PMID- 23948935
OWN - NLM
STAT- MEDLINE
DCOM- 20140627
LR  - 20220408
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 38
IP  - 2
DP  - 2014
TI  - RNA interference-mediated knockdown of long-form phosphodiesterase-4D (PDE4D) 
      enzyme reverses amyloid-beta42-induced memory deficits in mice.
PG  - 269-80
LID - 10.3233/JAD-122236 [doi]
AB  - Phosphodiesterase-4 (PDE4) inhibitors enhance memory, increase hippocampal 
      neurogenesis, and reverse amyloid-beta (Abeta)-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-beta1-42 (Abeta42) 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-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and nuclear 
      factor-kappaB (NF-kappaB) to explore the neurochemical mechanisms. Aggregated Abeta42 (0.5 
      mug/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 Abeta42-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-1beta (p < 0.05), TNF-alpha (p < 0.01), and NF-kappaB (p65) (p < 
      0.05) in the hippocampus of Abeta42-challenged mice. These results suggest that 
      long-form PDE4D knockdown may offer a promising treatment for memory loss 
      associated with Alzheimer's disease.
FAU - Zhang, Cong
AU  - Zhang C
AD  - 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.
FAU - Cheng, Yufang
AU  - Cheng Y
FAU - Wang, Haitao
AU  - Wang H
FAU - Wang, Chuang
AU  - Wang C
FAU - Wilson, Steven P
AU  - Wilson SP
FAU - Xu, Jiangping
AU  - Xu J
FAU - Zhang, Han-Ting
AU  - Zhang HT
LA  - eng
GR  - AG031687/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - EC 3.1.4.17 (PDE4D protein, mouse)
SB  - IM
MH  - Amyloid beta-Peptides/*pharmacology
MH  - Animals
MH  - Cyclic AMP/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4/*deficiency/genetics
MH  - Disease Models, Animal
MH  - Exploratory Behavior/drug effects/physiology
MH  - Gene Expression Regulation/drug effects/genetics/*physiology
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - *Memory Disorders/chemically induced/enzymology/therapy
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Peptide Fragments/*pharmacology
MH  - RNA Interference/*physiology
MH  - Reaction Time/drug effects/genetics
MH  - Recognition, Psychology/drug effects/physiology
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - PDE4
OT  - anti-inflammation
OT  - long-form PDE4D
OT  - memory
EDAT- 2013/08/21 06:00
MHDA- 2014/06/28 06:00
CRDT- 2013/08/17 06:00
PHST- 2013/08/17 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/06/28 06:00 [medline]
AID - E2K120L7840414NM [pii]
AID - 10.3233/JAD-122236 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2014;38(2):269-80. doi: 10.3233/JAD-122236.