scholarly journals Lack of Cannabinoid Receptor Type-1 Leads to Enhanced Age-Related Neuronal Loss in the Locus Coeruleus

2020 ◽  
Vol 22 (1) ◽  
pp. 5
Author(s):  
Alessandra Gargano ◽  
Eva Beins ◽  
Andreas Zimmer ◽  
Andras Bilkei-Gorzo

Our laboratory and others have previously shown that cannabinoid receptor type-1 (CB1r) activity is neuroprotective and a modulator of brain ageing; a genetic disruption of CB1r signaling accelerates brain ageing, whereas the pharmacological stimulation of CB1r activity had the opposite effect. In this study, we have investigated if the lack of CB1r affects noradrenergic neurons in the locus coeruleus (LC), which are vulnerable to age-related changes; their numbers are reduced in patients with neurodegenerative diseases and probably also in healthy aged individuals. Thus, we compared LC neuronal numbers between cannabinoid 1 receptor knockout (Cnr1−/−) mice and their wild-type littermates. Our results reveal that old Cnr1−/− mice have less noradrenergic neurons compared to their age-matched wild-type controls. This result was also confirmed by the analysis of the density of noradrenergic terminals which proved that Cnr1−/− mice had less compared to the wild-type controls. Additionally, we assessed pro-inflammatory glial activity in the LC. Although the density of microglia in Cnr1−/− mice was enhanced, they did not show enhanced inflammatory profile. We hypothesize that CB1r activity is necessary for the protection of noradrenergic neurons, but its anti-inflammatory effect probably only plays a minor role in it.

2009 ◽  
Vol 10 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Aymen I. Idris ◽  
Antonia Sophocleous ◽  
Euphemie Landao-Bassonga ◽  
Meritxell Canals ◽  
Graeme Milligan ◽  
...  

2017 ◽  
Vol 112 (6) ◽  
pp. 933-939 ◽  
Author(s):  
Andrzej Wasilewski ◽  
Urszula Lewandowska ◽  
Paula Mosinska ◽  
Cezary Watala ◽  
Martin Storr ◽  
...  

2020 ◽  
Vol 34 (4) ◽  
pp. 429-440
Author(s):  
Lucas Gomes-de-Souza ◽  
Willian Costa-Ferreira ◽  
Leandro A Oliveira ◽  
Ricardo Benini ◽  
Carlos C Crestani

Background: Endocannabinoid neurotransmission in the bed nucleus of the stria terminalis is involved in the control of cardiovascular responses to stress. However, the local mechanisms involved is this regulation are not known. Aims: The purpose of this study was to assess an interaction of bed nucleus of the stria terminalis endocannabinoid neurotransmission with local nitrergic signaling, as well as to investigate the involvement of local N-methyl-D-aspartate glutamate receptor and nitric oxide signaling in the control of cardiovascular responses to acute restraint stress by bed nucleus of the stria terminalis endocannabinoid neurotransmission in rats. Methods: The first protocol evaluated the effect of intra-bed nucleus of the stria terminalis microinjection of the selective cannabinoid receptor type 1 receptor antagonist AM251 in nitrite/nitrate content in the bed nucleus of the stria terminalis following restraint stress. The other protocols evaluated the impact of local pretreatment with the selective N-methyl-D-aspartate glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase inhibitor Nω-propyl-L-arginine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the protein kinase G inhibitor KT5823 in restraint-evoked cardiovascular changes following bed nucleus of the stria terminalis treatment with AM251. Results: Bilateral microinjection of AM251 into the bed nucleus of the stria terminalis increased local nitric oxide release during restraint stress. Bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist also enhanced the tachycardia caused by restraint stress, but without affecting arterial pressure increase and sympathetic-mediated cutaneous vasoconstriction. The facilitation of restraint-evoked tachycardia following bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist was completely inhibited by local pretreatment with LY235959, Nω-propyl-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or KT5823. Conclusions: Our results provide evidence that bed nucleus of the stria terminalis endocannabinoid neurotransmission inhibits local N-methyl-D-aspartate/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling, and this mechanism is involved in the control of the cardiovascular responses to stress.


Author(s):  
Trenton C. Simmons ◽  
Sara M. Freeman ◽  
Nicholas S. Lackey ◽  
Brooke K. Dreyer ◽  
Devanand S. Manoli ◽  
...  

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