Sustained Microglial Activation Promotes Synaptic Loss and Neuronal Dysfunction after Recovery from ZIKV Infection

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Zika virus (ZIKV) poses a global health threat, causing microcephaly and neurological issues.
• Mechanisms of ZIKV-induced adult neurological complications and persistent alterations post-recovery are not fully understood.
• Elevated proinflammatory cytokines and lasting neurological changes are reported after ZIKV infection.

Purpose of the Study:

• To investigate the in vivo mechanisms of ZIKV-induced neuroinflammation and neurodegeneration.
• To elucidate the role of microglial activation in persistent neurological alterations post-ZIKV recovery.
• To identify molecular markers of ZIKV-related brain damage.

Main Methods:

• Infection of mice with ZIKV and monitoring of viral RNA loads in the brain.
• RNA sequencing of the cerebral cortex at 7 and 21 days post-infection.
• Histological analysis to assess neuronal cell death, neurite morphology, and microglial activation.
• Measurement of phospho-Tau levels as a marker of neurodegeneration.

Main Results:

• ZIKV RNA loads peaked at 7 days and normalized by 21 days post-infection in mouse brains.
• Gene expression analysis revealed upregulation of neuroinflammation and microglial activation markers.
• Histology showed neuronal cell death, altered neurite morphology, and sustained microglial activation.
• Increased phospho-Tau levels correlated with sustained microglial activation, indicating ongoing neurodegeneration.

Conclusions:

• Persistent microglial activation is a key factor in ZIKV-induced neuronal dysfunction after viral clearance.
• Sustained microglial activation contributes to neurodegeneration, evidenced by elevated phospho-Tau levels.
• This study provides insights into the molecular pathogenesis of ZIKV-related brain abnormalities, highlighting neuroinflammation's role.