Rapamycin suppresses brain aging in senescence-accelerated OXYS rats

Kolosova, Nataliya G.; Vitovtov, Anton O.; Muraleva, Natalia A.; Akulov, A. E.; Stefanova, Natalia A.; Blagosklonny, Mikhail V.

doi:10.18632/aging.100573

Cited by 55 publications

(36 citation statements)

References 52 publications

(36 reference statements)

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“…Although neurodegenerative changes were also observed in OXYS rats even at the young age of 3 months [37,38], they were localized mainly in the cortical area while the size of hippocampus was even increased. The latter may evidence compensatory mechanisms that explain the absence of significant changes in olfactory function.…”

Section: Discussionmentioning

confidence: 87%

Comparative study of perception and processing of socially or sexually significant odor information in male rats with normal or accelerated senescence using fMRI

Tikhonova

Romaschenko

Akulov

et al. 2015

Behavioural Brain Research

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Section: Discussionmentioning

confidence: 87%

Comparative study of perception and processing of socially or sexually significant odor information in male rats with normal or accelerated senescence using fMRI

Tikhonova

Romaschenko

Akulov

et al. 2015

Behavioural Brain Research

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“…BCCAo also induced a reduction in spontaneous locomotion specifically in the Nfkb1-deficient female mice. Similarly, a strain of senescenceaccelerated OXYS rats has been reported to exhibit a dramatic decrease in open field rearing [50].…”

Section: Discussionmentioning

confidence: 96%

Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage

et al. 2016

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Transient forebrain ischemia induces delayed death of the hippocampal pyramidal neurons, particularly in the CA2 and medial CA1 area. Early pharmacological inhibition of inflammatory response can ameliorate neuronal death, but it also inhibits processes leading to tissue regeneration. Therefore, research efforts are now directed to modulation of post-ischemic inflammation, with the aim to promote beneficial effects of inflammation and limit adverse effects. Transcription factor NF-κB plays a key role in the inflammation and cell survival/apoptosis pathways. In the brain, NF-κB is predominantly found in the form of a heterodimer of p65 (RelA) and p50 subunit, where p65 has a transactivation domain while p50 is chiefly involved in DNA binding. In this study, we subjected middle-aged Nfkb1 knockout mice (lacking p50 subunit) and wild-type controls of both sexs to 17 min of transient forebrain ischemia and assessed mouse performance in a panel of behavioral tests after two weeks of post-operative recovery. We found that ischemia failed to induce clear memory and motor deficits, but affected spontaneous locomotion in genotype-and sex-specific way. We also show that both the lack of the NF-κB p50 subunit and female sex independently protected CA2 hippocampal neurons from ischemia-induced cell death. Additionally, the NF-κB p50 subunit deficiency significantly reduced ischemia-induced microgliosis, astrogliosis, and neurogenesis. Lower levels of hippocampal microgliosis significantly correlated with faster spatial learning. We conclude that NF-κB regulates the outcome of transient forebrain ischemia in middle-aged subjects in a sex-specific way, having an impact not only on neuronal death but also specific inflammatory responses and neurogenesis.

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“…Rapamycin causes a brain area-dependent reduction of sarkosyl insoluble tau levels, and a marked increase of autophagy markers [80]. Rapamycin, when given at a low dosage between 1.5 and 3.5 months of age, reduces total tau levels and p-Ser181 tau levels in OXYS rats, and increases total S6K1 and p-S6K1 levels [81].…”

Section: Mtorc1mentioning

confidence: 99%

Targeting Unselective Autophagy of Cellular Aggregates

Seneci

2015

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

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Rapamycin suppresses brain aging in senescence-accelerated OXYS rats

Cited by 55 publications

References 52 publications

Comparative study of perception and processing of socially or sexually significant odor information in male rats with normal or accelerated senescence using fMRI

Comparative study of perception and processing of socially or sexually significant odor information in male rats with normal or accelerated senescence using fMRI

Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage

Targeting Unselective Autophagy of Cellular Aggregates

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