Impact of neural stem cell‐derived extracellular vesicles on mitochondrial dysfunction, sirtuin 1 level, and synaptic deficits in Alzheimer’s disease

2020 ◽  
Vol 154 (5) ◽  
pp. 502-518 ◽  
Author(s):  
Bo Li ◽  
Jianhui Liu ◽  
Guojun Gu ◽  
Xu Han ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Mitochondrial Dysfunction ◽  
Neural Stem Cell ◽  
Extracellular Vesicles ◽  
Sirtuin 1

scholarly journals Mitigation of Alzheimer’s Disease Neuropathologies by Human Neural Stem Cell-derived Extracellular Vesicles

2020 ◽  
Author(s):  
Lauren A Apodaca ◽  
Al Anoud D Baddour ◽  
Camilo Garcia ◽  
Leila Alikhani ◽  
Erich Giedzinski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Extracellular Vesicles ◽  
Age Groups ◽  
Synaptic Function ◽  
Neuroprotective Effects ◽  
Partial Restoration ◽  
Human Neural Stem Cell

Abstract Background: Regenerative therapies to mitigate Alzheimer’s disease (AD) neuropathology have shown very limited success. In the recent era, extracellular vesicles (EV) derived from multipotent and pluripotent stem cells have shown considerable promise for the treatment of dementia and many neurodegenerative conditions. Methods: Using the 5xFAD accelerated transgenic mouse model of AD, we now show the regenerative potential of human neural stem cell (hNSC)-derived EV on the neurocognitive and neuropathologic outcomes in the AD brain. Two or six-month-old 5xFAD mice received single or two intra-venous (retro-orbital vein, RO) injections of hNSC-derived EV, respectively.Results: RO treatment using hNSC-derived EV restored fear extinction memory consolidation and reduced anxiety-related behaviors 4-6 weeks post-injection. EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups. These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice. Importantly, EV treatment protected against synaptic loss in the AD brain that paralleled improved cognition. MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function. Conclusions: Collectively, these data demonstrate the neuroprotective effects of systemic administration of stem cell-derived EV for remediation of behavioral and molecular AD neuropathologies.

scholarly journals Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lauren A. Apodaca ◽  
Al Anoud D. Baddour ◽  
Camilo Garcia ◽  
Leila Alikhani ◽  
Erich Giedzinski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Extracellular Vesicles ◽  
Age Groups ◽  
Synaptic Function ◽  
Neuroprotective Effects ◽  
Partial Restoration ◽  
Human Neural Stem Cell

Abstract Background Regenerative therapies to mitigate Alzheimer’s disease (AD) neuropathology have shown very limited success. In the recent era, extracellular vesicles (EVs) derived from multipotent and pluripotent stem cells have shown considerable promise for the treatment of dementia and many neurodegenerative conditions. Methods Using the 5xFAD accelerated transgenic mouse model of AD, we now show the regenerative potential of human neural stem cell (hNSC)-derived EVs on the neurocognitive and neuropathologic hallmarks in the AD brain. Two- or 6-month-old 5xFAD mice received single or two intra-venous (retro-orbital vein, RO) injections of hNSC-derived EVs, respectively. Results RO treatment using hNSC-derived EVs restored fear extinction memory consolidation and reduced anxiety-related behaviors 4–6 weeks post-injection. EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups. These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice. Importantly, EV treatment protected against synaptic loss in the AD brain that paralleled improved cognition. MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function. Conclusions Collectively, these data demonstrate the neuroprotective effects of systemic administration of stem cell-derived EVs for remediation of behavioral and molecular AD neuropathologies.

P3-345: Restoration of memory in mouse models of Alzheimer's disease and neuronal loss: A new paradigm using human neural stem cell therapy

2012 ◽  
Vol 8 (4S_Part_16) ◽  
pp. P577-P578
Author(s):  
Mathew Blurton-Jones ◽  
Rahasson Ager ◽  
Joy Nerhus ◽  
Andy Agazaryan ◽  
Stephen Huhn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Cell Therapy ◽  
Neural Stem Cell ◽  
Mouse Models ◽  
Stem Cell Therapy ◽  
Neuronal Loss ◽  
New Paradigm ◽  
Human Neural Stem Cell

scholarly journals KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2748
Author(s):  
Tohid Siddiqui ◽  
Prabesh Bhattarai ◽  
Stanislava Popova ◽  
Mehmet Ilyas Cosacak ◽  
Sanjeev Sariya ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Late Onset ◽  
Association Studies ◽  
Neural Regeneration ◽  
Adult Zebrafish ◽  
Amyloid Toxicity ◽  
Model Of Alzheimer’S Disease

Neurogenesis decreases in Alzheimer’s disease (AD) patients, suggesting that restoring the normal neurogenic response could be a disease modifying intervention. To study the mechanisms of pathology-induced neuro-regeneration in vertebrate brains, zebrafish is an excellent model due to its extensive neural regeneration capacity. Here, we report that Kynurenic acid (KYNA), a metabolite of the amino acid tryptophan, negatively regulates neural stem cell (NSC) plasticity in adult zebrafish brain through its receptor, aryl hydrocarbon receptor 2 (Ahr2). The production of KYNA is suppressed after amyloid-toxicity through reduction of the levels of Kynurenine amino transferase 2 (KAT2), the key enzyme producing KYNA. NSC proliferation is enhanced by an antagonist for Ahr2 and is reduced with Ahr2 agonists or KYNA. A subset of Ahr2-expressing zebrafish NSCs do not express other regulatory receptors such as il4r or ngfra, indicating that ahr2-positive NSCs constitute a new subset of neural progenitors that are responsive to amyloid-toxicity. By performing transcriptome-wide association studies (TWAS) in three late onset Alzheimer disease (LOAD) brain autopsy cohorts, we also found that several genes that are components of KYNA metabolism or AHR signaling are differentially expressed in LOAD, suggesting a strong link between KYNA/Ahr2 signaling axis to neurogenesis in LOAD.

Sign in / Sign up

Export Citation Format

Share Document