The combination of HT-ac and HBET improves the cognitive and learning abilities of heat-stressed mice by maintaining mitochondrial function through the PKA–CREB–BDNF pathway

Li, Hongxia; Xu, Xin; Cai, Mengyu; Qu, Yicui; Ye, Chuyang; Ren, Zifu; shen, hui

doi:10.1039/d1fo04157f

Cited by 3 publications

(4 citation statements)

References 56 publications

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“…Interestingly, in TgCRND8 mouse models, it has been demonstrated that hydroxytyrosol diet supplementation results in substantial neuroprotection improving cognitive functions and leading to significant changes in the brain cortex and hippocampal areas with also a marked reduction of the TNF-α expression and astrocyte reaction [ 144 , 157 ]. Furthermore, hydroxytyrosol is able to ameliorate neuronal impairment via modulating mitochondrial oxidative stress, neuronal inflammation, and apoptosis [ 121 , 158 ]. In Caenorhabditis elegans models, it has been demonstrated that an olive-derived extract 20% rich in hydroxytyrosol is able to prevent the β-amyloid aggregation and oxidative stress associated to Alzheimer’s disease [ 124 , 159 ].…”

Section: Oxidative Stressmentioning

confidence: 99%

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Terracina

Petrella

Francati

et al. 2022

IJMS

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Both physiological and pathological aging processes induce brain alterations especially affecting the speed of processing, working memory, conceptual reasoning and executive functions. Many therapeutic approaches to reduce the impact of brain aging on cognitive functioning have been tested; unfortunately, there are no satisfactory results as a single therapy. As aging is partly contributed by free radical reactions, it has been proposed that exogenous antioxidants could have a positive impact on both aging and its associated manifestations. The aim of this report is to provide a summary and a subsequent review of the literature evidence on the role of antioxidants in preventing and improving cognition in the aging brain. Manipulation of endogenous cellular defense mechanisms through nutritional antioxidants or pharmacological compounds represents an innovative approach to therapeutic intervention in diseases causing brain tissue damage, such as neurodegeneration. Coherently with this notion, antioxidants, especially those derived from the Mediterranean diet such as hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain. The potential preventive activity of antioxidants should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability, able to bypass the blood-brain barrier limitation, and that are well standardized.

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Section: Oxidative Stressmentioning

confidence: 99%

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Terracina

Petrella

Francati

et al. 2022

IJMS

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“…According to the murine heat stress model with learning and memory impairment we established previously (Li et al, 2022), heat significantly induces declines in learning and memory abilities as assessed by the orientation navigation, the spatial probe, the shuttle box and the jumping stage tests. Additionally, it is widely believed that changes in synaptic connectivity play a crucial role in the processes underlying learning and memory.…”

Section: Discussionmentioning

confidence: 99%

“…The animal experiments conducted in this study were carried out following the protocols outlined in the guidelines for the Care and Use of Laboratory Animals, with full approval from the Institutional Animal Care and Use Committee of the Naval Medical University. The C57BL/6 mice were obtained, housed and treatment in accordance with the protocols outlined in our previous study (Li et al, 2022). Briefly, mice were divided into three groups (CON, HS and CDN1163, n=8).…”

Section: Animals and Cellsmentioning

confidence: 99%

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Heat stress induces calcium dyshomeostasis to subsequent cognitive impairment through ERS-mediated apoptosis via SERCA/PERK/eIF2α pathway

shen,

li,

pan

et al. 2023

Preprint

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Background: Heat exposure is an environmental stressor that has been associated with cognitive impairment. However, the neural mechanisms that underlie this phenomenon have yet to be extensively investigated. Methods: The Morris water maze test was utilized to assess cognitive performance. RNA sequencing was employed to discover the primary regulators and pathological pathways involved in cognitive impairment caused by heat. Prior to heat exposure in vivo and in vitro, activation of the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) was achieved by CDN1163. Hematoxylin-Eosin, Nissl staining, calcium imaging, transmission electron microscopy, western blot and immunofluorescence were utilized to visualize histological changes, intracellular calcium levels, endoplasmic reticulum stress (ERS) markers, apoptosis, and synaptic proteins alterations. Results: Heat stress (HS) significantly induced cognitive decline and neuronal damage in mice. By the transcriptome sequencing between control (n=5) and heat stress (n=5) mice in hippocampal tissues, we identified a reduction in the expression of the atp2a gene encoding SERCA, accompanied by a corresponding decrease in its protein level. Consequently, this dysregulation resulted in an excessive accumulation of intracellular calcium ions. Furthermore, HS exposure also activated ERS and apoptosis, as evidenced by the upregulation of p-PERK, p-eIF2α, and CHOP and caspase 3. Consistently, a reduction in postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) expressions indicated modifications in synaptic function. Notably, the impacts on neurons caused by HS were found to be mitigated by CDN1163 treatment both in vivo and in vitro. Additionally, SERCA-mediated ERS induced apoptosis was attenuated by GSK2606414 treatment via inhibiting PERK-eIF2α-CHOP axis that not only curtailed the level of caspase 3, but also elevated the levels of PSD95 and SYN. Conclusions: These findings highlight the significant impact of heat stress on cognitive impairment, and further elucidate the underlying mechanism involving SERCA/PERK/eIF2α pathway.

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Mitochondrial Complex I, a Possible Sensible Site of cAMP Pathway in Aging

Signorile

Rasmo

2023

Antioxidants

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In mammals during aging, reactive oxygen species (ROS), produced by the mitochondrial respiratory chain, cause oxidative damage of macromolecules leading to respiratory chain dysfunction, which in turn increases ROS mitochondrial production. Many efforts have been made to understand the role of oxidative stress in aging and age-related diseases. The complex I of the mitochondrial respiratory chain is the major source of ROS production and its dysfunctions have been associated with several forms of neurodegeneration, other common human diseases and aging. Complex I-ROS production and complex I content have been proposed as the major determinants for longevity. The cAMP signal has a role in the regulation of complex I activity and the decrease of ROS production. In the last years, an increasing number of studies have attempted to activate cAMP signaling to treat age-related diseases associated with mitochondrial dysfunctions and ROS production. This idea comes from a long-line of studies showing a main role of cAMP signal in the memory consolidation mechanism and in the regulation of mitochondrial functions. Here, we discuss several evidences on the possible connection between complex I and cAMP pathway in the aging process.

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The combination of HT-ac and HBET improves the cognitive and learning abilities of heat-stressed mice by maintaining mitochondrial function through the PKA–CREB–BDNF pathway

Abstract: The aim was to investigate whether the combination of Hydroxytyrosol acetate (HT-ac)and Ethyl β-hydroxybutyrate (HBET) can improve heat-stressed mice's cognition, meanwhile exploring the mechanism of action. Mice were divided into...

Cited by 3 publications

References 56 publications

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Heat stress induces calcium dyshomeostasis to subsequent cognitive impairment through ERS-mediated apoptosis via SERCA/PERK/eIF2α pathway

Mitochondrial Complex I, a Possible Sensible Site of cAMP Pathway in Aging

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