AKT Signaling Pathway in the Nucleus Accumbens Mediates Excessive Alcohol Drinking Behaviors

Abstract Background: Nucleus accumbens (NAc) inflammation is implicated in the development and progression of depression but the underlying mechanism remains largely unclear. We previously reported that dopamine D3 receptor (D3R) expressed in the NAc strongly correlated with inflammation-related depression. The objective of the present study is to determine the exact mechanism of D3R in the NAc inflammation relevant depression.Methods: Bilateral NAc injection of Lipopolysaccharide (LPS)-induced NAc inflammation mouse model was used to explore the relationship between NAc inflammation and depressive-like behaviors. Either conditional knockout of D3R in the NAc in the adult mice or restoration of D3R expression in the NAc in D3R mutant mice was applied to investigate the effects of D3R in the NAc on depressive disorders. The exact molecular mechanism of D3R in the NAc inflammation-induced depressive-like phenotype was ascertained by in vivo and in vitro studies. Results: NAc inflammation induced by intra-NAc LPS triggered a series of depressive-like disorders, and the interaction of D3R and microglia activation involved in the NAc inflammation-induced depressive-like phenotype. We observed that selective knock-down of D3R in the NAc elicited the depressive-like behaviors, but re-expression of D3R in the NAc alleviated the depressive-like behaviors established by D3R mutation. Finally, D3R in the NAc mediated microglial polarization to M1 phenotype mainly through Akt signaling pathway. Conclusions: These findings provide direct evidence that not only NAc inflammation but also down-regulation of D3R in the NAc has a role in regulation the initiation and development of depression, and indicate that D3R negatively regulated microglial M1 polarization mainly via Akt signaling pathway that may be involved in the NAc inflammation and thereby depressive-like behaviors.

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Phentermine induces conditioned rewarding effects via activation of the PI3K/Akt signaling pathway in the nucleus accumbens

Psychopharmacology ◽

10.1007/s00213-016-4231-z ◽

2016 ◽

Vol 233 (8) ◽

pp. 1405-1413 ◽

Cited By ~ 4

Author(s):

Sa-Ik Hong ◽

Min-Jung Kim ◽

In-Jee You ◽

Seung-Hwan Kwon ◽

Shi-Xun Ma ◽

...

Keyword(s):

Nucleus Accumbens ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway

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Faculty Opinions recommendation of mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726205255.793516013 ◽

2016 ◽

Author(s):

Yavin Shaham ◽

Xuan (Anna) Li

Keyword(s):

Alcohol Drinking ◽

Collapsin Response Mediator Protein ◽

Mediator Protein ◽

Excessive Alcohol ◽

Drinking Behaviors

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Faculty Opinions recommendation of Rpn10 promotes tumor progression by regulating hypoxia-inducible factor 1 alpha through the PTEN/Akt signaling pathway in hepatocellular carcinoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734911165.793580826 ◽

2020 ◽

Author(s):

Leonardo Salmena

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Progression ◽

Signaling Pathway ◽

Hypoxia Inducible Factor ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Hypoxia Inducible Factor 1

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Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20110511 ◽

2011 ◽

Vol 9 (5) ◽

pp. 533-538 ◽

Cited By ~ 9

Author(s):

ZH Chu

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Phosphatidylinositol 3 Kinase ◽

Proliferation And Apoptosis ◽

Mcf 7 ◽

Phosphatidylinositol 3

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Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666201005143818 ◽

2020 ◽

Vol 20 ◽

Author(s):

Md. Junaid ◽

Yeasmin Akter ◽

Syeda Samira Afrose ◽

Mousumi Tania ◽

Md. Asaduzzaman Khan

Keyword(s):

Clinical Trials ◽

Signaling Pathways ◽

Signaling Pathway ◽

Inhibitory Effect ◽

Akt Signaling ◽

Review Article ◽

Therapeutic Drug ◽

Akt Signaling Pathway ◽

Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

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PI3K/Akt Signaling Pathway Ameliorates Oxidative Stress-Induced Apoptosis upon Manganese Exposure in PC12 Cells

Biological Trace Element Research ◽

10.1007/s12011-021-02687-1 ◽

2021 ◽

Author(s):

Yanli Tan ◽

Hong Cheng ◽

Cheng Su ◽

Pan Chen ◽

Xiaobo Yang

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Pc12 Cells ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Manganese Exposure ◽

Induced Apoptosis

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Retraction: Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signaling pathway in IL-1β-induced osteoarthritis chondrocytes

RSC Advances ◽

10.1039/d1ra90026a ◽

2021 ◽

Vol 11 (8) ◽

pp. 4441-4441

Author(s):

Laura Fisher

Keyword(s):

Inflammatory Response ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Akt Signaling ◽

Salvianolic Acid B ◽

Signalling Pathway ◽

Akt Signaling Pathway ◽

Salvianolic Acid ◽

Osteoarthritis Chondrocytes

Retraction of ‘Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signalling pathway in IL-1β-induced osteoarthritis chondrocytes’ by Bin Zhu et al., RSC Adv., 2018, 8, 36422–36429, DOI: 10.1039/C8RA02418A.

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