Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis

Hill, Jeremy; Zuluaga-Ramirez, Viviana; Gajghate, Sachin; Winfield, Malika; Persidsky, Yuri

doi:10.1111/bph.14387

Cited by 31 publications

(29 citation statements)

References 63 publications

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“…According to previous unbiased stereology protocol (Hill et al, 2018), every sixth section throughout the entire rostral caudal extent of the hippocampus was used to determine the number of BrdU-labeled cells or DCX + in the DG. The number of BrdU+ or DCX+ cells was counted under a fluorescence microscope (Olympus, Japan) in the area of the subgranular zone (SGZ).…”

Section: Methodsmentioning

confidence: 99%

Electroacupuncture Pretreatment Ameliorates PTSD-Like Behaviors in Rats by Enhancing Hippocampal Neurogenesis via the Keap1/Nrf2 Antioxidant Signaling Pathway

Zhou

Xue

et al. 2019

Front. Cell. Neurosci.

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Electroacupuncture (EA) pretreatment is a clinically useful therapy for several brain disorders. However, whether and via which exact molecular mechanisms it ameliorates post-traumatic stress disorder (PTSD) remains unclear. In the present study, rats received EA stimulation for seven consecutive days before exposure to enhanced single prolonged stress (ESPS). Anxiety-like and fear learning behaviors; hippocampal neurogenesis; the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (keap1), and heme oxygenase 1 (HO-1); and the activity of AMP-activated kinase (AMPK) were evaluated at 14 days after ESPS. EA pretreatment improved hippocampal neurogenesis and ameliorated anxiety-like behaviors in ESPS-treated rats. EA pretreatment also increased the expression of Nrf2 and HO-1 and the activity of AMPK. Furthermore, Nrf2 knockdown by a short hairpin RNA affected anxiety-like behaviors and expression of neuroprotective markers (BDNF, DCX) in a manner similar to ESPS alone and dampened the neuroprotective effects of EA pretreatment. In contrast, Keap1 knockdown increased the expression of HO-1, improved hippocampal neurogenesis, and alleviated PTSD-like behaviors. Altogether, our results suggest that EA pretreatment ameliorates ESPS-induced anxiety-like behaviors and prevents hippocampal neurogenesis disruption in a rat model of PTSD possibly through regulation of the keap1/Nrf2 antioxidant defense pathway.

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Section: Methodsmentioning

confidence: 99%

Electroacupuncture Pretreatment Ameliorates PTSD-Like Behaviors in Rats by Enhancing Hippocampal Neurogenesis via the Keap1/Nrf2 Antioxidant Signaling Pathway

Zhou

Xue

et al. 2019

Front. Cell. Neurosci.

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“…CB1, CB2, and GPR55 take part in the regulation of neurogenesis. CB1 and GPR55 are crucial for proliferation and differentiation of neural stem cells (NSCs) [162][163][164]. Additionally, CB1 and CB2 control the development of astrocytes [165].…”

Section: Neurodegenerationmentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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“…Our in vivo experiments conducted in STK40 -/- mice further confirmed these results, as substantiated by the diminished number of cells positive for Ki67, BrdU, Lef1, Gata-3, and AE13, with an increase in the proportion of cleaved caspase 3-positive cells. Ki67 was considered as a viable marker for cell proliferation, and BrdU staining has been adopted for the identification of surviving and proliferating cells [ 18 ]. Transcription factor Lef1 serves as an essential biomarker for HF-derived neural crest stem cells melanocytic differentiation [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

EZH2-mediated inhibition of microRNA-22 promotes differentiation of hair follicle stem cells by elevating STK40 expression

Cai

Zheng

et al. 2020

Aging

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Hair follicle stem cells (HFSCs) contribute to the regeneration of hair follicles (HFs), thus accelerating hair growth. microRNAs (miRs) are potential regulators in various cellular processes, including HFSC proliferation and differentiation. This study proposed a potential target, enhancer of zeste homolog 2 (EZH2) for facilitating hair growth, due to its function over HFSC activities by mediating the miR-22/serine/threonine kinase 40 (STK40)/myocyte enhancer factor 2 (MEF2)/alkaline phosphatase (ALP) axis. Gain- and loss-of-function approaches were adopted to explore the roles of EZH2, miR-22, and STK40 in the proliferation and apoptosis of HFSCs, along with the functional relevance of MEF2-ALP activity. STK40 was elevated during HFSC differentiation, which was found to facilitate HFSC proliferation, but impede their apoptosis by activating MEF2-ALP. Mechanically, miR-22 targeted and inversely regulated STK40, which inhibited MEF2-ALP activity to impede HFSC proliferation and differentiation. Moreover, EZH2 elevated the STK40 expression by repressing miR-22 to promote the proliferation and differentiation of HFSCs. Furthermore, in vivo experiments further validated the roles of EZH2 and STK40 on hair follicle neogenesis and hair growth. Collectively, EZH2 elevated the STK40 expression by downregulating miR-22, consequently accelerating differentiation of HFSCs and hair growth, which sheds light on the underlying molecular mechanism responsible for hair growth.

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Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis

Abstract: Together, these findings suggest GPR55 activation as a novel target and strategy to regulate NSC proliferation and adult neurogenesis.

Cited by 31 publications

References 63 publications

Electroacupuncture Pretreatment Ameliorates PTSD-Like Behaviors in Rats by Enhancing Hippocampal Neurogenesis via the Keap1/Nrf2 Antioxidant Signaling Pathway

Electroacupuncture Pretreatment Ameliorates PTSD-Like Behaviors in Rats by Enhancing Hippocampal Neurogenesis via the Keap1/Nrf2 Antioxidant Signaling Pathway

A Guide to Targeting the Endocannabinoid System in Drug Design

EZH2-mediated inhibition of microRNA-22 promotes differentiation of hair follicle stem cells by elevating STK40 expression

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