Bibliographic Details
| Title: |
Extracellular vesicles from hiPSC-NSCs can prevent peripheral inflammation-induced cognitive dysfunction with inflammasome inhibition and improved neurogenesis in the hippocampus |
| Authors: |
Gunel Ayyubova, Maheedhar Kodali, Raghavendra Upadhya, Leelavathi N. Madhu, Sahithi Attaluri, Yogish Somayaji, Bing Shuai, Shama Rao, Goutham Shankar, Ashok K. Shetty |
| Source: |
Journal of Neuroinflammation, Vol 20, Iss 1, Pp 1-26 (2023) |
| Publisher Information: |
BMC, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Neurology. Diseases of the nervous system |
| Subject Terms: |
Activated microglia, Cognitive dysfunction, Extracellular vesicles, Human neural stem cells, Human pluripotent stem cells, NLRP3 inflammasomes, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: |
Abstract Extracellular vesicles (EVs) released by human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs) are enriched with miRNAs and proteins capable of mediating robust antiinflammatory activity. The lack of tumorigenic and immunogenic properties and ability to permeate the entire brain to incorporate into microglia following intranasal (IN) administrations makes them an attractive biologic for curtailing chronic neuroinflammation in neurodegenerative disorders. We tested the hypothesis that IN administrations of hiPSC-NSC-EVs can alleviate chronic neuroinflammation and cognitive impairments induced by the peripheral lipopolysaccharide (LPS) challenge. Adult male, C57BL/6J mice received intraperitoneal injections of LPS (0.75 mg/kg) for seven consecutive days. Then, the mice received either vehicle (VEH) or hiPSC-NSC-EVs (~ 10 × 109 EVs/administration, thrice over 6 days). A month later, mice in all groups were investigated for cognitive function with behavioral tests and euthanized for histological and biochemical studies. Mice receiving VEH after LPS displayed deficits in associative recognition memory, temporal pattern processing, and pattern separation. Such impairments were associated with an increased incidence of activated microglia presenting NOD-, LRR-, and pyrin domain containing 3 (NLRP3) inflammasomes, elevated levels of NLRP3 inflammasome mediators and end products, and decreased neurogenesis in the hippocampus. In contrast, the various cognitive measures in mice receiving hiPSC-NSC-EVs after LPS were closer to naive mice. Significantly, these mice displayed diminished microglial activation, NLRP3 inflammasomes, proinflammatory cytokines, and a level of neurogenesis matching age-matched naïve controls. Thus, IN administrations of hiPSC-NSC-EVs are an efficacious approach to reducing chronic neuroinflammation-induced cognitive impairments. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1742-2094 |
| Relation: |
https://doaj.org/toc/1742-2094 |
| DOI: |
10.1186/s12974-023-02971-y |
| Access URL: |
https://doaj.org/article/babb73ba873d43e5aaae3a4f6631489f |
| Accession Number: |
edsdoj.babb73ba873d43e5aaae3a4f6631489f |
| Database: |
Directory of Open Access Journals |
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