DL0410 ameliorates cognitive disorder in SAMP8 mice by promoting mitochondrial dynamics and the NMDAR-CREB-BDNF pathway

Lian, Wenwen; Wei, Zhou; Zhang, Bao-yue; Jia, Hao; Xu, Lvjie; Liu, Ailin; Du, Guanhua

doi:10.1038/s41401-020-00506-2

Cited by 33 publications

(13 citation statements)

References 61 publications

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“…Learning and memory deficits are the main clinical symptoms of dementia. Previous reports have found that various animal models of dementia, including SAMP8 mice, exhibit cognitive and behavioral impairments characterized by impaired learning and memory [22][23][24]. In this study, 7month-old SAMP8 mice showed a significant decrease in the percentage of spontaneous alternations in the Y maze test and an increase in escape latency and a decrease in the percentage of time spent in the target quadrant in the MWM test, consistent with previous reports.…”

Section: Discussionsupporting

confidence: 92%

Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice

Hou

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Learning and memory disorders and decreased neuroplasticity are the main clinical manifestations of age-induced cognitive dysfunction. Orexin A (OxA) has been reported to show abnormally elevated expression in the cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD) and to be associated with cognitive impairment. Here, we further assessed whether the excitatory neurotransmitter OxA is involved in neuroplasticity and cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice. In this study, we investigated the mechanism of OxA by using behavioral tests, CSF microdialysis, immunofluorescence, toluidine blue staining, gene silencing, transmission electron microscopy, and Western blotting. The results showed that 10 Hz electroacupuncture (EA) effectively alleviated learning and memory impairment in 7-month-old SAMP8 mice, reduced OxA levels in the CSF, increased the level of the neurotransmitter glutamate, alleviated pathological damage to hippocampal tissue, improved the synaptic structure, enhanced synaptic transmission, and regulated the expression of cAMP/PKA/CREB signaling pathway-related proteins. These results suggest that EA enhances neuroplasticity in SAMP8 mice by regulating the OxA-mediated cAMP/PKA/CREB signaling pathway, thus improving cognitive function. These findings suggest that EA may be beneficial for the prevention and treatment of age-induced cognitive impairment.

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Section: Discussionsupporting

confidence: 92%

Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice

Hou

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The gene of neurotrophin BDNF is regulated by nuclear Ca 2+ -CREB signaling (Favaron et al, 1993;Hardingham and Bading, 2010). NMDAR activation increases the release of BDNF, which protects neurons from damage caused by NMDAR blockade (Fabbrin et al, 2020;Lian et al, 2021). Some studies have shown that improving mitochondrial dynamics and increasing the activity of the NMDAR-CREB-BDNF pathway could ameliorate synaptic function and neuronal survival in SAMP8 mice (Lian et al, 2021).…”

Section: Nmdar-dependent Neuroprotection In Epilepsymentioning

confidence: 99%

“…NMDAR activation increases the release of BDNF, which protects neurons from damage caused by NMDAR blockade (Fabbrin et al, 2020;Lian et al, 2021). Some studies have shown that improving mitochondrial dynamics and increasing the activity of the NMDAR-CREB-BDNF pathway could ameliorate synaptic function and neuronal survival in SAMP8 mice (Lian et al, 2021). Synaptic NMDARs and extrasynaptic NMDARs have different physiological functions.…”

Section: Nmdar-dependent Neuroprotection In Epilepsymentioning

confidence: 99%

Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

Chen

Liu

et al. 2022

Front. Mol. Neurosci.

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Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.

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Section: Potential Mechanisms Underlying Thementioning

confidence: 99%

“…Xu et al [ 30 ] found that inhibition of the mammalian target of rapamycin (mTOR)/nuclear factor kappa-B (NF- κ B) signaling pathway in a mouse model of diabetic encephalopathy resulted in improved cognitive performance and elevated levels of SYN to regulate synaptic plasticity. Activation of the N-methyl- d -aspartate receptor (NMDAR)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) pathway was also shown to promote SYN expression and improve memory impairment in senescence-accelerated mouse prone 8 (SAMP8) mice [ 31 ]. Similarly, BDNF overexpression in 5× familial AD (5-FAD) mice promoted the recovery of SYN and postsynaptic density protein-95 (PSD-95) as well as the number of presynaptic vesicles at excitatory synapses, enhanced long-term potentiation (LTP), and thus improved memory impairment [ 32 ].…”

Section: Potential Mechanisms Underlying the Effects Of Acupuncture O...mentioning

confidence: 99%

Acupuncture Interventions for Alzheimer’s Disease and Vascular Cognitive Disorders: A Review of Mechanisms

Yang

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cognitive impairment (CI) related to Alzheimer’s disease (AD) and vascular cognitive disorders (VCDs) has become a key problem worldwide. Importantly, CI is a neuropsychiatric abnormality mainly characterized by learning and memory impairments. The hippocampus is an important brain region controlling learning and memory. Recent studies have highlighted the effects of acupuncture on memory deficits in AD and VCDs. By reviewing the literature published on this topic in the past five years, the present study intends to summarize the effects of acupuncture on memory impairment in AD and VCDs. Focusing on hippocampal synaptic plasticity, we reviewed the mechanisms underlying the effects of acupuncture on memory impairments through regulation of synaptic proteins, AD characteristic proteins, intestinal microbiota, neuroinflammation, microRNA expression, orexin system, energy metabolism, etc., suggesting that hippocampal synaptic plasticity may be the common as well as the core link underlying the above mechanisms. We also discussed the potential strategies to improve the effect of acupuncture. Additionally, the effects of acupuncture on synaptic plasticity through the regulation of vascular–glia–neuron unit were further discussed.

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DL0410 ameliorates cognitive disorder in SAMP8 mice by promoting mitochondrial dynamics and the NMDAR-CREB-BDNF pathway

Cited by 33 publications

References 61 publications

Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice

Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice

Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

Acupuncture Interventions for Alzheimer’s Disease and Vascular Cognitive Disorders: A Review of Mechanisms

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