Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment Induced by Delta9-Tetrahydrocannabinol.
Neuropsychopharmacol.. 2017-08-17; 43(5): 1021-1031
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1. Neuropsychopharmacology. 2018 Apr;43(5):1021-1031. doi: 10.1038/npp.2017.175.
Epub 2017 Aug 17.
Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment
Induced by Delta9-Tetrahydrocannabinol.
Busquets-Garcia A(1), Gomis-González M(1), Salgado-Mendialdúa V(1), Galera-López
L(1), Puighermanal E(1), Martín-García E(1), Maldonado R(1), Ozaita A(1).
(1)Laboratory of Neuropharmacology, Department of Experimental and Health
Sciences, University Pompeu Fabra, Barcelona, Spain.
Cannabis affects cognitive performance through the activation of the
endocannabinoid system, and the molecular mechanisms involved in this process are
poorly understood. Using the novel object-recognition memory test in mice, we
found that the main psychoactive component of cannabis,
delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory
specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the
systemic or intra-hippocampal pre-treatment with the PKC inhibitors prevented the
short-term, but not the long-term, memory impairment induced by THC. In contrast,
systemic pre-treatment with mammalian target of rapamycin complex 1 inhibitors,
known to block the amnesic-like effects of THC on long-term memory, did not
modify such a short-term cognitive deficit. Immunoblot analysis revealed a
transient increase in PKC signaling activity in the hippocampus after THC
treatment. Thus, THC administration induced the phosphorylation of a specific Ser
residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms.
This significant immunoreactive band that paralleled cognitive performance did
not match in size with the major PKC isoforms expressed in the hippocampus except
for PKCθ. Moreover, THC transiently enhanced the phosphorylation of the
postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner.
These data demonstrate that THC alters short-term object-recognition memory
through hippocampal PKC/neurogranin signaling.
PMID: 28816239 [Indexed for MEDLINE]