| Title |
Neuroprotection Through Rapamycin-Induced Activation of Autophagy and PI3K/Akt1/mTOR/CREB Signaling Against Amyloid-β-Induced Oxidative Stress, Synaptic/Neurotransmission Dysfunction, and Neurodegeneration in Adult Rats
|
|---|---|
| Published in |
Molecular Neurobiology, September 2016
|
| DOI | 10.1007/s12035-016-0129-3 |
| Pubmed ID | |
| Authors |
Abhishek Kumar Singh, Mahendra Pratap Kashyap, Vinay Kumar Tripathi, Sandeep Singh, Geetika Garg, Syed Ibrahim Rizvi |
| Abstract |
Autophagy is a catabolic process involved in the continuous removal of toxic protein aggregates and cellular organelles to maintain the homeostasis and functional integrity of cells. The mechanistic understanding of autophagy mediated neuroprotection during the development of neurodegenerative disorders remains elusive. Here, we investigated the potential role of rapamycin-induced activation of autophagy and PI3K/Akt1/mTOR/CREB pathway(s) in the neuroprotection of amyloid-beta (Aβ1-42)-insulted hippocampal neurons in rat model of Alzheimer's disease (AD) like phenotypes. A single intra-hippocampal injection of Aβ1-42 impaired redox balance and markedly induced synaptic dysfunction, neurotransmission dysfunction, and cognitive deficit, and suppressed pro-survival signaling in the adult rats. Rapamycin administration caused a significant reduction of mTOR complex 1 phosphorylation at Ser2481 and a significant increase in levels of autophagy markers such as microtubule-associated protein-1 light chain-3 (LC3), beclin-1, sequestosome-1/p62, unc-51-like kinase 1 (ULK1). In addition, rapamycin induced the activation of autophagy that further activated p-PI3K, p-Akt1 (Ser473), and p-CREB (Ser183) expression in Aβ1-42-treated rats. The activated autophagy markedly reversed Aβ1-42-induced impaired redox homeostasis by decreasing the levels of prooxidants-ROS generation, intracellular Ca(2+) flux and LPO, and increasing the levels of antioxidants-SOD, catalase, and GSH. The activated autophagy also provided significant neuroprotection against Aβ1-42-induced synaptic dysfunction by increasing the expression of synapsin-I, synaptophysin, and PSD95; and neurotransmission dysfunction by increasing the levels of CHRM2, DAD2 receptor, NMDA receptor, and AMPA receptor; and ultimately improved cognitive ability in rats. Wortmannin administration significantly reduced the expression of autophagy markers, p-PI3K, p-Akt1, and p-CREB, as well as the autophagy mediated neuroprotective effect. Our study demonstrate that autophagy can be an integrated part of pro-survival (PI3K/Akt1/mTOR/CREB) signaling and autophagic activation restores the oxidative defense mechanism(s), neurodegenerative damages, and maintains the integrity of synapse and neurotransmission in rat model of AD. |
X Demographics
The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 13% |
| Unknown | 7 | 88% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 63% |
| Scientists | 2 | 25% |
| Practitioners (doctors, other healthcare professionals) | 1 | 13% |
Mendeley readers
The data shown below were compiled from readership statistics for 101 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | <1% |
| Unknown | 100 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 17 | 17% |
| Student > Bachelor | 15 | 15% |
| Researcher | 9 | 9% |
| Student > Doctoral Student | 6 | 6% |
| Student > Master | 6 | 6% |
| Other | 14 | 14% |
| Unknown | 34 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 14 | 14% |
| Biochemistry, Genetics and Molecular Biology | 12 | 12% |
| Agricultural and Biological Sciences | 10 | 10% |
| Medicine and Dentistry | 10 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 7% |
| Other | 8 | 8% |
| Unknown | 40 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 14. 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 25 March 2023.
All research outputs
#2,599,709
of 25,554,853 outputs
Outputs from Molecular Neurobiology
#277
of 3,989 outputs
Outputs of similar age
#42,623
of 329,127 outputs
Outputs of similar age from Molecular Neurobiology
#12
of 129 outputs
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