| 1. |
- Caruso, Carla, et al.
(author)
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Activation of melanocortin 4 receptors reduces the inflammatory response and prevents apoptosis induced by lipopolysaccharide and interferon-gamma in astrocytes
- 2007
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:10, s. 4918-4926
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Journal article (peer-reviewed)abstract
- Alpha-MSH exerts an immunomodulatory action in the brain and may play a neuroprotective role acting through melanocortin 4 receptors (MC4Rs). In the present study, we show that MC4Rs are constitutively expressed in astrocytes as determined by immunocytochemistry, RT-PCR, and Western blot analysis. alpha-MSH (5 microm) reduced the nitric oxide production and the expression of inducible nitric oxide synthase (iNOS) induced by bacterial lipopolysaccharide (LPS, 1 microg/ml) plus interferon-gamma (IFN-gamma, 50 ng/ml) in cultured astrocytes after 24 h. alpha-MSH also attenuated the stimulatory effect of LPS/IFN-gamma on prostaglandin E(2) release and cyclooxygenase-2 (COX-2) expression. Treatment with HS024, a selective MC4R antagonist, blocked the antiinflammatory effects of alpha-MSH, suggesting a MC4R-mediated mechanism in the action of this melanocortin. In astrocytes, LPS/IFN-gamma treatment reduced cell viability, increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells and activated caspase-3. alpha-MSH prevented these apoptotic events, and this cytoprotective effect was abolished by HS024. LPS/IFN-gamma decreased Bcl-2, whereas it increased Bax protein expression in astrocytes, thus increasing the Bax/Bcl-2 ratio. Alpha-MSH produced a shift in Bax/Bcl-2 ratio toward astrocyte survival because it increased Bcl-2 expression and also prevented the effect of LPS/IFN-gamma on Bax and Bcl-2 expression. In summary, these findings suggest that alpha-MSH, through MC4R activation, attenuates LPS/IFN-gamma-induced inflammation by decreasing iNOS and COX-2 expression and prevents LPS/IFN-gamma-induced apoptosis of astrocytes by modulating the expression of proteins of the Bcl-2 family.
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| 2. |
- Gonzalez, Patricia Verónica, et al.
(author)
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Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors
- 2009
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In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 23:6, s. 817-822
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Journal article (peer-reviewed)abstract
- Interleukin-1beta (IL-1beta) significantly influences memory consolidation. Treatments that raise the level of IL-1beta in the brain, given after training, impair contextual fear conditioning. The melanocortin alpha-MSH exerts potent anti-inflammatory actions by physiologically antagonizing the effect of pro-inflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, with MC3R and MC4R predominating in the central nervous system. The present experiments show that injection of IL-1beta (5 ng/0.25 microl) in dorsal hippocampus up to 15 min after training decreased freezing during the contextual fear test. The treatment with IL-1beta (5 ng/0.25 microl) 12h after conditioning cause amnesia when animals were tested 7 days post training. Thus, our results also demonstrated that IL-1beta can influence persistence of long-term memory. We determined that animals previously injected with IL-1beta can acquire a new contextual fear memory, demonstrating that the hippocampus was not damaged. Treatment with alpha-MSH (0.05 microg/0.25 microl) blocked the effect of IL-1beta on contextual fear memory. Administration of the MC4 receptor antagonist HS014 (0.5 microg/0.25 microl) reversed the effect of alpha-MSH. However, treatment with gamma-MSH (0.5 microg/0.25 microl), an MC3 agonist, did not affect IL-1beta-induced impairment of memory consolidation. These results suggest that alpha-MSH, through central MC4R can inhibit the effect of IL-1beta on memory consolidation.
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| 3. |
- Herrera, Guadalupe, et al.
(author)
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Memory consolidation impairment induced by Interleukin-1 beta is associated with changes in hippocampal structural plasticity
- 2019
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In: Behavioural Brain Research. - : ELSEVIER SCIENCE BV. - 0166-4328 .- 1872-7549. ; 370
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Journal article (peer-reviewed)abstract
- Pro-inflammatory cytokines, particularly Interleukin-1 beta (IL-1 beta), can affect cognitive processes such as learning and memory. The aim of this study was to establish whether the effect of IL-1 beta on contextual fear memory is associated with changes in hippocampal structural plasticity. We also studied the effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent anti-inflammatory and neuro-protective peptide. Different groups of animals were implanted bilaterally in dorsal hippocampus (DH). After recovery they were conditioned for contextual fear memory and received the different treatments (vehicle, IL-1 beta, alpha-MSH or IL-1 beta + alpha-MSH). Memory was assessed 24 hs after conditioning and immediately after rats were perfused for dendritic spine analysis. Our results show that local hippocampal administration of IL-1 beta just after memory encoding induced impairment in contextual memory and a reduction in the total density of CA1 hippocampal dendritic spines, particularly the mature ones. alpha-MSH administration reversed the IL-1 beta induced changes. The results suggest that neuro-inflammation induced by IL-1 beta interferes with experience-dependent structural plasticity in DH whereas alpha-MSH has a beneficial modulatory role in preventing this effect.
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| 4. |
- Machado, Ivana, et al.
(author)
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IL-1 beta reduces GluAl phosphorylation and its surface expression during memory reconsolidation and cc-melanocyte-stimulating hormone can modulate these effects
- 2018
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In: Neuropharmacology. - : Elsevier. - 0028-3908 .- 1873-7064. ; 128, s. 314-323
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Journal article (peer-reviewed)abstract
- Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-beta (IL-beta) influences hippocampus-dependent memories. We previously reported that administration of IL-1 beta in dorsal hippocampus impaired contextual fear memory reconsolidation. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (a-MSH). Our results also demonstrated that IL-1 beta produced a significant decrease in glutamate release from dorsal hippo campus synaptosomes after reactivation of the fear memory. Therefore, we investigated whether IL-beta administration can affect GIuA1 AMPA subunit phosphorylation, surface expression, and total expression during reconsolidation of a contextual fear memory. Also, we studied the modulatory effect of alpha-MSH. We found that IL-beta reduced phosphorylation of this subunit at Serine 831 and Serine 845 60 min after contextual fear memory reactivation. The intrahippocampal administration of IL-beta after memory reactivation also induced a decrease in surface expression and total expression of GIuA1. alpha-MSH prevented the effect of IL-beta on GIuAI phosphorylation in Serine 845, but not in Serine 831. Moreover, treatment with alpha-MSH also prevented the effect of the cytokine on GluAl surface and total expression after memory reactivation. Our results demonstrated that IL-beta regulates phosphorylation of GIuAI and may thus play an important role in modulation of AMPAR function and synaptic plasticity in the brain. These findings further illustrate the importance of IL-beta in cognition processes dependent on the hippocampus, and also reinforced the fact that alpha-MSH can reverse IL-1 beta effects on memory reconsolidation. (C) 2017 Elsevier Ltd. All rights reserved.
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| 5. |
- Machado, Ivana, et al.
(author)
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Interleukin-1 beta-induced memory reconsolidation impairment is mediated by a reduction in glutamate release and zif268 expression and alpha-melanocyte-stimulating hormone prevented these effects
- 2015
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In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 46, s. 137-146
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Journal article (peer-reviewed)abstract
- The immune system is an important modulator of learning, memory and neural plasticity. Interleukin 1 13 (IL-1 beta), a pro-inflammatory cytokine, significantly affects several cognitive processes. Previous studies by our group have demonstrated that intrahippocampal administration of IL-1 beta impairs reconsolidation of contextual fear memory. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (alpha-MSH). The mechanisms underlying the effect of IL-1 beta on memory reconsolidation have not yet been established. Therefore, we examined the effect of IL-1 beta on glutamate release, ERK phosphorylation and the activation of the transcription factor zinc finger- 268 (zif268) during reconsolidation. Our results demonstrated that IL-1 beta induced a significant decrease of glutamate release after reactivation of the fear memory and this effect was related to calcium concentration in hippocampal synaptosomes. IL-1 beta also reduced ERK phosphorylation and zif268 expression in the hippocampus. Central administration of a-MSH prevented the decrease in glutamate release, ERK phosphorylation and zif268 expression induced by IL-1 beta. Our results establish possible mechanisms involved in the detrimental effect of IL-1 beta on memory reconsolidation and also indicate that a-MSH may exert a beneficial modulatory role in preventing IL-1 beta effects.
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| 6. |
- Machado, Ivana, et al.
(author)
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α-Melanocyte-stimulating hormone (α-MSH) reverses impairment of memory reconsolidation induced by interleukin-1 beta (IL-1 beta) hippocampal infusions
- 2010
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In: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 31:11, s. 2141-2144
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Journal article (peer-reviewed)abstract
- Interleukin-1 beta (IL-1β) significantly influences cognitive processes. Treatments which raise the level of IL-1β in the brain impair memory consolidation in contextual fear conditioning. However, the effect of IL-1β on memory reconsolidation has not yet been established. The melanocortin α-melanocyte-stimulating hormone (α-MSH) exerts potent anti-inflammatory actions by antagonizing the effect of proinflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, of which MC3R and MC4R are predominant in the central nervous system. The present experiments show that the injection of IL-1β (5 ng/0.25 μl) in dorsal hippocampus up to 30 min after re-exposition to the context decreases freezing during the contextual fear test. Impairment of memory reconsolidation was reversed by treatment with α-MSH (0.05 μg/0.25 μl). Administration of the MC4 receptor antagonist HS014 (0.5 μg/0.25 μl) blocked the effect of α-MSH. These results suggest that IL-1β may influence memory reconsolidation and that activation of central MC4R could lead to improve cognitive performance.
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