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The microRNA miR-7a-5p ameliorates ischemic brain damage by repressing α-synuclein.

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Therapeutic miR-7 mimics reduced brain damage and improved function after ischemic stroke in rodents. This microRNA therapy targets alpha-synuclein, offering potential for stroke recovery.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biomedical Research

Background:

  • Ischemic stroke causes significant disability and mortality.
  • Cerebral microRNA expression changes after stroke, with decreased miR-7a-5p (miR-7) observed.
  • Previous studies indicated temporal changes in cerebral microRNAs following focal ischemia.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of a miR-7 mimic oligonucleotide in rodent models of cerebral ischemia.
  • To assess the impact of miR-7 mimic treatment on lesion volume and functional recovery.
  • To investigate the underlying molecular mechanisms, including the role of alpha-synuclein (α-Syn).

Main Methods:

  • Rodents (rats and mice) were subjected to transient middle cerebral artery occlusion (tMCAO).
  • miR-7 mimic oligonucleotide was administered locally or systemically, pre- or post-ischemia.
  • Lesion volume, motor and cognitive functions, and α-Syn expression were assessed.
  • Gene deletion of α-Syn was performed to confirm its role in miR-7 mimic-mediated neuroprotection.

Main Results:

  • Decreased miR-7 expression was confirmed in young and aged rats of both sexes post-ischemia.
  • Pre- or postischemic miR-7 mimic treatment reduced lesion volume in both sexes and ages.
  • Systemic miR-7 mimic treatment in mice post-ischemia decreased lesion volume and improved functional recovery.
  • miR-7 mimic treatment reduced postischemic α-Syn induction, a key mediator of neuronal death.
  • Deletion of the α-Syn gene abolished miR-7 mimic-dependent neuroprotection and functional recovery.
  • miR-7 was confirmed to directly bind and repress the α-Syn transcript.

Conclusions:

  • miR-7 mimic oligonucleotide demonstrates significant therapeutic potential for treating ischemic stroke.
  • The neuroprotective effects of miR-7 mimics are mediated, in part, by the repression of α-Syn.
  • This approach may offer a novel strategy to minimize stroke-induced brain damage and disability.