iTBS Improves Behavioral Abnormalities and Synaptic Defects in Fmr1 KO Rats by Regulating the Autophagy Pathway

Area of Science:

• Neuroscience
• Genetics
• Cell Biology

Background:

• Fragile X syndrome (FXS) pathogenesis involves synaptic dysfunction linked to abnormal autophagy.
• Intermittent theta burst stimulation (iTBS) shows therapeutic promise for neurological disorders, but its efficacy in FXS is unknown.

Purpose of the Study:

• To investigate if iTBS can ameliorate behavioral abnormalities and synaptic dysfunction in FXS models.
• To explore the underlying mechanism of iTBS, focusing on autophagy pathway modulation.

Main Methods:

• Utilized Fmr1 knockout (KO) rats as an FXS model.
• Administered a 2-week iTBS intervention.
• Assessed behavioral changes, hippocampal neural oscillations, synaptic structure, and autophagy-related proteins.

Main Results:

• iTBS significantly improved behavioral deficits in Fmr1 KO rats.
• iTBS attenuated heightened hippocampal theta-gamma phase-amplitude coupling.
• Treatment restored synaptic function, CaMKK2 activity, and autophagy in the hippocampus.

Conclusions:

• iTBS demonstrates beneficial effects on aberrant behavior and synaptic defects in FXS models.
• The CaMKK2-dependent autophagy pathway is implicated in iTBS's therapeutic effects.
• iTBS holds potential as a therapeutic strategy for individuals with FXS.