Eintrag weiter verarbeiten
Buchumschlag von Effective expression of Drebrin in hippocampus improves cognitive function and alleviates lesions of Alzheimer's disease in APP (swe)/PS1 (ΔE9) mice
Verfügbar über Open Access

Effective expression of Drebrin in hippocampus improves cognitive function and alleviates lesions of Alzheimer's disease in APP (swe)/PS1 (ΔE9) mice

Gespeichert in:

Bibliographische Detailangaben
Zeitschriftentitel: CNS Neuroscience & Therapeutics
Personen und Körperschaften: Liu, Yan, Xu, Yan‐Feng, Zhang, Ling, Huang, Lan, Yu, Pin, Zhu, Hua, Deng, Wei, Qin, Chuan
In: CNS Neuroscience & Therapeutics, 23, 2017, 7, S. 590-604
Medientyp: E-Article
Sprache: Englisch
veröffentlicht:
Wiley
Schlagwörter:
Details
Zusammenfassung: <jats:title> <jats:bold>Summary</jats:bold> </jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Alzheimer's disease (<jats:styled-content style="fixed-case">AD</jats:styled-content>), a progressive development dementia, is increasingly impacting patients’ living conditions worldwide. Despite medical care and funding support, there are still no highly individualized drugs and practical strategies for clinical prevention and treatment. Developmentally regulated brain protein (abbreviated as Drebrin or Dbn, also known as Dbn1 in mouse) exists in neurons, especially in dendrites, and is an actin‐binding protein that modulates synaptic morphology and long‐term memory. However, the majority of previous studies have focused on its upstream proteins and neglected the impact Drebrin has on behavior and <jats:styled-content style="fixed-case">AD</jats:styled-content> in vivo.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Here, we tracked the behavioral performances of 4‐, 8‐, 12‐, and 16‐month‐old <jats:styled-content style="fixed-case">AD</jats:styled-content> mice and investigated the expression level of Drebrin in their hippocampi. A Pearson correlation analysis between Drebrin levels and behavioral data was performed. Subsequently, 2‐month‐old <jats:styled-content style="fixed-case">AD</jats:styled-content> mice were injected with <jats:styled-content style="fixed-case">rAAV</jats:styled-content>‐zsGreen‐Dbn1 vector, composing the <jats:styled-content style="fixed-case">APP</jats:styled-content>/<jats:styled-content style="fixed-case">PS</jats:styled-content>1‐Dbn1 group, and sex‐ and age‐matched <jats:styled-content style="fixed-case">AD</jats:styled-content> mice were injected with <jats:styled-content style="fixed-case">rAAV</jats:styled-content>‐tdTomato vector to serve as the control group. All mice were conducted behavioral tests and molecular detection 6 months later.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>(i) The expression of Drebrin is decreased in the hippocampus of aged <jats:styled-content style="fixed-case">AD</jats:styled-content> mice compared with that of age‐matched <jats:styled-content style="fixed-case">WT</jats:styled-content> and young adult <jats:styled-content style="fixed-case">AD</jats:styled-content> mice; (ii) cognitive ability of <jats:styled-content style="fixed-case">APP</jats:styled-content>/<jats:styled-content style="fixed-case">PS</jats:styled-content>1 mice decreases with age; (iii) Drebrin protein expression in the hippocampus correlates with behavioral performance in different aged <jats:styled-content style="fixed-case">AD</jats:styled-content> mice; (iv) cognitive ability improved significantly in <jats:styled-content style="fixed-case">APP</jats:styled-content>/<jats:styled-content style="fixed-case">PS</jats:styled-content>1‐Dbn1 mice; (v) the expression level of Drebrin in <jats:styled-content style="fixed-case">APP</jats:styled-content>/<jats:styled-content style="fixed-case">PS</jats:styled-content>1‐Dbn1 mouse hippocampus was significantly increased; (vi) the pathological lesion of <jats:styled-content style="fixed-case">AD</jats:styled-content> was alleviated in <jats:styled-content style="fixed-case">APP</jats:styled-content>/<jats:styled-content style="fixed-case">PS</jats:styled-content>1‐Dbn1 mice; (vii) the filamentous actin (F‐actin) and microtubule‐associated protein 2(<jats:styled-content style="fixed-case">MAP</jats:styled-content>‐2) in <jats:styled-content style="fixed-case">APP</jats:styled-content>/<jats:styled-content style="fixed-case">PS</jats:styled-content>1‐Dbn1 mice were notably more than control mice.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In this study, an effective expression of Drebrin improves cognitive abilities and alleviates lesions in an <jats:styled-content style="fixed-case">AD</jats:styled-content> mouse model. These results may provide some valid resources for therapy and research of <jats:styled-content style="fixed-case">AD</jats:styled-content>.</jats:p></jats:sec>
Umfang: 590-604
ISSN: 1755-5930
1755-5949
DOI: 10.1111/cns.12706