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Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

Kolosova NG, Vitovtov AO, Muraleva NA, Akulov AE, Stefanova NA, Blagosklonny MV - Aging (Albany NY) (2013)

Bottom Line: Rapamycin decreased the percentage of animals with demyelination and the number of loci.Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity.We conclude that rapamycin in low chronic doses can suppress brain aging.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cytology and Genetics SB RAS, Acad. , 630090, Novosibirsk, Russia. gorislavna@mail.ru

ABSTRACT
Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

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MRI image of brain 4 month-old OXYS, Wistar rats and OXYS rats after rapamycin supplementation. (A) Hydrocephaly of lateral ventricle of OXYS rats (arrow). (B) Loci of demyelinization of the brain OXYS rats (arrow).
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Figure 6: MRI image of brain 4 month-old OXYS, Wistar rats and OXYS rats after rapamycin supplementation. (A) Hydrocephaly of lateral ventricle of OXYS rats (arrow). (B) Loci of demyelinization of the brain OXYS rats (arrow).


Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

Kolosova NG, Vitovtov AO, Muraleva NA, Akulov AE, Stefanova NA, Blagosklonny MV - Aging (Albany NY) (2013)

MRI image of brain 4 month-old OXYS, Wistar rats and OXYS rats after rapamycin supplementation. (A) Hydrocephaly of lateral ventricle of OXYS rats (arrow). (B) Loci of demyelinization of the brain OXYS rats (arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824413&req=5

Figure 6: MRI image of brain 4 month-old OXYS, Wistar rats and OXYS rats after rapamycin supplementation. (A) Hydrocephaly of lateral ventricle of OXYS rats (arrow). (B) Loci of demyelinization of the brain OXYS rats (arrow).
Bottom Line: Rapamycin decreased the percentage of animals with demyelination and the number of loci.Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity.We conclude that rapamycin in low chronic doses can suppress brain aging.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cytology and Genetics SB RAS, Acad. , 630090, Novosibirsk, Russia. gorislavna@mail.ru

ABSTRACT
Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

Show MeSH
Related in: MedlinePlus