD and CUSR mice.…”

Section: Discussionsupporting

confidence: 93%

“…Our results suggested that NBP could both decrease phosphorylated and nonphosphorylated tau accumulation in the hippocampus of stressed mice. As the accumulated tau is hyperphosphorylated at some of the GSK-3 favorite sites during CUMS stimulation ( Ning et al, 2018 ; Wu et al, 2018b ), we studied the involvement of GSK-3. The level of serine-9-phosphorylated GSK-3β (inactive form) was decreased after CUMS in mice, which could be reversed by NBP treatment.…”

Section: Resultsmentioning

confidence: 99%

“…After a survival period of 10 weeks, the mice were subject to 8 weeks of CUMS as described in detail previously by us and Lotan A et al ( Wu et al, 2018a ; Lotan et al, 2018 ). The CUMS included seven different stressors, including deprivation of food and water (12 h), empty cage (12 h), tilted cage (14 h), nip-tail (1 min), light-dark cycle reversal, cold environment (5 min), and restraint in a bottle (1 h).…”

Section: Methodsmentioning

confidence: 99%

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Dl-3-n-Butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation

Chen¹,

He²,

Liu³

et al. 2022

Neurobiology of Stress

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Dl-3-n-Butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation

Chen¹,

He²,

Liu³

et al. 2022

Neurobiology of Stress

Self Cite

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“…Evidence supporting the idea that GSK3 inhibitors may have an additional potential for alleviating NPS originates from several studies in animals showing that GSK3 inhibition may contribute to the action of antidepressants 13–17 and antipsychotics 18–23 . This idea is additionally substantiated by studies with selective GSK3 inhibitors, which showed that these drugs produce antidepressant-like effects in animal models 24–27 .…”

Section: Introductionmentioning

confidence: 99%

The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer’s disease in rodents

Griebel

Stemmelin

Lopez-Grancha

et al. 2019

Sci Rep

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Glycogen synthase kinase 3 (GSK3) has been identified as a promising target for the treatment of Alzheimer’s disease (AD), where abnormal activation of this enzyme has been associated with hyperphosphorylation of tau proteins. This study describes the effects of the selective GSK3 inhibitor, SAR502250, in models of neuroprotection and neuropsychiatric symptoms (NPS) associated with AD. In P301L human tau transgenic mice, SAR502250 attenuated tau hyperphosphorylation in the cortex and spinal cord. SAR502250 prevented the increase in neuronal cell death in rat embryonic hippocampal neurons following application of the neurotoxic peptide, Aβ25–35. In behavioral studies, SAR502250 improved the cognitive deficit in aged transgenic APP(SW)/Tau(VLW) mice or in adult mice after infusion of Aβ25–35. It attenuated aggression in the mouse defense test battery and improved depressive-like state of mice in the chronic mild stress procedure after 4 weeks of treatment. Moreover, SAR502250 decreased hyperactivity produced by psychostimulants. In contrast, the drug failed to modify anxiety-related behaviors or sensorimotor gating deficit. This profile confirms the neuroprotective effects of GSK3 inhibitors and suggests an additional potential in the treatment of some NPS associated with AD.

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“…The inhibition of JNK phosphorylation can decrease the level of phospho-tau proteins. AD-like tau pathology and cognitive impairment are exacerbated by reducing insulin/GSK-3β signaling activity [75]. Tau hyperphosphorylation and the CaM-CaMKIV signal pathway participate in the recovery of memory ability in AD-like rats [76].…”

Section: The Transplanted Stem Cells Regulate the Production And Removal Of Aberrant Proteinsmentioning

confidence: 99%

Novel Balance Mechanism Participates in Stem Cell Therapy to Alleviate Neuropathology and Cognitive Impairment in Animal Models with Alzheimer’s Disease

Qin

Wang

2021

Cells

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Stem cell therapy improves memory loss and cognitive deficits in animal models with Alzheimer’s disease. The underlying mechanism remains to be determined, but it may involve the interaction of stem cells with hippocampal cells. The transplantation of stem cells alters the pathological state and establishes a novel balance based on multiple signaling pathways. The new balance mechanism is regulated by various autocrine and paracrine cytokines, including signal molecules that target (a) cell growth and death. Stem cell treatment stimulates neurogenesis and inhibits apoptosis, which is regulated by the crosstalk between apoptosis and autophagy—(b) Aβ and tau pathology. Aberrant Aβ plaques and neurofibrillary tau tangles are mitigated subsequent to stem cell intervention—(c) inflammation. Neuroinflammation in the lesion is relieved, which may be related to the microglial M1/M2 polarization—(d) immunoregulation. The transplanted stem cells modulate immune cells and shape the pathophysiological roles of immune-related genes such as TREM2, CR1, and CD33—(e) synaptogenesis. The functional reconstruction of synaptic connections can be promoted by stem cell therapy through multi-level signaling, such as autophagy, microglial activity, and remyelination. The regulation of new balance mechanism provides perspective and challenge for the treatment of Alzheimer’s disease.

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Escitalopram alleviates stress-induced Alzheimer's disease-like tau pathologies and cognitive deficits by reducing hypothalamic-pituitary-adrenal axis reactivity and insulin/GSK-3β signal pathway activity

Cited by 19 publications

References 47 publications

Dl-3-n-Butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation

Dl-3-n-Butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation

The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer’s disease in rodents

Novel Balance Mechanism Participates in Stem Cell Therapy to Alleviate Neuropathology and Cognitive Impairment in Animal Models with Alzheimer’s Disease

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