MicroRNA-128-3p Affects Neuronal Apoptosis and Neurobehavior in Cerebral Palsy Rats by Targeting E3 Ubiquitin-Linking...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Cerebral palsy (CP) is a debilitating neurological disorder often resulting from hypoxic-ischemic (HI) injury.
• Understanding the molecular mechanisms underlying neuronal apoptosis and neurobehavioral deficits in CP is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of microRNA-128-3p (miR-128-3p) in neuronal apoptosis and neurobehavioral outcomes in a rat model of HI-induced CP.
• To elucidate the molecular pathway involving Smurf2 and YY1 that mediates the effects of miR-128-3p in CP.

Main Methods:

• Establishment of an in vivo HI model in neonatal rats and an in vitro oxygen-glucose deprivation (OGD) model using primary cortical neurons.
• Assessment of neurobehavioral performance, neurological injury (histopathology, apoptosis assays), and expression levels of miR-128-3p, Smurf2, and YY1 using molecular and biochemical techniques.
• Mechanistic investigations including bioinformatics analysis, dual luciferase reporter assays, RIP, Co-IP, and ubiquitination assays to confirm the interactions between miR-128-3p, Smurf2, and YY1.

Main Results:

• In HI-CP rats, miR-128-3p and YY1 expression were elevated, while Smurf2 expression was decreased.
• Downregulation of miR-128-3p or overexpression of Smurf2 ameliorated neurobehavioral deficits, reduced neuronal apoptosis, and increased Nestin and NGF expression in HI-CP rats.
• miR-128-3p directly targets Smurf2, suppressing its expression by reducing YY1 ubiquitination and degradation. Overexpression of YY1 reversed the protective effects of miR-128-3p downregulation.

Conclusions:

• miR-128-3p plays a detrimental role in HI-induced CP by suppressing Smurf2 and consequently increasing YY1 expression, leading to enhanced neuronal apoptosis and impaired neurobehavior.
• Inhibition of miR-128-3p represents a potential therapeutic strategy for CP by restoring the Smurf2/YY1 balance, reducing neuronal injury, and improving neurological function.