A novel structure associated with aging is augmented in the DPP6-KO mouse brain.
Acta Neuropathol Commun
; 8(1): 197, 2020 11 23.
Article
em En
| MEDLINE
| ID: mdl-33225987
ABSTRACT
In addition to its role as an auxiliary subunit of A-type voltage-gated K+ channels, we have previously reported that the single transmembrane protein Dipeptidyl Peptidase Like 6 (DPP6) impacts neuronal and synaptic development. DPP6-KO mice are impaired in hippocampal-dependent learning and memory and exhibit smaller brain size. Using immunofluorescence and electron microscopy, we report here a novel structure in hippocampal area CA1 that was significantly more prevalent in aging DPP6-KO mice compared to WT mice of the same age and that these structures were observed earlier in development in DPP6-KO mice. These novel structures appeared as clusters of large puncta that colocalized NeuN, synaptophysin, and chromogranin A. They also partially labeled for MAP2, and with synapsin-1 and VGluT1 labeling on their periphery. Electron microscopy revealed that these structures are abnormal, enlarged presynaptic swellings filled with mainly fibrous material with occasional peripheral, presynaptic active zones forming synapses. Immunofluorescence imaging then showed that a number of markers for aging and especially Alzheimer's disease were found as higher levels in these novel structures in aging DPP6-KO mice compared to WT. Together these results indicate that aging DPP6-KO mice have increased numbers of novel, abnormal presynaptic structures associated with several markers of Alzheimer's disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Terminações Pré-Sinápticas
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Dipeptidil Peptidases e Tripeptidil Peptidases
/
Região CA1 Hipocampal
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article