Evidence Details for Akt1
PMID Title Journal Year Abstract
37066940 Acupuncture improves learning and memory ability of posttraumatic stress disorder model rats through epigenetic regulation of microglial phosphatidylinositol 3-kinase pathway. Technol Health Care. 2023;31(S1):409-421. doi: 10.3233/THC-236035. 2023 BACKGROUND: Microglia express phosphatidylinositol 3-kinase (PI3K) has been implicated in the induction and maintenance of long-term potentiation (LTP) and in hippocampal synaptic plasticity. However, there are few studies on the interference of PI3K signal pathway in microglia. OBJECTIVE: The study goal is to gain a better understanding of the mechanism by which EA affects synapses provides insights into how electroacupuncture (EA) modulates synaptic plasticity in learning and memory. METHODS: Rat models of posttraumatic stress disorder (PTSD) were used to explore the effects of EA on microglial PI3K pathway, brain-derived neurotrophic factor (BDNF) and LTP, and the target and mechanism underlying the effects of EA on PI3K from the perspective of protein ubiquitination. RESULTS: EA induced microglial BDNF expression by activating the PI3K-AKT pathway, thereby facilitating LTP and synaptic plasticity. EA inhibited lincRNA 02023 to rescue the binding of WWP2 to PTEN, thereby promoting PTEN ubiquitination and degradation. CONCLUSION: The mechanism of EA improving the learning and memory ability of PTSD rats may be that it can promote the competitive combination of WWP2 and PTEN by inhibiting Linc RNA02023, and then lead to microglial PI3K and its pathway activation, BDNF up-regulation, and finally induce LTP and repair damaged synaptic plasticity."

Evidence Sentence: EA regulation of microglial expression of PI3K, AKT, CREB and BDNF
Evidence Sentence: The expression of PI3K, AKT, CREB and BDNF in microglia was confirmed by Western blotting.
Evidence Sentence: PI3K regulation of AKT and BDNF levels in microglia
Evidence Sentence: 2, the addition of active PI3K directly led to a significant increase in the levels of phosphorylated AKT ( 0.001) and total AKT ( 0.001) compared to the SPS group; this increase significantly upregulated BDNF expression ( 0.001).
Evidence Sentence: 4B, both the lincRNA 02023 overexpression (lincRNA 02023) group and the SPS group exhibited decreased ubiquitination of PTEN and decreased binding between PTEN and WWP2; these decreases rescued the expression of PI3K and AKT ( 0.01, Fig.
Evidence Sentence: These results suggest that EA increases the ubiquitination of PTEN (and thus promotes its degradation) by inhibiting the expression of lincRNA 02023; the lack of competition of lincRNA 02023 at the binding site of PTEN promotes the binding of WWP2 to PTEN, thereby upregulating the expression of PI3K and AKT ( 0.01, Fig.
Evidence Sentence: 1, compared with the blank control, the expression of PI3K ( 0.001), AKT ( 0.01), CREB ( 0.05) and BDNF ( 0.001) was significantly downregulated after SPS, indicating that the hippocampal microglial PI3K signalling pathway was inhibited in PTSD model rats.
Evidence Sentence: Upon EA treatment, microglial PI3K levels were significantly upregulated; in addition, the PI3K-dependent phosphorylation of AKT ( 0.01) and CREB ( 0.05) increased, and the total levels of AKT ( 0.001), CREB ( 0.001) and BDNF ( 0.01) increased as well, suggesting that the PI3K-AKT-CREB signalling pathway is activated by EA.
Evidence Sentence: The EA treatment described in this paper effectively improved the above symptoms; its underlying mechanism may be related to alterations of the PI3K-AKT signalling pathway and synaptic plasticity in the hippocampus .
Evidence Sentence: EA induced microglial BDNF expression by activating the PI3K-AKT pathway, thereby facilitating LTP and synaptic plasticity.
Evidence Sentence: Further investigation indicated that EA inhibited lincRNA 02023 and thus rescued the binding of WWP2 to PTEN, promoting PTEN ubiquitination and degradation to activate the PI3K-AKT pathway, which is a key factor in regulating LTP and restoring synaptic plasticity.
Evidence Sentence: Recent studies have shown that the PI3K-AKT-CREB pathway influences synaptic plasticity by regulating BDNF; therefore, we tested the effect of EA on LTP in PTSD rat models, in which the PI3K-AKT-CREB signalling pathway was compromised.
Evidence Sentence: EA restores synaptic plasticity of the hippocampal CA1 region by activating the PI3K-AKT-CREB signalling pathway in microglia
Evidence Sentence: As discussed above microglia express genes involved in neuronal synaptic plasticity, and PI3K and its associated PI3K-AKT-CREB signalling pathway play an important role in LTP.