Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence indicates that the polysialylated neural cell adhesion molecule (PSA-NCAM) is involved in hippocampal plasticity. On the other hand, CB1 receptor activation is known to disturb some hippocampal processes involving plastic changes, such as learning and memory. Therefore, the present study investigated the effect of HU-210, a CB1 receptor agonist, on the expression of PSA-NCAM protein in the dentate gyrus (DG) and CA3 region of the rat hippocampus. It was found that at a dose of 0.1 mg/kg i.p. of HU-210, the number of PSA-NCAM immunoreactive (IR) cells in the DG declined in a time-dependent manner. The decrease in PSA-NCAM expression was observed at 1 and 2 days (ca. 21% and 30%, respectively), but not after 4 h and 4 days following HU-210 administration. However, HU-210 treatment did not change the length density of PSA-NCAM immunopositive processes in CA3 mossy fibers at all the time points measured. The effect observed in the DG on day 2 was blocked by AM-251 (1 mg/kg, i.p.), a CB1 receptor antagonist, given 30 min before HU-210. Neither the number of Ki-67 (IR) cells (a marker of proliferation) nor the number of doublecortin-IR cells (a marker of immature neurons) was affected by HU-210 (0.1 mg/kg, i.p.) treatment at any of the time points. An analysis of co-localization of CB1 receptor protein with PSA-NCAM protein revealed that both proteins were not present in the same population of neurons in the subgranular layer of the DG. The observed changes in PSA-NCAM expression were not related to the reduction of proliferation or differentiation of newly born cells, but were possible due to alternations in the synaptic activity in the DG. However, such alteration in the PSA-NCAM expression may change the timing of the functional maturation of newly born neurons. Moreover, the above finding suggests that acute activation of CB1 receptors may result in the stiffening of the hippocampal structure and susceptibility to plastic changes and may lead to functional impairment governed by alterations in the hippocampal structure.
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PMID:Acute activation of CB1 cannabinoid receptors transiently decreases PSA-NCAM expression in the dentate gyrus of the rat hippocampus. 1735 76

We investigated the role of CB1 receptors in hippocampal-dependent memory consolidation mediated by polysialylated neural cell adhesion molecule (PSA-NCAM) during contextual fear conditioning (CFC). The CB1 receptor agonist 3-(1,1-dimethylheptyl)-(-)-11-hydroxy-Delta(8)-tetrahydrocannabinol (HU-210) (0.1 mg/kg) was given immediately after training during the memory consolidation phase, and freezing behavior was measured 24 h after conditioning. Administration of HU-210 attenuated freezing behavior measured in CFC. Western blot analysis showed that CFC induced a decrease in the expression of NCAM-180, but did not change the level of NCAM-140 and increased PSA-NCAM expression measured 24 h after training in the rat hippocampus. HU-210 (0.1 mg/kg) injection did not affect the reduction in NCAM-180 levels induced by CFC, but it blocked the increase in PSA-NCAM expression. Since the dentate gyrus (DG) of the hippocampus is known to be involved in memory consolidation and expresses a high level of PSA-NCAM protein, we measured the effects of CFC and HU-210 administration on PSA-NCAM-immunoreactive (IR) cells in the DG. CFC caused an increase in the number of PSA-NCAM-IR cells in the DG, but not K(i)-67- or doublecortin (DCX)-IR cells. This increase in PSA-NCAM-IR cells was abolished by HU-210 injection. Administration of the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM-251) (3 mg/kg immediately before HU-210) inhibited the effects of HU-210 on freezing behavior and PSA-NCAM expression in the DG. These results indicate that activation of CB1 receptors disturbs consolidation of fear memory in CFC, likely by affecting PSA-NCAM expression in the DG, which plays an important role in synaptic rearrangement during the formation of memory traces.
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PMID:Activation of CB1 cannabinoid receptors impairs memory consolidation and hippocampal polysialylated neural cell adhesion molecule expression in contextual fear conditioning. 1911 37

The present study investigated the potential role of the extracellular signal-regulated kinase (ERK) pathway in the alternation of polysialylated neural cell adhesion molecule (PSA-NCAM) expression and proliferation rates in the dentate gyrus (DG) evoked by activation of the CB1 receptor. When given at a dose of 0.1 mg/kg, the CB1 receptor agonist, 3-(1,1-dimethylheptyl)-11-hydroxy-Delta(8)-tetrahydrocannabinol (HU-210), increased the levels of the phosphorylated forms of ERK (pERK1 and pERK2) in the hippocampus when measured 30 min after injection. This HU-210-induced effect was inhibited by alpha-{amino[(4-aminophenyl)thio]methylene}-2-(trifluoromethyl) benzeneacetonitrile (SL327, 30 mg/kg) - an inhibitor of mitogen-activated protein kinase kinase (MEK1/2), the upstream kinase of ERK - given 1 h before HU-210 administration. Additionally, SL327 alone significantly attenuated the basal level of both pERK1 and pERK2. HU-210 (0.1 mg/kg) decreased the number of PSA-NCAM-immunoreactive (IR) cells but did not affect the rate of proliferation, which was analyzed as the number of Ki-67-IR cells measured in the DG 2 days after HU-210 administration. The data indicated that SL327 (30 mg/kg) alone decreased the number of PSA-NCAM-IR cells 2 days after treatment. Joint administration of SL327 and HU-210 decreased the number of PSA-NCAM cells more robustly than did the administration of either alone. In addition, SL327 did not decrease the number of Ki-67-IR cells, while pretreatment with SL327 1 h before HU-210 administration did. These results suggest that stimulation of the ERK cascade caused by CB1 receptor activation is not involved in hippocampal plasticity governed by PSA-NCAM expression.
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PMID:ERK signalling pathway is not involved in PSA-NCAM-dependent alterations of hippocampal plasticity evoked by CB1 receptor activation. 2008 Dec 35