Differential expression of the neuronal CB1 cannabinoid receptor in the hippocampus of male Ts65Dn Down syndrome mouse model

https://doi.org/10.1016/j.mcn.2022.103705Get rights and content
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Highlights

  • Segregation of CB1 distribution between the dorsal and ventral HPC of Ts65Dn mice

  • Alteration of CB1 mRNA and protein levels in the dHPC of Ts65Dn mice

  • Increase of CB1 mRNA in GABAergic interneurons of dHPC of Ts65Dn mice

  • Decrease of CB1 mRNA in pyramidal layers of dHPC of Ts65Dn mice

  • CB1 as a potential therapeutic target for HPC-related disorders in DS

Abstract

Down syndrome (DS) or Trisomy 21 is the most common genetic cause of mental retardation with severe learning and memory deficits. DS is due to the complete or partial triplication of human chromosome 21 (HSA21) triggering gene overexpression and protein synthesis alterations responsible for a plethora of mental and physical phenotypes. Among the diverse brain target systems that affect hippocampal-dependent learning and memory deficit impairments in DS, the upregulation of the endocannabinoid system (ECS), and notably the overexpression of the cannabinoid type-1 receptor (CB1), seems to play a major role. Combining various protein and gene expression targeted approaches using western blot, qRT-PCR and FISH techniques, we investigated the expression pattern of ECS components in the hippocampus (HPC) of male Ts65Dn mice. Among all the molecules that constitute the ECS, we found that the expression of the CB1 is altered in the HPC of Ts65Dn mice. CB1 distribution is differentially segregated between the dorsal and ventral part of the HPC and within the different cell populations that compose the HPC. CB1 expression is upregulated in GABAergic neurons of Ts65Dn mice whereas it is downregulated in glutamatergic neurons. These results highlight a complex regulation of the CB1 encoding gene (Cnr1) in Ts65Dn mice that could open new therapeutic solutions for this syndrome.

Abbreviations

AA
arachidonic acid
ABHD12
α,β-hydrolase-12
AEA
anandamide
AD
Alzheimer-like disease
CA1, 2 or 3
Cornus Ammonis 1, 2 or 3
CB1
cannabinoid type-1 receptor
CB2
cannabinoid type-2 receptor
CD
cognitive deficit
Cnr1
CB1 encoding gene
Cnr2
CB2 encoding gene
D-FISH
double fluorescent in situ hybridization
DAGL
diacylglycerol lipase
DG
Dentate Gyrus
dHPC
dorsal hippocampus
DS
Down syndrome
eCBs
endocannabinoids
ECS
endocannabinoid system
ETA
ethanolamine
FAAH
fatty acid amide hydrolase
GAD
glutamic acid decarboxylase 65 kDa and 67 kDa
HSA21
human chromosome 21
LMol
lacunosum moleculare strata
MAGL
monoacylglycerol lipase
NAPE
N-acyl phosphatidylethanolamine
NAPE-PLD
N-acyl phosphatidylethanolamine phospholipase D
PFC
prefrontal cortex
PIP2
phosphatidylinositol 4,5-bisphosphate
PLC
phospholipase C
Po
polymorph dentate gyrus
Py
pyramidal layers
SLu
stratum lucidum
vHPC
ventral hippocampus
2-AG
2-arachidonoylglycerol

Keywords

Endocannabinoid system (ECS)
Cannabinoid type-1 receptor (CB1)
Down syndrome (DS)
Ts65Dn mouse
Hippocampus (HPC)

Cited by (0)

1

These authors contributed equally to this work.

2

Current address: Aelis Farma, 33077 Bordeaux, France.