| Title |
Metformin improves anxiety-like behaviors through AMPK-dependent regulation of autophagy following transient forebrain ischemia
|
|---|---|
| Published in |
Metabolic Brain Disease, May 2015
|
| DOI | 10.1007/s11011-015-9677-x |
| Pubmed ID | |
| Authors |
Alireza Sarkaki, Yaghoob Farbood, Mohammad Badavi, Leila Khalaj, Fariba Khodagholi, Ghorbangol Ashabi |
| Abstract |
Stroke is one of the main threats to the public health worldwide. Metformin, an anti-diabetic drug, is an activator of AMP-activated protein kinase (AMPK). Metformin plays an important role on improving behavior in neurodegenerative diseases through diverse pathways. In the current study we aimed to investigate the probable effects of metformin on anxiety and autophagy pathway in global cerebral ischemia. Rats were divided into seven groups; Sham, ischemia (I/R), metformin (met), compound c (CC), CC+ischemia, met+ischemia, met+CC+ischemia. Metformin was pretreated for 2 weeks and CC administrated half an hour before global cerebral ischemia. Blood glucose, body weight, sensorimotor scores, elevated plus maze and open field test were evaluated after ischemia. Autophagy related factors were measured by Western blot and immunofluorescent assay in hippocampus of rats. Based on our results, pretreatment of rats by metformin improved sensory motor signs, anxiolytic behavior and locomotion in ischemic rats. CC injection in I/R rats attenuated the therapeutic effects of metformin. Autophagy factors such as light chain 3B, Atg7, Atg5-12 and beclin-1 decreased in ischemic rats compared to the sham group (P < 0.001 in all proteins). Level of autophagic factors increased in metformin pretreated rats compared to global cerebral ischemia (P < 0.001 in all proteins). These data indicated that the beneficial role of metformin in behavior and autophagy flux mediates via AMPK. Our results recommended that metformin therapy could improve psychological disorders and movement disability following I/R and profound understanding of AMPK-dependent autophagy would enhance its development as a promising target for intracellular pathway. |
X Demographics
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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 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 56 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 13% |
| Researcher | 7 | 13% |
| Student > Bachelor | 7 | 13% |
| Student > Master | 6 | 11% |
| Student > Doctoral Student | 4 | 7% |
| Other | 12 | 21% |
| Unknown | 13 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 18% |
| Neuroscience | 8 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 9% |
| Agricultural and Biological Sciences | 5 | 9% |
| Biochemistry, Genetics and Molecular Biology | 3 | 5% |
| Other | 6 | 11% |
| Unknown | 19 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 06 May 2015.
All research outputs
#20,273,512
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Outputs from Metabolic Brain Disease
#834
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Outputs of similar age
#222,670
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Outputs of similar age from Metabolic Brain Disease
#16
of 21 outputs
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