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CDR1as regulates α-synuclein-mediated ischemic brain damage by controlling miR-7 availability.
Mehta, Suresh L; Chokkalla, Anil K; Bathula, Saivenkateshkomal; Arruri, Vijay; Chelluboina, Bharath; Vemuganti, Raghu.
Afiliación
  • Mehta SL; Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
  • Chokkalla AK; Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
  • Bathula S; Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
  • Arruri V; Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
  • Chelluboina B; Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
  • Vemuganti R; Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
Mol Ther Nucleic Acids ; 31: 57-67, 2023 Mar 14.
Article en En | MEDLINE | ID: mdl-36618263
Transient focal ischemia decreased microRNA-7 (miR-7) levels, leading to derepression of its major target α-synuclein (α-Syn) that promotes secondary brain damage. Circular RNA CDR1as is known to regulate miR-7 abundance and function. Hence, we currently evaluated its functional significance after focal ischemia. Transient middle cerebral artery occlusion (MCAO) in adult mice significantly downregulated both CDR1as and miR-7 levels in the peri-infarct cortex between 3 and 72 h of reperfusion. Interestingly, neither pri-miR-7a nor 7b was altered in the ischemic brain. Intracerebral injection of an AAV9 vector containing a CDR1as gene significantly increased CDR1as levels by 21 days that persisted up to 4 months without inducing any observable toxicity in both sham and MCAO groups. Following transient MCAO, there was a significant increase in miR-7 levels and CDR1as binding to Ago2/miR-7 in the peri-infarct cortex of AAV9-CDR1as cohort compared with AAV9-Control cohort at 1 day of reperfusion. CDR1as overexpression significantly suppressed post-stroke α-Syn protein induction, promoted motor function recovery, decreased infarct size, and curtailed the markers of apoptosis, autophagy mitochondrial fragmentation, and inflammation in the post-stroke brain compared with AAV9-Control-treated cohort. Overall, our findings imply that CDR1as reconstitution is neuroprotective after stroke, probably by protecting miR-7 and preventing α-Syn-mediated neuronal death.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos