| Title |
Stimulation of ACE2/ANG(1–7)/Mas Axis by Diminazene Ameliorates Alzheimer’s Disease in the D-Galactose-Ovariectomized Rat Model: Role of PI3K/Akt Pathway
|
|---|---|
| Published in |
Molecular Neurobiology, March 2018
|
| DOI | 10.1007/s12035-018-0966-3 |
| Pubmed ID | |
| Authors |
Ahmed S. Kamel, Noha F. Abdelkader, Sahar S. Abd El-Rahman, Marwan Emara, Hala F. Zaki, Mahmoud M. Khattab |
| Abstract |
Overactivation of angiotensin-converting enzyme/angiotensin 2/angiotensin receptor-1 (ACE/Ang2/AT1) axis provokes amyloid-β-induced apoptosis and neurodegeneration in Alzheimer's disease (AD). Moreover, activation of AT1 impairs the survival pathway phosphoinositide 3-kinase/protein kinase B (PI3K/Akt). Interestingly, the coupling between ACE2/Ang(1-7)/Mas receptor (MasR) axis and PI3K/Akt activation opposes AT1-induced apoptosis. However, the effect of in vivo stimulation of MasR against AD and its correlation to PI3K/Akt is not yet elucidated. Thus, the present study aimed to investigate the relationship between PI3K/Akt pathway and the activation of ACE2/MasR in the AD model of D-galactose-ovariectomized rats. AD features were induced following 8-week injection of D-galactose (150 mg/kg, i.p.) in ovariectomized female rats. The ACE2 activator dimenazine (15 mg/kg, i.p.) was daily administered for 2 months. DIZE administration boosted the hippocampal expression of ACE2 and Mas receptors while suppressing AT1 receptor. Notably, dimenazine enhanced the expression of phosphorylated survival factors (PI3K, Akt, signal transducer, and activator of transcription-3) and neuroplasticity proteins such as cyclic adenosine monophosphate-responsive element-binding protein and brain-derived neurotrophic factor along with nicotinic and glutamatergic receptors. Such effects were accompanied by suppressing phosphorylated tau and glycogen synthase kinase3β along with caspase-3, cytochrome-c, nuclear factor kappa B, tumor necrosis factor alpha, and glial fibrillary acidic protein contents. Dimenazine ameliorated the histopathological damage observed in D-galactose-ovariectomized rats and improved their learning and recognition memory in Morris water maze and novel object recognition tests. In conclusion, dimenazine-induced stimulation of ACE2/Ang(1-7)/Mas axis subdues cognitive deficits in AD most probably through activation of PI3K/Akt pathway. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 86 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 86 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 14 | 16% |
| Student > Ph. D. Student | 11 | 13% |
| Student > Master | 11 | 13% |
| Professor | 4 | 5% |
| Student > Bachelor | 4 | 5% |
| Other | 12 | 14% |
| Unknown | 30 | 35% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 14 | 16% |
| Biochemistry, Genetics and Molecular Biology | 8 | 9% |
| Medicine and Dentistry | 6 | 7% |
| Neuroscience | 5 | 6% |
| Immunology and Microbiology | 4 | 5% |
| Other | 13 | 15% |
| Unknown | 36 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 March 2018.
All research outputs
#3,157,402
of 23,026,672 outputs
Outputs from Molecular Neurobiology
#606
of 3,488 outputs
Outputs of similar age
#67,360
of 332,611 outputs
Outputs of similar age from Molecular Neurobiology
#19
of 137 outputs
Altmetric has tracked 23,026,672 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,488 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done well, scoring higher than 80% of its peers.
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We're also able to compare this research output to 137 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.