THE NEUROPROTECTIVE EFFECT OF LITHIUM IN CANNABINOID DEPENDENCE IS MEDIATED THROUGH MODULATION OF CYCLIC AMP, ERK1/2 AND GSK-3B PHOSPHORYLATION IN CEREBELLAR GRANULAR NEURONS OF RAT

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RAHIMI HAMID REZA; GHAHREMANI MOHAMMAD HOSSEIN; DEHPOUR AHMAD REZA; SHARIFZADEH MOHAMMAD; EJTEMAEI MEHR SHAHRAM; RAZMI ALI; OSTADA SEYED NASSER

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Journal: Iranian Journal of Pharmaceutical Research Year:2015 | Volume:14 | Issue:4 Page(s): 1123-1135

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Title

THE NEUROPROTECTIVE EFFECT OF LITHIUM IN CANNABINOID DEPENDENCE IS MEDIATED THROUGH MODULATION OF CYCLIC AMP, ERK1/2 AND GSK-3B PHOSPHORYLATION IN CEREBELLAR GRANULAR NEURONS OF RAT

Author(s)

Keywords

DEPENDENCE

WIN 55

212-2

CEREBELLAR GRANULAR NEURONS

IN-VITRO

CYCLIC AMP

Abstract

thium (Li), a glycogen synthase kinase-3b (GSK-3b) inhibitor, has used to attenuate the cannabinoid-induced DEPENDENCE/withdrawal signs, but molecular mechanisms related to this are unclear. Recent studies indicate the involvement of upstream extracellular signal kinase1/2 (ERK1/2) and downstream GSK-3b pathways in the development of cannabinoid-induced DEPENDENCE. This is mediated through cannabinoid receptor 1 (CB1) enriched in CEREBELLAR GRANULAR NEURONS (CGNs). Accordingly, the present study aimed to investigate the mechanism of modulatory/neuroprotective effects of Li on a cannabinoid agonist (WIN 55,212-2 (WIN))-induced DEPENDENCE, through quantitative analysis of some involved proteins such as ERK1/2, GSK-3b and related signaling pathways including their phosphorylated forms; and cAMP level as the other molecular mechanisms leading to DEPENDENCE, in CGNs model. The CGNs were prepared from 7-day-old Wistar rat pup in a 12-well plate, pretreated with Li (1mM) and an ERK1/2 inhibitor SL327 (SL, 10 mM). The WIN (1 mM) was added 30 minutes prior to treatment and AM251 (AM, 1 mM), as a cannabinoid antagonist was co-treated with WIN. The cAMP level, as an indicator of cannabinoid-induced DEPENDENCE, was measured by ELISA following forskolin (FSK) stimulation. Western blot analyses determined the phosphorylated forms of ERK1/2 (p-ERK1/2), GSK-3b (p-GSK-3b) as well as their total expressions in various treatment times and doses in CGNs. WIN alone could down regulate the cAMP/p-ERK1/2 cascade compared to AM treatment. However, P-GSK-3b was up-regulated with Li and WIN or with SL and Li pretreatment to AM-induced cellular response, which was the highest 60 minutes after CGNs exposure. Results further suggested the potential role of Li pretreatment to diminish the development of cannabinoid-induced DEPENDENCE/neuronal injury through possible mechanisms of modulating the cAMP/p-ERK1/2 cascade independent of p-GSK-3b signaling pathway IN-VITRO.

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APA: Copy

RAHIMI, HAMID REZA, GHAHREMANI, MOHAMMAD HOSSEIN, DEHPOUR, AHMAD REZA, SHARIFZADEH, MOHAMMAD, EJTEMAEI MEHR, SHAHRAM, RAZMI, ALI, & OSTADA, SEYED NASSER. (2015). THE NEUROPROTECTIVE EFFECT OF LITHIUM IN CANNABINOID DEPENDENCE IS MEDIATED THROUGH MODULATION OF CYCLIC AMP, ERK1/2 AND GSK-3B PHOSPHORYLATION IN CEREBELLAR GRANULAR NEURONS OF RAT. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 14(4), 1123-1135. SID. https://sid.ir/paper/288373/en

Vancouver: Copy

RAHIMI HAMID REZA, GHAHREMANI MOHAMMAD HOSSEIN, DEHPOUR AHMAD REZA, SHARIFZADEH MOHAMMAD, EJTEMAEI MEHR SHAHRAM, RAZMI ALI, OSTADA SEYED NASSER. THE NEUROPROTECTIVE EFFECT OF LITHIUM IN CANNABINOID DEPENDENCE IS MEDIATED THROUGH MODULATION OF CYCLIC AMP, ERK1/2 AND GSK-3B PHOSPHORYLATION IN CEREBELLAR GRANULAR NEURONS OF RAT. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2015;14(4):1123-1135. Available from: https://sid.ir/paper/288373/en

IEEE: Copy

HAMID REZA RAHIMI, MOHAMMAD HOSSEIN GHAHREMANI, AHMAD REZA DEHPOUR, MOHAMMAD SHARIFZADEH, SHAHRAM EJTEMAEI MEHR, ALI RAZMI, and SEYED NASSER OSTADA, “THE NEUROPROTECTIVE EFFECT OF LITHIUM IN CANNABINOID DEPENDENCE IS MEDIATED THROUGH MODULATION OF CYCLIC AMP, ERK1/2 AND GSK-3B PHOSPHORYLATION IN CEREBELLAR GRANULAR NEURONS OF RAT,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 14, no. 4, pp. 1123–1135, 2015, [Online]. Available: https://sid.ir/paper/288373/en

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