Neuroimaging and Transcriptomic Insights Into Iron Accumulation and Glymphatic Dysfunction in Olfactory Dysfunction

Area of Science:

• Neuroimaging
• Neurobiology
• Transcriptomics

Background:

• Olfactory dysfunction (OD) is linked to inflammation and neurotoxins, but mechanisms are unclear.
• Investigating glymphatic function, iron dysregulation, and gene expression may reveal OD biomarkers.
• Understanding these factors is crucial for developing recovery strategies.

Purpose of the Study:

• To explore the neurobiological underpinnings of olfactory dysfunction.
• To investigate the roles of glymphatic function, iron dysregulation, and transcriptomic changes in OD.
• To identify potential biomarkers for OD diagnosis and prognosis.

Main Methods:

• A multimodal MRI approach combining BOLD-CSF coupling and quantitative susceptibility mapping (QSM) was used.
• Transcriptomic profiling was integrated with QSM to analyze iron accumulation and gene expression.
• Data were collected from post-viral OD (PVOD), post-traumatic OD (PTOD), and healthy control (HC) groups.

Main Results:

• PVOD showed increased iron in olfactory memory regions, correlating with genes for neuronal organization and signaling.
• PVOD exhibited enhanced glymphatic activity (stronger BOLD-CSF coupling) compared to controls.
• Complete recovery correlated with the strongest BOLD-CSF coupling, indicating improved toxin clearance.

Conclusions:

• Olfactory dysfunction is associated with abnormal iron accumulation and altered glymphatic function.
• Transcriptomic signatures suggest neuroplasticity plays a role in OD.
• Improved glymphatic clearance and neuronal remodeling may drive recovery, offering potential biomarkers.