scholarly journals Neuropeptide S Ameliorates Cognitive Impairment of APP/PS1 Transgenic Mice by Promoting Synaptic Plasticity and Reducing Aβ Deposition

2019 ◽  
Vol 13 ◽  
Author(s):  
Peng Zhao ◽  
Xiaohang Qian ◽  
Yunjuan Nie ◽  
Na Sun ◽  
Zhongxuan Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Neuropeptide S

scholarly journals Suan-Zao-Ren Decoction Ameliorate Synaptic Plasticity Through the Inhibition of JAK2/STAT3 Signaling Pathway in APP/PS1 Transgenic Mice

2020 ◽  
Author(s):  
Qing-Hua Long ◽  
Yong-Gui Wu ◽  
Li-Ling He ◽  
Li Ding ◽  
Ai-Hua Tan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Nissl Staining ◽  
Stat3 Pathway ◽  
Plaque Deposition ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α ◽  
Neurological Illnesses

Abstract Background: Suan-Zao-Ren Decoction (SZRD) has been widely used to treat neurological illnesses, like dementia, insomnia, and depression. However, mechanisms underlying SZRD’s improvement in cognitive function remains unclear. In this study, we examined SZRD’s effect on APP/PS1 transgenic mice as well as mechanisms associated with SZRD’s action in alleviating neuroinflammation and improving the synaptic plasticity. Methods: The APP/PS1 mice were treated with different dosages of SZRD (12.96 and 25.92 g/kg/d, in L-SZRD and H-SZRD groups, respectively) for four weeks. Morris water maze was conducted to determine changes in behaviors of the mice after the treatment. Meanwhile, in the samples of the hippocampus, Nissl staining and Golgi-Cox staining were used to detect the synaptic plasticity, Western blot (WB) was employed to test expressions of Aβ1-42, APP, ADAM10, BACE1, PS1, IDE, IBA1, GFAP, PSD95 and SYN, as well as the expressions of JAK2, STAT3 and their phosphorylation patterns to detect involvement of JAK2/STAT3 pathway. Besides, we examined the serum contents of IL-1β, IL-6, and TNF-α using ELISA.Results: Compared to the APP/PS1 mice without any treatment, SZRD, especially the L-SZRD, significantly ameliorated cognitive impairment of the APP/PS1 mice with decreases in the loss of neurons and Aβ plaque deposition as well as improvement of synaptic plasticity in the hippocampus (all P<0.05). Also, SZRD, in particular, the L-SZRD markedly inhibited the serum IL-6, IL-1β, and TNF-α, while reducing the expression of p-JAK2-Tyr1007 and p-STAT3-Tyr705 in the hippocampus of the APP/PS1 mice (all P<0.05). Conclusion: The SZRD, especially the L-SZRD, may improve the cognitive impairment and ameliorate the neural degeneration in APP/PS1 transgenic mice through decreasing Aβ accumulation and inhibiting neuroinflammation via JAK2/STAT3 pathway.

scholarly journals Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qing-Hua Long ◽  
Yong-Gui Wu ◽  
Li-Ling He ◽  
Li Ding ◽  
Ai-Hua Tan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Nissl Staining ◽  
Stat3 Pathway ◽  
Plaque Deposition ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α ◽  
Neurological Illnesses

Abstract Background Suan-Zao-Ren Decoction (SZRD) has been widely used to treat neurological illnesses, including dementia, insomnia and depression. However, the mechanisms underlying SZRD’s improvement in cognitive function remain unclear. In this study, we examined SZRD’s effect on APP/PS1 transgenic mice and mechanisms associated with SZRD’s action in alleviating neuroinflammation and improving synaptic plasticity. Methods The APP/PS1 mice were treated with different dosages of SZRD (12.96 and 25.92 g/kg/day, in L-SZRD and H-SZRD groups, respectively) for 4 weeks. Morris water maze was conducted to determine changes in behaviors of the mice after the treatment. Meanwhile, in the samples of the hippocampus, Nissl staining and Golgi-Cox staining were used to detect synaptic plasticity. ELISA was applied to assess the expression levels of Aβ1−40 and Aβ1−42 in the hippocampus of mice. Western blot (WB) was employed to test the protein expression level of Aβ1−42, APP, ADAM10, BACE1, PS1, IDE, IBA1, GFAP, PSD95 and SYN, as well as the expressions of JAK2, STAT3 and their phosphorylation patterns to detect the involvement of JAK2/STAT3 pathway. Besides, we examined the serum and hippocampal contents of IL-1β, IL-6 and TNF-α through ELISA. Results Compared to the APP/PS1 mice without any treatment, SZRD, especially the L-SZRD, significantly ameliorated cognitive impairment of the APP/PS1 mice with decreases in the loss of neurons and Aβ plaque deposition as well as improvement of synaptic plasticity in the hippocampus (P < 0.05 or 0.01). Also, SZRD, in particular, the L-SZRD markedly inhibited the serum and hippocampal concentrations of IL-6, IL-1β and TNF-α, while reducing the expression of p-JAK2-Tyr1007 and p-STAT3-Tyr705 in the hippocampus of the APP/PS1 mice (P < 0.05 or 0.01). Conclusions The SZRD, especially the L-SZRD, may improve the cognitive impairment and ameliorate the neural degeneration in APP/PS1 transgenic mice through inhibiting Aβ accumulation and neuroinflammation via the JAK2/STAT3 pathway.

scholarly journals Dysregulation of Astrocyte–Neuronal Communication in Alzheimer’s Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7887
Author(s):  
Carmen Nanclares ◽  
Andres Mateo Baraibar ◽  
Alfonso Araque ◽  
Paulo Kofuji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Neuronal Excitability ◽  
Active Role ◽  
Ionic Homeostasis ◽  
Neuronal Communication ◽  
Structural Support

Recent studies implicate astrocytes in Alzheimer’s disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters. Here, we review how this “active” role of astrocytes at synapses could contribute to synaptic and neuronal network dysfunction and cognitive impairment in AD.

scholarly journals Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Soriano Roque ◽  
Mehdi Hooshmandi ◽  
Laura Neagu-Lund ◽  
Shelly Yin ◽  
Noosha Yousefpour ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
General Anesthesia ◽  
Preventive Treatment ◽  
Intranasal Insulin ◽  
Translational Repressor ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

scholarly journals Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction

2021 ◽  
pp. 1-16
Author(s):  
Wei Wei ◽  
Yinghua Liu ◽  
Chunling Dai ◽  
Narjes Baazaoui ◽  
Yunn-Chyn Tung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Early Development ◽  
Neurodegenerative Disorder ◽  
Synaptic Dysfunction ◽  
Early Postnatal Development ◽  
Wild Type Female

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction. Objective: To explore strategies for early intervention to prevent Alzheimer’s disease. Methods: In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated. Results: P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC/PKC, MEK/ERK and PI3K/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice. Conclusion: These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.

scholarly journals Dissociation between CA3-CA1 Synaptic Plasticity and Associative Learning in TgNTRK3 Transgenic Mice

2007 ◽  
Vol 27 (9) ◽  
pp. 2253-2260 ◽  
Author(s):  
I. Sahun ◽  
J. M. Delgado-Garcia ◽  
A. Amador-Arjona ◽  
A. Giralt ◽  
J. Alberch ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Associative Learning
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