A novel structure associated with aging is augmented in the DPP6-KO mouse brain
Lin Lin1, Ronald S Petralia2, Ross Lake3
1Molecular Neurophysiology and Biophysics Section, Program in Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 35 Lincoln Drive, MSC 3715, Building 35, Room 3C-905, Bethesda, MD, 20892-3715, USA.
Acta Neuropathologica Communications
|November 23, 2020
Summary
Dipeptidyl Peptidase Like 6 (DPP6) deficiency in mice leads to novel abnormal presynaptic structures. These structures are linked to aging and Alzheimer's disease markers, impacting brain development and memory.
Area of Science:
- Neuroscience
- Molecular Biology
- Aging Research
Background:
- Dipeptidyl Peptidase Like 6 (DPP6) is crucial for neuronal and synaptic development.
- DPP6 deficiency impairs hippocampal learning, memory, and brain size.
- The role of DPP6 in aging and neurodegenerative diseases remains unclear.
Purpose of the Study:
- To investigate novel structures in aging Dipeptidyl Peptidase Like 6 knockout (DPP6-KO) mice.
- To characterize the composition and synaptic features of these structures.
- To assess the association of these structures with aging and Alzheimer's disease markers.
Main Methods:
- Immunofluorescence microscopy to identify and localize novel structures.
- Electron microscopy for ultrastructural analysis of the novel structures.
- Colocalization studies with neuronal, synaptic, and aging/Alzheimer's disease markers.
Main Results:
- Aging DPP6-KO mice exhibit significantly more novel presynaptic structures in hippocampal area CA1 compared to wild-type (WT) mice.
- These structures are enlarged presynaptic swellings containing fibrous material and peripheral active zones.
- Elevated levels of aging and Alzheimer's disease markers were detected within these structures in DPP6-KO mice.
Conclusions:
- DPP6 deficiency leads to the formation of abnormal presynaptic structures associated with aging.
- These structures show increased prevalence and earlier onset in DPP6-KO mice.
- The findings suggest a potential link between DPP6, abnormal presynaptic formations, and Alzheimer's disease pathology.
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