Sirtuins, brain and cognition: A review of resveratrol effects

Moraes, Daniel Silva; Moreira, Daniele Cristina; Andrade, João Marcus Oliveira; Santos, Sérgio Henrique Sousa

doi:10.1016/j.ibror.2020.06.004

Cited by 39 publications

(27 citation statements)

References 84 publications

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“…The former may be expected, given the lower measured levels of estradiol in the diestrus phase relative to proestrus rats 57 —who did not differ from males in estrogen receptor signaling proteins or phosphoproteins. Diestrus-specific enrichment in sirtuin signaling—involved in metabolism and cellular homeostasis 58 —is consistent with the ontological enrichment of energy metabolism-related proteins and phosphoproteins in diestrus compared to male rats. Moreover, the SIRT1 activator resveratrol has demonstrated effectiveness in alleviating ovariectomy-induced depressive-and anxiety-like behavior in mice via enhanced Sirt1 expression 59 , implicating sirtuin signaling in estradiol-modulated behavioral outcomes.…”

Section: Resultssupporting

confidence: 67%

Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine

Saland

Wilczak

Voss

et al. 2022

Sci Rep

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Numerous emotional and cognitive processes mediated by the hippocampus present differences between sexes and can be markedly influenced by hormonal status in males and females of several species. In rodents, the dorsal hippocampus (dHPC) is known to contribute to the rapid antidepressant actions of the NMDA receptor antagonist ketamine. We and others have demonstrated a greater sensitivity to the fast-acting antidepressant ketamine in female versus male rats that is estrogen- and progesterone-dependent. However, the underlying mechanisms remain unclear. Using an acute low dose (2.5 mg/kg) of ketamine that is behaviorally effective in female but not male rats, a label-free phosphoproteomics approach was employed to identify ketamine-induced changes in signaling pathway activation and phosphoprotein abundance within the dHPC of intact adult male rats and female rats in either diestrus or proestrus. At baseline, males and females showed striking dissimilarities in the dHPC proteome and phosphoproteome related to synaptic signaling and mitochondrial function—differences also strongly influenced by cycle stage in female rats. Notably, phosphoproteins enriched in PKA signaling emerged as being both significantly sex-dependent at baseline and also the primary target of ketamine-induced protein phosphorylation selectively in female rats, regardless of cycle stage. Reduced phosphoprotein abundance within this pathway was observed in males, suggesting bi-directional effects of low-dose ketamine between sexes. These findings present biological sex and hormonal milieu as critical modulators of ketamine’s rapid actions within this brain region and provide greater insight into potential translational and post-translational processes underlying sex- and hormone-dependent modulation of ketamine’s therapeutic effects.

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Section: Resultssupporting

confidence: 67%

Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine

Saland

Wilczak

Voss

et al. 2022

Sci Rep

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“…Thus, when SIRT1 was identified as a potential target for resveratrol, a compound enriched in red grapes [ 300 ], resveratrol became a popular strategy for the induction of endogenous PGC-1α activity and/or expression. While there are reports of resveratrol treatment increasing PGC-1α, NRF-1, and TFAM expression in the hippocampus [ 301 ] with some evidence for effects on cognition and mood in mouse models [ 302 , 303 ], trials in humans have been inconclusive [ 301 ], potentially due to its low bioavailability [ 304 ].…”

Section: Viable Avenues For Drug Discovery and Therapeutic Intervementioning

confidence: 99%

Dysregulation of PGC-1α-Dependent Transcriptional Programs in Neurological and Developmental Disorders: Therapeutic Challenges and Opportunities

McMeekin

Fox

Boas

et al. 2021

Cells

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Substantial evidence indicates that mitochondrial impairment contributes to neuronal dysfunction and vulnerability in disease states, leading investigators to propose that the enhancement of mitochondrial function should be considered a strategy for neuroprotection. However, multiple attempts to improve mitochondrial function have failed to impact disease progression, suggesting that the biology underlying the normal regulation of mitochondrial pathways in neurons, and its dysfunction in disease, is more complex than initially thought. Here, we present the proteins and associated pathways involved in the transcriptional regulation of nuclear-encoded genes for mitochondrial function, with a focus on the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α). We highlight PGC-1α’s roles in neuronal and non-neuronal cell types and discuss evidence for the dysregulation of PGC-1α-dependent pathways in Huntington’s Disease, Parkinson’s Disease, and developmental disorders, emphasizing the relationship between disease-specific cellular vulnerability and cell-type-specific patterns of PGC-1α expression. Finally, we discuss the challenges inherent to therapeutic targeting of PGC-1α-related transcriptional programs, considering the roles for neuron-enriched transcriptional coactivators in co-regulating mitochondrial and synaptic genes. This information will provide novel insights into the unique aspects of transcriptional regulation of mitochondrial function in neurons and the opportunities for therapeutic targeting of transcriptional pathways for neuroprotection.

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“…The complexity in interpreting the interplay between the liver (as the main controller of the systemic UCB level), the brain (neurological diseases) and the YPs is also present in the non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. NALFD is a pandemic condition involving also the pediatric population [ 174 , 175 ], and regarded as one of the newest risk factors for neurological diseases [ 176 , 177 ], with the life style and the diet regimen being key factors in the CNS pathology progression [ 178 , 179 , 180 ]. The liver and brain appear to be inter-connected at various levels (so-called liver brain axis): (1) A negative correlation between serum bilirubin concentrations and NAFLD stage has been reported [ 75 , 181 , 182 , 183 , 184 ]; (2) the modulation of HMOX1/CO/iron, in turn acting on sirtuin1 (Sirt1—see Table 2 ), a histone deacetylase controlling the adaptive mechanism to disease and the bilirubin transport in both organs [ 89 , 185 , 186 , 187 ] has been also demonstrated; and (3), the liver and brain may be connected by insulin resistance [ 183 ], a feature of the metabolic syndrome whose CNS consequences have been discussed in Section 2.4 .…”

Section: The Yellow Players (Yp)mentioning

confidence: 99%

The Role of Bilirubin and the Other “Yellow Players” in Neurodegenerative Diseases

et al. 2020

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Bilirubin is a yellow endogenous derivate of the heme catabolism. Since the 1980s, it has been recognized as one of the most potent antioxidants in nature, able to counteract 10,000× higher intracellular concentrations of H2O2. In the recent years, not only bilirubin, but also its precursor biliverdin, and the enzymes involved in their productions (namely heme oxygenase and biliverdin reductase; altogether the “yellow players”—YPs) have been recognized playing a protective role in diseases characterized by a chronic prooxidant status. Based on that, there is an ongoing effort in inducing their activity as a therapeutic option. Nevertheless, the understanding of their specific contributions to pathological conditions of the central nervous system (CNS) and their role in these diseases are limited. In this review, we will focus on the most recent evidence linking the role of the YPs specifically to neurodegenerative and neurological conditions. Both the protective, as well as potentially worsening effects of the YP’s activity will be discussed.

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Sirtuins, brain and cognition: A review of resveratrol effects

Cited by 39 publications

References 84 publications

Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine

Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine

Dysregulation of PGC-1α-Dependent Transcriptional Programs in Neurological and Developmental Disorders: Therapeutic Challenges and Opportunities

The Role of Bilirubin and the Other “Yellow Players” in Neurodegenerative Diseases

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