Synaptic plasticity alterations associated with memory impairment induced by deletion of CB2 cannabinoid receptors.

María S. García-Gutiérrez, Antonio Ortega-Álvaro, Arnau Busquets-García, Jose M. Pérez-Ortiz, Laura Caltana, María Jimena Ricatti, Alicia Brusco, Rafael Maldonado, Jorge Manzanares
Neuropharmacology. 2013-10-01; 73: 388-396
DOI: 10.1016/j.neuropharm.2013.05.034

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1. Neuropharmacology. 2013 Oct;73:388-96. doi: 10.1016/j.neuropharm.2013.05.034.
Epub 2013 Jun 21.

Synaptic plasticity alterations associated with memory impairment induced by
deletion of CB2 cannabinoid receptors.

García-Gutiérrez MS(1), Ortega-Álvaro A, Busquets-García A, Pérez-Ortiz JM,
Caltana L, Ricatti MJ, Brusco A, Maldonado R, Manzanares J.

Author information:
(1)Instituto de Neurociencias, Campus de San Juan, Universidad Miguel
Hernández-CSIC, San Juan de Alicante, Alicante, Spain.

In this study, the role of CB₂r on aversive memory consolidation was further
evaluated. Mice lacking CB₂r (CB2KO) and their corresponding littermates (WT)
were exposed to the step-down inhibitory avoidance test (SDIA). MAP2, NF200 and
synaptophysin (SYN)-immunoreactive fibers were studied in the hippocampus (HIP)
of both genotypes. The number of synapses, postsynaptic density thickness and the
relation between the synaptic length across the synaptic cleft and the distance
between the synaptic ends were evaluated in the HIP (dentate gyrus (DG) and CA1
fields) by electron microscopy. Brain-derived neurotrophic factor (BDNF),
glucocorticoid receptor (NR3C1) gene expressions and mTOR/p70S6K signaling
cascade were evaluated in the HIP and prefrontal cortex (PFC). Finally, the
effects of acute administration of CB₂r-agonist JWH133 or CB2r-antagonist AM630
on memory consolidation were evaluated in WT mice by using the SDIA. The lack of
CB₂r impaired aversive memory consolidation, reduced MAP2, NF200 and
SYN-immunoreactive fibers and also reduced the number of synapses in DG of CB2KO
mice. BDNF and NR3C1 gene expression were reduced in the HIP of CB2KO mice. An
increase of p-p70S6K (T389 and S424) and p-AKT protein expression was observed in
the HIP and PFC of CB2KO mice. Interestingly, administration of AM630 impaired
aversive memory consolidation, whereas JWH133 enhanced it. Further functional and
molecular assessments would have been helpful to further support our conclusions.
These results revealed that CB₂r are involved in memory consolidation, suggesting
that this receptor could be a promising target for developing novel treatments
for different cognitive impairment-related disorders.

Copyright © 2013 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neuropharm.2013.05.034
PMID: 23796670 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus