ABSTRACT
Objective:
To evaluate the
role of
phosphatidylinositol 3-kinase (PI3K)/
serine threonine protein kinase (Akt)/mammalian
rapamycin target protein (mTOR) signaling pathway in
edaravone-induced reduction of
postoperative cognitive dysfunction in
aged rats.
Methods:
Sixty healthy
male Sprague-Dawley rats,
aged 20 months, weighing 600-700 g, were divided into 4 groups ( n=15 each) using a random number table
method:
control group (group C), operation group (group O),
edaravone group (group E) and PI3K inhibitor LY294002 group (group LY). The
rats received
laparotomy under 3%
sevoflurane anesthesia in O, E and LY groups.
Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and LY groups, and LY294002 0.3 mg/kg was simultaneously injected via the
tail vein in group LY.
Open field test was performed at 3 days after
surgery to evaluate the spontaneous activity of
rats, then
Morris water maze test was performed to evaluate the
cognitive function of
rats. The
rats were sacrificed after the end of behavioral experiment to isolate hippocampal
tissues for
determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR),
synaptophysin (SYP) and
postsynaptic density protein 95 (PSD 95) (by
Western blot ) and
dendrite length in hippocampal CA1 area (using Golgi
staining). The density of
dendrites was calculated.
Results:
There were no statistically significant differences in
exercise speed, distance, and
time of staying at the center between the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, the dendritic length of
neurons in
hippocampal CA1 region was shortened, and the density of
neurons in
hippocampal CA1 region was decreased in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was up-regulated, the dendritic length of
neurons in
hippocampal CA1 region was prolonged, and the density of
neurons in
hippocampal CA1 region was increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, and the dendritic length of
neurons in
hippocampal CA1 region was shortened, and the density of
neurons in
hippocampal CA1 region was decreased in group LY ( P<0.05).
Conclusions:
The mechanism by which
edaravone reduces
postoperative cognitive dysfunction is related to activating PI3K/Akt/mTOR signaling pathway and improving
synaptic plasticity in
aged rats.