Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists

Pascual, Ana Clara; Martín‐Moreno, Ana M.; Giusto, Norma M.; Ceballos, Marı́a L. de; Pasquaré, Susana J.

doi:10.1016/j.exger.2014.10.011

Cited by 37 publications

(33 citation statements)

References 64 publications

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“…However, animal studies reported either no effect 13,14 or an age-related increase 13,15 in FAAH activity or protein and we did not observe a significant effect of age on In conclusion, we show for the first time that FAAH activity in brain is dependent on a common gene variant and that genotyping for FAAH rs324420 variants during [ 11 C]CURB/PET will allow better interpretation of data.…”

Section: Discussioncontrasting

confidence: 48%

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

Boileau

Tyndale

Williams

et al. 2015

J Cereb Blood Flow Metab

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The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant phenotype and risk for addictions. Here, we tested whether the FAAH polymorphism affects in vivo binding of the FAAH positron emission tomography (PET) probe [11 C]CURB ([ 11 C-carbonyl]-6-hydroxy-[1,10-biphenyl]-3-yl cyclohexylcarbamate (URB694)). Participants (n = 24) completed one [ 11 C]CURB/PET scan and were genotyped for rs324420. Relative to C/C (58%), A-allele carriers (42%) had 23% lower [11 C]CURB binding (λk 3 ) in brain. We report evidence that the genetic variant rs324420 in FAAH is associated with measurable differences in brain FAAH binding as per PET [ 11 C]CURB measurement.

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Section: Discussioncontrasting

confidence: 48%

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

Boileau

Tyndale

Williams

et al. 2015

J Cereb Blood Flow Metab

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“…CB1 receptor was regarded as CNS-protecting protein in a series of neuropathy. 39,40 Recently, increasing studies reported that the activation of CB1 receptor protects against hippocampal senescence [22][23][24] and that chronic low dose of ∆9-tetrahydrocannabinol (THC) improve cognitive disorder by restoration of CB1 signalling in old mice. 41 Therefore, we speculated that CB1 receptor may be a possible mediator of In conclusion, the present study elucidated that Spd is not only able to overcome HG-induced neurotoxicity and senescence but also prevent HG-induced downregulation of CB1 receptor expression in HT-22 cells.…”

Section: Discussionmentioning

confidence: 99%

“…It has been found that the expression of CB1 receptor is decreased in the brain of aged animals and that the cortexes of Alzheimer disease (AD) patients display lower CB1 receptor expression levels, compare to age‐matched people . In addition, it has been confirmed that the agonist of CB1 receptor attenuates aging‐induced hippocampal neuroinflammation and neurogenesis decline and the pathological aging in human Alzheimer's disease . In contrast, loss of CB1 receptor results in accelerated lipofuscin accumulation in the hippocampus .…”

Section: Introductionmentioning

confidence: 98%

“…21 In addition, it has been confirmed that the agonist of CB1 receptor attenuates aging-induced hippocampal neuroinflammation and neurogenesis decline 22 and the pathological aging in human Alzheimer's disease. 23 In contrast, loss of CB1 receptor results in accelerated lipofuscin accumulation in the hippocampus. 24 These previous studies have provided important evidence that CB1 receptor may delay the senescence process in brain.…”

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confidence: 99%

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Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Zhu

Fan

Tang

et al. 2018

Clin Exp Pharma Physio

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Hyperglycaemia-induced neurotoxicity involved in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglyceamic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti-aging function in many tissues. However, the role of Spd in hyperglyceamia-induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)-treated HT-22 cell as vitro model to investigate whether Spd protects neurons against hyperglyceamia-induced senescence and the mediatory role of CB1 receptor. The HT-22 cells were cultured in HG condition in the presence of different dose of Spd. Then, the viability of cells was measured by Cell Counting Kit-8 (CCK-8) assay. The senescence of cells was detected by Senescence-associated β-galactosidase (SA-β-Gal) staining. The expressions of p16 , p21 and CB1 receptor were measured by western blot. We found that Spd inhibited HG-induced neurotoxicity (the loss of cell viability) and senescence (the increase of SA-β-Gal positive cells, the upregulation of p16 and p21 ) in HT-22 cells. Also, Spd prevented HG-induced downregulation of CB1 receptor in HT-22 cells. Furthermore, we demonstrated that AM251 (a specific inhibitor of the CB1 receptor) reversed the protective effects of Spd on HG-induced neurotoxicity and senescence. These results indicated that Spd prevents HG-induced neurotoxicity and senescence via the upregulation of CB1 receptor. Our findings provide a promising future of Spd-based preventions and therapies for diabetic encephalopathy.

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“…) and decreased FAAH activity in cortical membrane tissues of AD patients (Pascual et al . ). Other studies have reported increased DAG lipase alpha (DAGLα) in the hippocampus of AD patients (Farooqui et al .…”

Section: Changes In the Endocannabinoid System In Neurodegenerative Dmentioning

confidence: 97%

Endocannabinoid system in neurodegenerative disorders

Basavarajappa

Shivakumar

Joshi

et al. 2017

Journal of Neurochemistry

168

140

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Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid (EC) system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs.

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Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists

Cited by 37 publications

References 64 publications

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Endocannabinoid system in neurodegenerative disorders

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Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists

Cited by 37 publications

References 64 publications

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [11C]CURB

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [11C]CURB

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Endocannabinoid system in neurodegenerative disorders

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The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB