Heterophyllin B, a cyclopeptide from Pseudostellaria heterophylla , enhances cognitive function via neurite outgrowth and synaptic plasticity

2021 ◽  
Author(s):  
Zhiyou Yang ◽  
Cai Zhang ◽  
Xiaohong Li ◽  
Zhihui Ma ◽  
Yuewei Ge ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Neurite Outgrowth ◽  
Pseudostellaria Heterophylla

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 Exosomal miR-132-3p from Mesenchymal Stromal Cells Improve Synaptic Dysfunction and Cognitive Decline in Vascular Dementia

2021 ◽  
Author(s):  
Xiaotang Ma ◽  
Yan Wang ◽  
Yumeng Shi ◽  
Suqing Li ◽  
Jinhua Liu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Stromal Cells ◽  
Memory Deficit ◽  
Synaptic Dysfunction ◽  
Spine Density ◽  
Neuron Number ◽  
Neurite Elongation ◽  
Dendritic Spine Density ◽  
Gsk 3Β

Abstract Background/Aims: Vascular dementia (VD) results in cognition and memory deficit. Exosomes and their carried microRNAs (miRs) contribute to the neuroprotective effects of mesenchymal stromal cells, and miR-132-3p plays a key role in neuron plasticity. Here we investigated the role and underlying mechanism of MSC EX and their miR-132-3p cargo in rescuing cognition and memory deficit in VD mice. Methods: Bilateral carotid artery occlusion was used to generate a VD mouse model. MiR-132-3p and MSC EX levels in the hippocampus and cortex were measured. At 24 h post-VD induction, mice were administered with MSC EX infected with control lentivirus (EXCon), pre-miR-132-3p-expressing lentivirus (EXmiR−132−3p), or miR-132-3p antago lentivirus (EXantagomiR−132−3p) intravenously. Behavioral and cognitive tests were performed and the mice were sacrificed in 21 days after VD. The effects of MSC EX on neuron number, synaptic plasticity, dendritic spine density, and Aβ and p-Tau levels in the hippocampus and cortex were determined. The effects of MSC EX on oxygen-glucose deprivation (OGD)-injured neurons with respect to apoptosis, and neurite elongation and branching were determined. Finally, the expression levels of Ras, phosphorylation of Akt, GSK-3β, and Tau were also measured. Results: Compared with normal mice, VD mice exhibited significantly decreased miR-132-3p and MSC EX levels in the cortex and hippocampus. Compared with EXCon treatment, the infusion of EXmiR−132−3p was more effective at improving cognitive function and increasing miR-132-3p level, neuron number, synaptic plasticity, and dendritic spine density, while decreasing Aβ and p-Tau levels in the cortex and hippocampus of VD mice. Conversely, EXantagomiR−132−3p treatment significantly decreased miR-132-3p expression in cortex and hippocampus, as well as attenuated EXmiR−132−3p treatment-induced functional improvement. In vitro, EXmiR−132−3p treatment inhibited RASA1 protein expression, but increased Ras and the phosphorylation of Akt and GSK-3β, and decreased p-Tau levels in primary neurons by delivering miR-132-3p, which resulted in reduced apoptosis, and increased neurite elongation and branching in OGD-injured neurons. Conclusions: Our studies suggest that miR-132-3p cluster-enriched MSC EX promotes the recovery of cognitive function by improving neuronal and synaptic dysfunction through activation of the Ras/Akt/GSK-3β pathway induced by downregulation of RASA1.

Social housing promotes cognitive function through enhancing synaptic plasticity in APP/PS1 mice

2019 ◽  
Vol 368 ◽  
pp. 111910 ◽  
Author(s):  
Feiyu Liang ◽  
Shen Yang ◽  
Yang Zhang ◽  
Tianpao Hao
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Social Housing

scholarly journals Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice

2014 ◽  
Vol 20 (6) ◽  
pp. 659-663 ◽  
Author(s):  
Saul A Villeda ◽  
Kristopher E Plambeck ◽  
Jinte Middeldorp ◽  
Joseph M Castellano ◽  
Kira I Mosher ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Age Related

scholarly journals Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

2011 ◽  
Vol 32 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Fei Jing ◽  
Masaki Mogi ◽  
Akiko Sakata ◽  
Jun Iwanami ◽  
Kana Tsukuda ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Angiotensin Ii ◽  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Receptor Agonist ◽  
Laser Speckle ◽  
Morris Water Maze Test ◽  
Direct Stimulation ◽  
Stimulation Of

We examined the possibility that direct stimulation of the angiotensin II type 2 (AT2) receptor by a newly generated direct AT2 receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT2 receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B2 receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT2 receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT2 receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.

P2-030: DPP-4 inhibitor improves brain insulin sensitivity, but fails to restore hippocampal synaptic plasticity and cognitive function in testosterone-deprived obese rats

2015 ◽  
Vol 11 (7S_Part_10) ◽  
pp. P492-P493
Author(s):  
Hiranya Pintana ◽  
Wanpitak Pongkan ◽  
Wasana Pratchayasakul ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Insulin Sensitivity ◽  
Hippocampal Synaptic Plasticity ◽  
Brain Insulin ◽  
Obese Rats
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