دورية أكاديمية
RNA interference-mediated knockdown of long-form phosphodiesterase-4D (PDE4D) enzyme reverses amyloid-β42-induced memory deficits in mice.
| العنوان: | RNA interference-mediated knockdown of long-form phosphodiesterase-4D (PDE4D) enzyme reverses amyloid-β42-induced memory deficits in mice. |
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| المؤلفون: | Zhang C; Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology, West Virginia University Health Sciences Center, Morgantown, WV, USA., Cheng Y, Wang H, Wang C, Wilson SP, Xu J, Zhang HT |
| المصدر: | Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2014; Vol. 38 (2), pp. 269-80. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: IOS Press Country of Publication: Netherlands NLM ID: 9814863 Publication Model: Print Cited Medium: Internet ISSN: 1875-8908 (Electronic) Linking ISSN: 13872877 NLM ISO Abbreviation: J Alzheimers Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; Washington : IOS Press, c1998- |
| مواضيع طبية MeSH: | Memory Disorders*/chemically induced , Memory Disorders*/enzymology , Memory Disorders*/therapy, Amyloid beta-Peptides/*pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 4/*deficiency , Gene Expression Regulation/*physiology , Peptide Fragments/*pharmacology , RNA Interference/*physiology, Animals ; Cyclic AMP/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics ; Disease Models, Animal ; Exploratory Behavior/drug effects ; Exploratory Behavior/physiology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/genetics ; Hippocampus/drug effects ; Hippocampus/metabolism ; Male ; Maze Learning/drug effects ; Maze Learning/physiology ; Mice ; Mice, Inbred ICR ; Reaction Time/drug effects ; Reaction Time/genetics ; Recognition, Psychology/drug effects ; Recognition, Psychology/physiology |
| مستخلص: | Phosphodiesterase-4 (PDE4) inhibitors enhance memory, increase hippocampal neurogenesis, and reverse amyloid-β (Aβ)-induced memory deficits. Here, we examined whether long-form PDE4D knockdown by lentiviral RNA construct containing a specific microRNA/miRNA-mir hairpin structure (4DmiRNA) reversed memory impairment caused by amyloid-β1-42 (Aβ42) in mice using the Morris water maze (MWM) and novelty object recognition tests. Western blotting analysis was used to assess protein levels of cAMP response element-binding protein (CREB, unphosphorylated and phosphorylated [pCREB]), brain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB) to explore the neurochemical mechanisms. Aggregated Aβ42 (0.5 μg/side) bilaterally infused in dentate gyrus decreased cAMP levels (p < 0.01) and produced memory deficits in the MWM (p < 0.01) and object recognition tests (p < 0.01). Microinfusions of lentiviruses resulted in downregulated expression of PDE4D4 and 4D5 proteins and reversed Aβ42-induced cAMP decline (p < 0.05) and memory deficits. Treatment also concomitantly increased pCREB (p < 0.05) and BDNF (p < 0.01) and reduced IL-1β (p < 0.05), TNF-α (p < 0.01), and NF-κB (p65) (p < 0.05) in the hippocampus of Aβ42-challenged mice. These results suggest that long-form PDE4D knockdown may offer a promising treatment for memory loss associated with Alzheimer's disease. |
| معلومات مُعتمدة: | AG031687 United States AG NIA NIH HHS |
| فهرسة مساهمة: | Keywords: Alzheimer's disease; PDE4; anti-inflammation; long-form PDE4D; memory |
| المشرفين على المادة: | 0 (Amyloid beta-Peptides) 0 (Peptide Fragments) 0 (amyloid beta-protein (1-42)) E0399OZS9N (Cyclic AMP) EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4) EC 3.1.4.17 (PDE4D protein, mouse) |
| تواريخ الأحداث: | Date Created: 20130817 Date Completed: 20140627 Latest Revision: 20220408 |
| رمز التحديث: | 20221213 |
| DOI: | 10.3233/JAD-122236 |
| PMID: | 23948935 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1875-8908 |
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| DOI: | 10.3233/JAD-122236 |