Molecular mechanisms mediating gastrin-releasing peptide receptor modulation of memory consolidation in the hippocampus

Roesler, Rafaël; Luft, Tatiana; Oliveira, Sérgio Eduardo Silva de; Farias, Caroline Brunetto de; Almeida, Vânia; Quevedo, Joao L De; Dal‐Pizzol, Felipe; Schröder, Nadja; Izquierdo, Iván; Schwartsmann, Gilberto

doi:10.1016/j.neuropharm.2006.03.033

Cited by 71 publications

(73 citation statements)

References 55 publications

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“…Our present report is in contrast to those findings and suggests that at least under some conditions (namely, coactivation with GRPR), stimulation of the cAMP/PKA cascade might promote rather than inhibit proliferation of glioblastoma cells. Our finding is consistent with data indicating that inhibition of tumor growth by GRPR antagonism is related to reduced cAMP production in SW-1990 human pancreatic adenocarcinoma [18], as well as to our previous in vivo study showing that neuronal GRPR interacts with the cAMP/PKA pathway in regulating brain function in rats [25]. Future experiments should examine whether PKA inhibitors can inhibit proliferation and/or prevent stimulatory effects of GRP agonists in glioma cells.…”

Section: Discussionsupporting

confidence: 92%

Stimulation of Proliferation of U138-MG Glioblastoma Cells by Gastrin-Releasing Peptide in Combination with Agents That Enhance cAMP Signaling

Farias

Lima²,

Lima³

et al. 2008

Oncology

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Increasing evidence indicates that gastrin-releasing peptide (GRP) acts as an autocrine growth factor for brain tumors. However, it remains unclear whether the cAMP/protein kinase A (PKA) signaling pathway plays a role in mediating the mitogenic effects of GRP. We show here that GRP combined with agents that stimulate the cAMP/PKA pathway promotes proliferation of human gliobastoma cells. Treatment with GRP combined with the adenylyl cyclase activator forskolin, the cAMP analog 8-Br-cAMP or the phosphodiesterase type IV inhibitor rolipram increased proliferation of U138-MG cells in vitro measured by MTT assay. None of the compounds had an effect when given alone. GRP receptor (GRPR) mRNA and protein expression in U138-MG cells was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The results suggest that GRP and the GRPR interact with the cAMP/PKA signaling pathway in stimulating cancer cell proliferation.

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Section: Discussionsupporting

confidence: 92%

Stimulation of Proliferation of U138-MG Glioblastoma Cells by Gastrin-Releasing Peptide in Combination with Agents That Enhance cAMP Signaling

Farias

Lima²,

Lima³

et al. 2008

Oncology

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“…Notably, in experiments examining cancer cell growth (27,30,31), as well as in other experimental models (32)(33)(34), GRPR agonists and antagonists often show drug-response patterns, in which intermediate doses have more pronounced biological, whereas higher doses have no or even contrary effects. Moreover, the lack of a significant effect of RC-3095 in the present study might be owed to its lower potency compared to RC-3940-II.…”

Section: Discussionmentioning

confidence: 99%

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Cornélio

Farias

Prusch

et al. 2012

Molecular and Clinical Oncology

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Abstract. Neuropeptide and neurotrophin receptors are increasingly important molecular targets in cancer. Scientific findings indicate that compounds blocking gastrin-releasing peptide receptors (GRPR) or tropomyosin receptor kinase (Trk) receptors are likely to have antiproliferative activities against cancer cells. The present study aimed to demonstrate that, in contrast to previous findings, GRPR activation reduces, whereas its blockade increases the viability of breast, ovarian and cervical cancer cell lines. However, consistent with previous studies, Trk inhibition was demonstrated to reduce the viability of these cells. MCF-7 (breast), OVCAR-3 (ovarian) and HeLa (cervical) human cancer cell lines were treated with GRP, the GRPR antagonists RC-3095 and RC-3940-II, brain-derived neurotrophic factor (BDNF) and the Trk antagonist K252α. Cell viability was measured by the MTT assay. Expression of GRPR and BDNF was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). GRP reduced, whereas RC-3940-II enhanced the viability of the three cell lines. Treatment with K252α inhibited the viability of the cell lines, while BDNF increased the viability of OVCAR-3 cells. The results supported the hypothesis that GRPR and BDNF/TrkB signaling regulates cancer cell viability. Most importantly, these findings are the first to demonstrate that GRPR blockade can stimulate, rather than inhibits the viability of breast and gynecologic cancer cell lines.

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“…5D; Supplemental Table 1). Grp modulates synaptic plasticity and memory formation (Shumyatsky et al 2002;Roesler et al 2006Roesler et al , 2009, and Crym is highly expressed in hippocampal and cortical neurons, where it is thought to play a role in neuronal specification (Arlotta et al 2005;Lein et al 2007;Suzuki et al 2007). We independently confirmed that Grp and Crym were significantly down-regulated in FoxO6 mutant mice compared with wild-type mice using RT-qPCR (Supplemental Fig.…”

Section: Foxo6 Is Necessary For Neuronal Synchronization Upon Novel Omentioning

confidence: 99%

FoxO6 regulates memory consolidation and synaptic function

et al. 2012

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The FoxO family of transcription factors is known to slow aging downstream from the insulin/IGF (insulin-like growth factor) signaling pathway. The most recently discovered FoxO isoform in mammals, FoxO6, is highly enriched in the adult hippocampus. However, the importance of FoxO factors in cognition is largely unknown. Here we generated mice lacking FoxO6 and found that these mice display normal learning but impaired memory consolidation in contextual fear conditioning and novel object recognition. Using stereotactic injection of viruses into the hippocampus of adult wild-type mice, we found that FoxO6 activity in the adult hippocampus is required for memory consolidation. Genome-wide approaches revealed that FoxO6 regulates a program of genes involved in synaptic function upon learning in the hippocampus. Consistently, FoxO6 deficiency results in decreased dendritic spine density in hippocampal neurons in vitro and in vivo. Thus, FoxO6 may promote memory consolidation by regulating a program coordinating neuronal connectivity in the hippocampus, which could have important implications for physiological and pathological age-dependent decline in memory.

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Molecular mechanisms mediating gastrin-releasing peptide receptor modulation of memory consolidation in the hippocampus

Cited by 71 publications

References 55 publications

Stimulation of Proliferation of U138-MG Glioblastoma Cells by Gastrin-Releasing Peptide in Combination with Agents That Enhance cAMP Signaling

Stimulation of Proliferation of U138-MG Glioblastoma Cells by Gastrin-Releasing Peptide in Combination with Agents That Enhance cAMP Signaling

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

FoxO6 regulates memory consolidation and synaptic function

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