DL‐3‐<i>n</i>‐butylphthalide alleviates vascular cognitive impairment by regulating endoplasmic reticulum stress and the Shh/Ptch1 signaling‐pathway in rats

Niu, Xiaoli; Jiang, Xin; Xu, Guodong; Zheng, Guimin; Tang, Zhipeng; Yin, Nan; Li, Xiuqin; Yang, Yanyan; Lv, Peiyuan

doi:10.1002/jcp.27332

Cited by 51 publications

(22 citation statements)

References 41 publications

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“…In fact, in a neuronal model of VD low concentrations of copper potentiate zinc-induced ER stress pathways 68 . Moreover, DL-3-n-butylphthalide was www.nature.com/scientificreports/ shown to protect against cognitive deficits in a rat model of VD by regulating ER stress-related markers 69 . This work highlights a new conceptual model for AD and PD pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Differential protein expression in diverse brain areas of Parkinson’s and Alzheimer’s disease patients

Esteves

Cardoso

2020

Sci Rep

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Many hypotheses have been postulated to define the etiology of sporadic Parkinson's and Alzheimer's disorders (PD and AD) but there is no consensus on what causes these devastating age-related diseases. Braak staging of both pathologies helped researchers to better understand the progression and to identify their prodromal and symptomatic phases. Indeed, it is well accepted that Lewy body pathology and neurofibrillary tangles appearance correlates with disease progression and severity of symptoms in PD and AD, respectively. Additionally, several studies in PD and AD models try to disclose which cellular mechanisms are defaulted and trigger the neurodegenerative process that culminates with neuronal death causing PD and AD classical symptomatology. Herein, we determined expression levels of proteins involved in microtubule assembly, autophagic-lysosomal pathway and unfolded protein response in the cortex, hippocampus and SNpc of PD and AD patients, vascular dementia patients and aged-match controls. The differential expression allowed us to determine which pathways are determinant to synaptic dysfunction and to establish a time line for disease progression. Our results allow us to challenge the hypothesis that both PD and AD pathologies are caused by α-synuclein or Aβ pathology propagation throughout the brain in a prion-like manner.

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Section: Discussionmentioning

confidence: 99%

Differential protein expression in diverse brain areas of Parkinson’s and Alzheimer’s disease patients

Esteves

Cardoso

2020

Sci Rep

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“…Further, it shows neuroprotective effects in AD (Wang et al, 2016), PD (Xiong et al, 2012), neurotoxicity (Zhao et al, 2016), traumatic brain injury (Zhao et al, 2017), and spinal cord injury (He et al, 2017). NBP is protective against cognitive impairment induced by CCH by increasing sonic hedgehog/patched 1 pathway markers and decreasing endoplasmic reticulum stress-related markers (Niu et al, 2018), or activating the AKT/Nrf2 pathway in the hippocampus of rats (Qi et al, 2018). Our previous work has revealed that NBP can quickly accelerate a recovery in CBF and improvements in cognitive function (Xiong et al, 2017; Li et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Dl-3-n-Butylphthalide Reduces Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion Through GDNF/GFRα1/Ret Signaling Preventing Hippocampal Neuron Apoptosis

Wei

Lin

et al. 2019

Front. Cell. Neurosci.

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Hippocampal neuron death is a key factor in vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH). Dl-3-n-butylphthalide (NBP) is a multiple-effects drug. Therefore, the potential molecular mechanisms underlying CCH and its feasible treatment should be investigated. This study had two main purposes: first, to identify a potential biomarker in a rat model of CCH induced VD using antibody microarrays; and second, to explore the neuroprotective role of NBP at targeting the potential biomarker. Glial cell line-derived neurotrophic factor (GDNF)/GDNF family receptor alpha-1 (GFRα1)/receptor tyrosine kinase (Ret) signaling is altered in the hippocampus of CCH rats; however, NBP treatment improved cognitive function, protected against hippocampal neuron apoptosis via regulation of GDNF/GFRα1/Ret, and activated the phosphorylation AKT (p-AKT) and ERK1/2 (p-ERK1/2) signaling. We also found that 1 h oxygen-glucose deprivation (OGD) followed by 48 h reperfusion (R) in cultured hippocampal neurons led to downregulation of GDNF/GFRα1/Ret. NBP upregulated the signaling and increased neuronal survival. Ret inhibitor (NVP-AST487) inhibits Ret and downstream effectors, including p-AKT and p-ERK1/2. Additionally, both GDNF and GFRα1 expression are markedly inhibited in hippocampal neurons by coincubation with NVP-AST487, particularly under conditions of OGD/R. GDNF/GFRα1/Ret signaling and neuronal viability can be maintained by NBP, which activates p-AKT and p-ERK1/2, increases expression of Bcl-2, and decreases expression of Bax and cleaved caspase-3. The current study showed that GDNF/GFRα1/Ret signaling plays an essential role in the CCH induced VD. NBP was protective against hippocampal neuron apoptosis, and this was associated with regulation of GDNF/GFRα1/Ret and AKT/ERK1/2 signaling pathways, thus reducing cognitive impairment.

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“…Studies have demonstrated that NBP exerts multi‐target protective effects against ischemic stroke, including reducing oxidative stress, inhibiting inflammatory responses, alleviating neuronal apoptosis, ameliorating BBB damage, and increasing regional blood flow . Moreover, emerging evidence indicates that NBP also have beneficial effects on cognitive function of Alzheimer's Disease (AD) and vascular dementia, through regulating endoplasmic stress, reducing neuronal apoptosis, and glial reactivity …”

Section: Introductionmentioning

confidence: 99%

dl‐3‐n‐butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion

Han

Zhang

et al. 2019

CNS Neurosci Ther

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Aims Effects of dl‐3‐n‐butylphthalide (NBP) on white matter damage and cognitive impairment in vascular cognitive impairment (VCI) have not been well studied. This study aimed to investigate the effects of NBP treatment on chronic cerebral hypoperfusion‐induced white matter lesions and cognitive dysfunction in mice. Methods Mice were subjected to bilateral common carotid artery stenosis (BCAS) for over 30 days. The cerebral blood flow was detected using a laser Doppler flowmetry. Cognitive functions were assessed by several behavioral tests. We also evaluated the effects of NBP on the blood‐brain barrier (BBB) disruption and reactive astrogliosis, using Evans Blue extravasation, Western blot, CBA, and immunofluorescence in BCAS mice and cultured astrocytes. Results The results indicated that NBP treatment attenuated spatial memory dysfunction while promoted cerebral perfusion and white matter integrity in BCAS mice. Moreover, NBP treatment prevented BBB leakage and damage of endothelial cells, as well as disruption of endothelial tight junctions. Furthermore, NBP administration effectively decreased the number of activated astrocytes and pro‐inflammatory cytokines, as well as the production of MMPs, in BCAS‐induced mice and LPS‐stimulated astrocytes. Conclusion Our results indicated that NBP represents a promising therapy for chronic cerebral hypoperfusion‐induced white matter damage and cognitive impairment.

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DL‐3‐n‐butylphthalide alleviates vascular cognitive impairment by regulating endoplasmic reticulum stress and the Shh/Ptch1 signaling‐pathway in rats

Cited by 51 publications

References 41 publications

Differential protein expression in diverse brain areas of Parkinson’s and Alzheimer’s disease patients

Differential protein expression in diverse brain areas of Parkinson’s and Alzheimer’s disease patients

Dl-3-n-Butylphthalide Reduces Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion Through GDNF/GFRα1/Ret Signaling Preventing Hippocampal Neuron Apoptosis

dl‐3‐n‐butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion

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