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Brain structure and synaptic protein expression alterations after antidepressant treatment in a Wistar-Kyoto rat
1Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Shanxi Provincial Key Laboratory of Brain Science and Neuropsychiatric Diseases, First Hospital of Shanxi Medical University, Taiyuan, China; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Background:
Structural MRI has demonstrated brain alterations in depression pathology and antidepressants treatment. While synaptic plasticity has been previously proposed as the potential underlying mechanism of MRI findings at a cellular and molecular scale, there is still insufficient evidence to link the MRI findings and synaptic plasticity mechanisms in depression pathology.
Methods:
In this study, a Wistar-Kyoto (WKY) depression rat model was treated with antidepressants (citalopram or Jie-Yu Pills) and tested in a series of behavioral tests and a 7.0 MRI scanner. We then measured dendritic spine density within altered brain regions. We also examined expression of synaptic marker proteins (PSD-95 and SYP).
Results:
WKY rats exhibited depression-like behaviors in the sucrose preference test (SPT) and forced swim test (FST), and anxiety-like behaviors in the open field test (OFT). Both antidepressants reversed behavioral changes in SPT and OFT but not in FST. We found a correlation between SPT performance and brain volumes as detected by MRI. All structural changes were consistent with alterations of the corpus callosum (white matter), dendritic spine density, as well as PSD95 and SYP expression at different levels. Two antidepressants similarly reversed these macro- and micro-changes.
Limitations:
The single dose of antidepressants was the major limitation of this study. Further studies should focus on the white matter microstructure changes and myelin-related protein alterations, in addition to comparing the effects of ketamine.
Conclusion:
Translational evidence links structural MRI changes and synaptic plasticity alterations, which promote our understanding of SPT mechanisms and antidepressant response in WKY rats.
Insights
This study links brain structure changes seen in MRI scans to synaptic plasticity in a rat model of depression. Antidepressants improved behaviors and reversed these structural and molecular changes.
Area of Science:
- Neuroscience
- Psychiatry
- Medical Imaging
Background:
- Structural magnetic resonance imaging (MRI) reveals brain alterations in depression and antidepressant treatment.
- Synaptic plasticity is a proposed mechanism for MRI findings, but direct evidence linking it to depression pathology is limited.
Purpose of the Study:
- To investigate the relationship between MRI-detected brain alterations and synaptic plasticity in a Wistar-Kyoto (WKY) rat model of depression.
- To assess the effects of antidepressants on behavioral, structural, and molecular changes in this depression model.
Main Methods:
- WKY rats, a depression model, were treated with antidepressants (citalopram or Jie-Yu Pills).
- Behavioral tests (sucrose preference, forced swim, open field) were conducted.
- Structural MRI was used to assess brain volumes, followed by measurement of dendritic spine density and synaptic marker proteins (PSD-95, SYP) in relevant brain regions.
Main Results:
- WKY rats displayed depression- and anxiety-like behaviors.
- Antidepressants improved sucrose preference and open field test performance but not forced swim test results.
- A correlation was found between sucrose preference test performance and MRI-detected brain volumes.
- Structural MRI changes, dendritic spine density, and synaptic marker protein expression were altered in WKY rats and reversed by antidepressants.
Conclusions:
- The study provides translational evidence linking structural MRI changes with synaptic plasticity alterations in a rat model of depression.
- These findings enhance the understanding of sucrose preference test mechanisms and antidepressant response.
