Premature Aging of the Hippocampal Neurogenic Niche in Adult Bmal1-deficient Mice

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2015 Jul 6

PMID 26142744

Citations 23

Authors

Amira A H Ali

Beryl Schwarz-Herzke

Anna Stahr

Timour Prozorovski

Orhan Aktas

Charlotte von Gall

Affiliations

Soon will be listed here.

Abstract

Hippocampal neurogenesis undergoes dramatic age-related changes. Mice with targeted deletion of the clock geneBmal1 (Bmal1(-/-)) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1(-/-) mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1(-/-) mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70 kDa and expression of the cell cycle inhibitor p21(Waf1/CIP1) were increased in adult Bmal1(-/-) mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age-dependent decline in adult neurogenesis presumably as a consequence of oxidative stress.

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References

Shetty G, Hattiangady B, Shetty A . Neural stem cell- and neurogenesis-related gene expression profiles in the young and aged dentate gyrus. Age (Dordr). 2013; 35(6):2165-76. PMC: 3824978. DOI: 10.1007/s11357-012-9507-6. View

Balu D, Lucki I . Adult hippocampal neurogenesis: regulation, functional implications, and contribution to disease pathology. Neurosci Biobehav Rev. 2008; 33(3):232-52. PMC: 2671071. DOI: 10.1016/j.neubiorev.2008.08.007. View

Fulco M, Schiltz R, Iezzi S, King M, Zhao P, Kashiwaya Y . Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. Mol Cell. 2003; 12(1):51-62. DOI: 10.1016/s1097-2765(03)00226-0. View

Redwine J, Kosofsky B, Jacobs R, Games D, Reilly J, Morrison J . Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: a magnetic resonance microscopy and stereologic analysis. Proc Natl Acad Sci U S A. 2003; 100(3):1381-6. PMC: 298781. DOI: 10.1073/pnas.242746599. View

Heine V, Maslam S, Joels M, Lucassen P . Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation. Neurobiol Aging. 2004; 25(3):361-75. DOI: 10.1016/S0197-4580(03)00090-3. View

Chiaverini N, De Ley M . Protective effect of metallothionein on oxidative stress-induced DNA damage. Free Radic Res. 2010; 44(6):605-13. DOI: 10.3109/10715761003692511. View

Ramsey K, Yoshino J, Brace C, Abrassart D, Kobayashi Y, Marcheva B . Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009; 324(5927):651-4. PMC: 2738420. DOI: 10.1126/science.1171641. View

Reppert S, Weaver D . Coordination of circadian timing in mammals. Nature. 2002; 418(6901):935-41. DOI: 10.1038/nature00965. View

Rakai B, Chrusch M, Spanswick S, Dyck R, Antle M . Survival of adult generated hippocampal neurons is altered in circadian arrhythmic mice. PLoS One. 2014; 9(6):e99527. PMC: 4062413. DOI: 10.1371/journal.pone.0099527. View

10.

Kempermann G, Jessberger S, Steiner B, Kronenberg G . Milestones of neuronal development in the adult hippocampus. Trends Neurosci. 2004; 27(8):447-52. DOI: 10.1016/j.tins.2004.05.013. View

11.

Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D . The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008; 134(2):329-40. PMC: 3526943. DOI: 10.1016/j.cell.2008.07.002. View

12.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

13.

Grechez-Cassiau A, Rayet B, Guillaumond F, Teboul M, Delaunay F . The circadian clock component BMAL1 is a critical regulator of p21WAF1/CIP1 expression and hepatocyte proliferation. J Biol Chem. 2007; 283(8):4535-42. DOI: 10.1074/jbc.M705576200. View

14.

Prozorovski T, Schulze-Topphoff U, Glumm R, Baumgart J, Schroter F, Ninnemann O . Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat Cell Biol. 2008; 10(4):385-94. DOI: 10.1038/ncb1700. View

15.

Bellet M, Orozco-Solis R, Sahar S, Eckel-Mahan K, Sassone-Corsi P . The time of metabolism: NAD+, SIRT1, and the circadian clock. Cold Spring Harb Symp Quant Biol. 2011; 76:31-8. DOI: 10.1101/sqb.2011.76.010520. View

16.

Chang H, Guarente L . SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell. 2013; 153(7):1448-60. PMC: 3748806. DOI: 10.1016/j.cell.2013.05.027. View

17.

Khapre R, Patel S, Kondratova A, Chaudhary A, Velingkaar N, Antoch M . Metabolic clock generates nutrient anticipation rhythms in mTOR signaling. Aging (Albany NY). 2014; 6(8):675-89. PMC: 4169861. DOI: 10.18632/aging.100686. View

18.

Okano H, Sawamoto K . Neural stem cells: involvement in adult neurogenesis and CNS repair. Philos Trans R Soc Lond B Biol Sci. 2008; 363(1500):2111-22. PMC: 2610183. DOI: 10.1098/rstb.2008.2264. View

19.

Brooks C, Gu W . How does SIRT1 affect metabolism, senescence and cancer?. Nat Rev Cancer. 2009; 9(2):123-8. PMC: 2857763. DOI: 10.1038/nrc2562. View

20.

Duncan M, Prochot J, Cook D, Smith J, Franklin K . Influence of aging on Bmal1 and Per2 expression in extra-SCN oscillators in hamster brain. Brain Res. 2012; 1491:44-53. PMC: 3530017. DOI: 10.1016/j.brainres.2012.11.008. View