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

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.