Functional connectivity changes in mouse models of maple syrup urine disease

Area of Science:

• Neuroscience
• Metabolic Disorders
• Inborn Errors of Metabolism

Background:

• Maple syrup urine disease (MSUD) is a rare metabolic disorder causing neurodevelopmental injury.
• Structural neuroimaging reveals edema and white matter injury in MSUD, but functional neuroimaging data are lacking.

Purpose of the Study:

• To investigate resting-state functional connectivity in mouse models of MSUD using widefield optical imaging.
• To determine the impact of a high-protein diet challenge on functional connectivity in MSUD models.

Main Methods:

• Utilized two brain-specific mouse models: astrocyte-specific knockout and whole-brain knockout for MSUD.
• Performed widefield optical imaging to assess functional connectivity before and after a 1-week high-protein diet.
• Analyzed data using seed-based functional connectivity and cluster-based inference.

Main Results:

• Astrocyte-specific knockout mice showed increased contralateral functional connectivity in the somatosensory cortex post-diet.
• Whole-brain knockout mice exhibited similar baseline connectivity patterns that persisted after diet initiation.
• Contrary to hypotheses, MSUD led to increased, not decreased, functional connectivity strength.

Conclusions:

• Inborn errors of metabolism, such as MSUD, significantly alter functional connectivity networks in the brain.
• The observed increase in functional connectivity in MSUD models warrants further investigation into underlying mechanisms.
• Functional neuroimaging may offer potential biomarkers for MSUD that could be translated to clinical practice.