ArticleCellular and molecular neurobiology2024
Enhanced Spine Stability and Survival Lead to Increases in Dendritic Spine Density as an Early Response to Local Alpha-Synuclein Overexpression in Mouse Prefrontal Cortex.
Article in Cellular and molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 4 citations in OpenAlex.
- Gray Matter Microstructure Measured Using Diffusion Imaging as a Biomarker of Severity in Lewy Body Diseases.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Role of α-Synuclein in the Prefrontal Cortex: From Physiological Synaptic Modulation to Synaptic Failure in Parkinson's Disease.Biomedicines · 2026Review
- Short-term effects of ambient air pollution on musculoskeletal diseases in Yangzhou during 2019-2022.BMC public health · 2025Article
- Chronic stress induces depression-like behaviors and Parkinsonism via upregulating α-synuclein.NPJ Parkinson's disease · 2025Article
- Thy1-YFP: an effective tool for single cell tracing from neuronal progenitors to mature functionally active neurons.Cell death discovery · 2025Article
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8 authors at 1 institution in 1 country.
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Abstract
Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. However, the impact of local pathology in the cortex is unknown. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then used in vivo 2-photon microscopy to image awake head-fixed mice via an implanted chronic cranial window to assess the early consequences of alpha-Synuclein overexpression in the weeks following overexpression. We imaged apical tufts of Layer V pyramidal neurons in the PFC of Thy1-YFP transgenic mice at 1-week intervals from 1 to 2 weeks before and 9 weeks following viral overexpression, allowing analysis of dynamic changes in dendritic spines. We found an increase in the relative dendritic spine density following local overexpression of alpha-Synuclein, beginning at 5 weeks post-injection, and persisting for the remainder of the study. We found that alpha-Synuclein overexpression led to an increased percentage and longevity of newly-persistent spines, without significant changes in the total density of newly formed or eliminated spines. A follow-up study utilizing confocal microscopy revealed that the increased spine density is found in cortical cells within the alpha-Synuclein injection site, but negative for alpha-Synuclein phosphorylation at Serine-129, highlighting the potential for effects of dose and local circuits on spine survival. These findings have important implications for the physiological role and early pathological stages of alpha-Synuclein in the cortex.
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