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Failure of senolytic treatment to prevent cognitive decline in a female rodent model of aging

Rani, Asha, Bean, Linda, Budamagunta, Vivekananda, Kumar, Ashok, Foster, Thomas C.·2024·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2024.1384554PMC PMC11133672
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Abstract

There are sex differences in vulnerability and resilience to the stressors of aging and subsequent age-related cognitive decline. Cellular senescence occurs as a response to damaging or stress-inducing stimuli. The response includes a state of irreversible growth arrest, the development of a senescence-associated secretory phenotype, and the release of pro-inflammatory cytokines associated with aging and age-related diseases. Senolytics are compounds designed to eliminate senescent cells. Our recent work indicates that senolytic treatment preserves cognitive function in aging male F344 rats. The current study examined the effect of senolytic treatment on cognitive function in aging female rats. Female F344 rats (12 months) were treated with dasatinib (1.2 mg/kg) + quercetin (12 mg/kg) or ABT-263 (12 mg/kg) or vehicle for 7 months. Examination of the estrus cycle indicated that females had undergone estropause during treatment. Senolytic treatment may have increased sex differences in behavioral stress responsivity, particularly for the initial training on the cued version of the watermaze. However, pre-training on the cue task reduced stress responsivity for subsequent spatial training and all groups learned the spatial discrimination. In contrast to preserved memory observed in senolytic-treated males, all older females exhibited impaired episodic memory relative to young (6-month) females. We suggest that the senolytic treatment may not have been able to compensate for the loss of estradiol, which can act on aging mechanisms for anxiety and memory independent of cellular senescence.

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FIGURE 1 No effect of treatment on weight and grip strength. (A) Schematic of the time course of treatment and testing. Rats were treated via oral gavage for 5 consecutive days with a 2 week break in between treatment cycles. Animals were behaviorally tested during week 25 followed by a final treatment on week 27. Final weight and grip strength were measured on week 30, 2 weeks after the final treatment. (B) Mean weight (±SEM) for older animals over the course of treatment and weight of the Young (YNG) group (blue circle) measured at the same time as the final weight for aged animals. (C) Grip strength normalized to weight. The asterisk indicates significantly greater grip strength of YNG relative to the three older groups.
FIGURE 1 No effect of treatment on weight and grip strength. (A) Schematic of the time course of treatment and testing. Rats were treated via oral gavage for 5 consecutive days with a 2 week break in between treatment cycles. Animals were behaviorally tested during week 25 followed by a final treatment on week 27. Final weight and grip strength were measured on week 30, 2 weeks after the final treatment. (B) Mean weight (±SEM) for older animals over the course of treatment and weight of the Young (YNG) group (blue circle) measured at the same time as the final weight for aged animals. (C) Grip strength normalized to weight. The asterisk indicates significantly greater grip strength of YNG relative to the three older groups.CC BY · PubMed Central
FIGURE 2 Effect of senolytic treatments on cue discrimination behavior. Mean (±SEM) latency (A), swim speed (C), and escape distance (E) for each training block for the cue discrimination task. The mean (+SEM) latency (B), swim speed (D), and escape distance (F) averaged across blocks illustrates that the ADQ group exhibited an increase in latency and distance to escape and the AA group exhibited an increase in swim speed on the cue task. Asterisks indicate a significant difference relative to the ADQ group. Pound signs indicate a significant difference relative to the AA group.
FIGURE 2 Effect of senolytic treatments on cue discrimination behavior. Mean (±SEM) latency (A), swim speed (C), and escape distance (E) for each training block for the cue discrimination task. The mean (+SEM) latency (B), swim speed (D), and escape distance (F) averaged across blocks illustrates that the ADQ group exhibited an increase in latency and distance to escape and the AA group exhibited an increase in swim speed on the cue task. Asterisks indicate a significant difference relative to the ADQ group. Pound signs indicate a significant difference relative to the AA group.CC BY · PubMed Central
FIGURE 3 Effect of senolytic treatments on spatial discrimination behavior. Mean (±SEM) latency (A), swim speed (C), and escape distance (E) for each training block for the spatial discrimination task. The mean (+SEM) latency (B), swim speed (D), and escape distance (F) averaged across blocks illustrate that the YNG animals exhibited a slower swim speed and shorter distance, with no differences between all the older groups. Asterisks indicate a significant difference relative to the YNG group.
FIGURE 3 Effect of senolytic treatments on spatial discrimination behavior. Mean (±SEM) latency (A), swim speed (C), and escape distance (E) for each training block for the spatial discrimination task. The mean (+SEM) latency (B), swim speed (D), and escape distance (F) averaged across blocks illustrate that the YNG animals exhibited a slower swim speed and shorter distance, with no differences between all the older groups. Asterisks indicate a significant difference relative to the YNG group.CC BY · PubMed Central
FIGURE 4 No effect of senolytic treatments on spatial memory. The figure provides the percent time spent in the goal and opposite quadrants (mean + SEM) for the (A) acquisition and (B) retention probe trials on the watermaze. Asterisks indicate a difference relative to chance (25%).
FIGURE 4 No effect of senolytic treatments on spatial memory. The figure provides the percent time spent in the goal and opposite quadrants (mean + SEM) for the (A) acquisition and (B) retention probe trials on the watermaze. Asterisks indicate a difference relative to chance (25%).CC BY · PubMed Central
FIGURE 5 No effect of age or senolytic treatments on memory for inhibitory avoidance. Box plots for latency to enter the dark compartment of inhibitory avoidance during (A) day 1 training and (B) day 2 retention testing. Pound signs indicate a difference in latency on day 1 relative to AV and ADQ.
FIGURE 5 No effect of age or senolytic treatments on memory for inhibitory avoidance. Box plots for latency to enter the dark compartment of inhibitory avoidance during (A) day 1 training and (B) day 2 retention testing. Pound signs indicate a difference in latency on day 1 relative to AV and ADQ.CC BY · PubMed Central

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Research works printed but not linked: 73

  1. Barter, 2021, Adulthood systemic inflammation accelerates the trajectory of age-related cognitive decline., Aging, 13, 22092, 10.18632/aging.203588 · DOI
  2. Barter, 2020, Differential effect of repeated lipopolysaccharide treatment and aging on hippocampal function and biomarkers of hippocampal senescence., Mol. Neurobiol., 57, 4045, 10.1007/s12035-020-02008-y · DOI
  3. Bean, 2014, Estrogen receptors, the hippocampus, and memory., Neuroscientist, 20, 534, 10.1177/1073858413519865 · DOI
  4. Bean, 2015, Re-Opening the critical window for estrogen therapy., J. Neurosci., 35, 16077, 10.1523/JNEUROSCI.1890-15.2015 · DOI
  5. Beiko, 2004, Contribution of sex differences in the acute stress response to sex differences in water maze performance in the rat., Behav. Brain Res., 151, 239, 10.1016/j.bbr.2003.08.019 · DOI
  6. Bell, 2009, Environmental enrichment influences survival rate and enhances exploration and learning but produces variable responses to the radial maze in old rats., Dev. Psychobiol., 51, 564, 10.1002/dev.20394 · DOI
  7. Belviranli, 2012, Age and sex affect spatial and emotional behaviors in rats: The role of repeated elevated plus maze test., Neuroscience, 227, 1, 10.1016/j.neuroscience.2012.09.036 · DOI
  8. Bohacek, 2015, Hippocampal gene expression induced by cold swim stress depends on sex and handling., Psychoneuroendocrinology, 52, 1, 10.1016/j.psyneuen.2014.10.026 · DOI
  9. Budamagunta, 2023, Effect of peripheral cellular senescence on brain aging and cognitive decline., Aging Cell, 22, 10.1111/acel.13817 · DOI
  10. Budamagunta, 2024, Senolytic treatment alleviates doxorubicin-induced chemobrain., Aging Cell, 23, 10.1111/acel.14037 · DOI
  11. Camell, 2021, Senolytics reduce coronavirus-related mortality in old mice., Science, 373, 10.1126/science.abe4832 · DOI · Paper page
  12. Carter, 2009, Influence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity., J. Gerontol. A Biol. Sci. Med. Sci., 64, 850, 10.1093/gerona/glp060 · DOI
  13. Casaletto, 2019, Cognitive aging is not created equally: Differentiating unique cognitive phenotypes in “normal” adults., Neurobiol. Aging, 77, 13, 10.1016/j.neurobiolaging.2019.01.007 · DOI
  14. Casaletto, 2020, Sexual dimorphism of physical activity on cognitive aging: Role of immune functioning., Brain Behav. Immun., 88, 699, 10.1016/j.bbi.2020.05.014 · DOI
  15. Chan, 2012, Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis., Clin. Cancer Res., 18, 3580, 10.1158/1078-0432.CCR-11-3359 · DOI
  16. Chaouloff, 1997, Anxiety- and activity-related effects of diazepam and chlordiazepoxide in the rat light/dark and dark/light tests., Behav. Brain Res., 85, 27, 10.1016/s0166-4328(96)00160-x · DOI
  17. Colettis, 2022, Differences in learning and memory between middle-aged female and male rats., Learn. Mem., 29, 120, 10.1101/lm.053578.122 · DOI
  18. Cui, 2009, Comparison of lifelong and late life exercise on oxidative stress in the cerebellum., Neurobiol. Aging, 30, 903, 10.1016/j.neurobiolaging.2007.09.005 · DOI
  19. Domonkos, 2017, Sex differences and sex hormones in anxiety-like behavior of aging rats., Horm. Behav., 93, 159, 10.1016/j.yhbeh.2017.05.019 · DOI
  20. Eliot, 2023, Why and how to account for sex and gender in brain and behavioral research., J. Neurosci., 43, 6344, 10.1523/JNEUROSCI.0020-23.2023 · DOI
  21. Elmarzouki, 2014, Effects of cold exposure on behavioral and electrophysiological parameters related with hippocampal function in rats., Front. Cell. Neurosci., 8, 10.3389/fncel.2014.00253 · DOI
  22. Faubion, 2020, Effect of menopausal hormone therapy on proteins associated with senescence and inflammation., Physiol. Rep., 8, 10.14814/phy2.14535 · DOI
  23. Febo, 2020, Longitudinal characterization and biomarkers of age and sex differences in the decline of spatial memory., Front. Aging Neurosci., 12, 10.3389/fnagi.2020.00034 · DOI
  24. Foster, 1999, Involvement of hippocampal synaptic plasticity in age-related memory decline., Brain Res. Brain Res. Rev., 30, 236, 10.1016/S0165-0173(99)00017-X · DOI
  25. Foster, 2005, Interaction of rapid signal transduction cascades and gene expression in mediating estrogen effects on memory over the life span., Front. Neuroendocrinol., 26, 51, 10.1016/j.yfrne.2005.04.004 · DOI
  26. Foster, 2012, Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity., Prog. Neurobiol., 96, 283, 10.1016/j.pneurobio.2012.01.007 · DOI
  27. Foster, 2007, Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats., Neurobiol. Learn. Mem., 87, 522, 10.1016/j.nlm.2006.12.009 · DOI
  28. Foster, 2003, Interaction of age and chronic estradiol replacement on memory and markers of brain aging., Neurobiol. Aging, 24, 839, 10.1016/s0197-4580(03)00014-9 · DOI
  29. Fridgeirsdottir, 2014, Escalated handling of young C57BL/6 mice results in altered Morris water maze performance., Ups J. Med. Sci., 119, 1, 10.3109/03009734.2013.847511 · DOI
  30. Gameiro, 2010, Changes in the immune system during menopause and aging., Front. Biosci., 2, 1299, 10.2741/e190 · DOI
  31. Garbarino, 2020, A head-to-head comparison between senolytic therapies, dasatinib plus quercetin and fisetin, indicates sex- and genotype-specific differences in translationally relevant outcomes., Alzheimers Dement., 16, 10.1002/alz.047607 · DOI
  32. Guidi, 2012, Behavioral model for assessing cognitive decline., Methods Mol. Biol., 829, 145, 10.1007/978-1-61779-458-2_8 · DOI
  33. Guidi, 2014, Assessing the emergence and reliability of cognitive decline over the life span in Fisher 344 rats using the spatial water maze., Front. Aging Neurosci., 6, 10.3389/fnagi.2014.00002 · DOI
  34. Ishisaka, 2014, Specific localization of quercetin-3-O-glucuronide in human brain., Arch. Biochem. Biophys., 557, 11, 10.1016/j.abb.2014.05.025 · DOI
  35. Jefferson, 2007, Inflammatory biomarkers are associated with total brain volume: The Framingham Heart Study., Neurology, 68, 1032, 10.1212/01.wnl.0000257815.20548.df · DOI
  36. Khaleghi, 2021, Estrogen attenuates physical and psychological stress-induced cognitive impairments in ovariectomized rats., Brain Behav., 11, 10.1002/brb3.2139 · DOI
  37. Knufinke, 2023, Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: A systematic review., Front. Aging, 4, 10.3389/fragi.2023.1172789 · DOI
  38. Kumar, 2009, Susceptibility to calcium dysregulation during brain aging., Front. Aging Neurosci., 1, 10.3389/neuro.24.002.2009 · DOI
  39. Kumar, 2007, Neurophysiology of old neurons and synapses, Brain Aging: Models, Methods, and Mechanisms
  40. Kumar, 2013, Linking redox regulation of NMDAR synaptic function to cognitive decline during aging., J. Neurosci., 33, 15710, 10.1523/JNEUROSCI.2176-13.2013 · DOI
  41. Kumar, 2018, Nonsteroidal anti-inflammatory drug, indomethacin improves spatial memory and NMDA receptor function in aged animals., Neurobiol. Aging, 70, 184, 10.1016/j.neurobiolaging.2018.06.026 · DOI
  42. Kumar, 2012, Influence of late-life exposure to environmental enrichment or exercise on hippocampal function and CA1 senescent physiology., Neurobiol. Aging, 33, 10.1016/j.neurobiolaging.2011.06.023 · DOI
  43. Leite-Almeida, 2009, The impact of age on emotional and cognitive behaviours triggered by experimental neuropathy in rats., Pain, 144, 57, 10.1016/j.pain.2009.02.024 · DOI
  44. Liu, 2016, Estrogen receptor alpha inhibits senescence-like phenotype and facilitates transformation induced by oncogenic ras in human mammary epithelial cells., Oncotarget, 7, 39097, 10.18632/oncotarget.9772 · DOI
  45. Lundervold, 2014, Age and sex related changes in episodic memory function in middle aged and older adults., Scand. J. Psychol., 55, 225, 10.1111/sjop.12114 · DOI
  46. Mabry, 1996, Age and stress history effects on spatial performance in a swim task in Fischer-344 rats., Neurobiol. Learn. Mem., 66, 1, 10.1006/nlme.1996.0038 · DOI
  47. Marcondes, 2002, Determination of the estrous cycle phases of rats: Some helpful considerations., Braz. J. Biol., 62, 609, 10.1590/s1519-69842002000400008 · DOI
  48. McQuail, 2020, Cognitive reserve in model systems for mechanistic discovery: The importance of longitudinal studies., Front. Aging Neurosci., 12, 10.3389/fnagi.2020.607685 · DOI
  49. Mehdipour, 2021, Plasma dilution improves cognition and attenuates neuroinflammation in old mice., Geroscience, 43, 1, 10.1007/s11357-020-00297-8 · DOI · Paper page
  50. Monleon, 2002, Chronic administration of fluoxetine impairs inhibitory avoidance in male but not female mice., Behav. Brain Res., 136, 483, 10.1016/S0166-4328(02)00194-8 · DOI
  51. Muralidharan, 2022, Long-term male-specific chronic pain via telomere- and p53-mediated spinal cord cellular senescence., J. Clin. Investig., 132, 10.1172/JCI151817 · DOI
  52. Ng, 2022, Evidence of sex differences in cellular senescence., Neurobiol. Aging, 120, 88, 10.1016/j.neurobiolaging.2022.08.014 · DOI
  53. Novais, 2021, Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice., Nat. Commun., 12, 10.1038/s41467-021-25453-2 · DOI · Paper page
  54. Nyberg, 2019, Successful memory aging., Annu. Rev. Psychol., 70, 219, 10.1146/annurev-psych-010418-103052 · DOI
  55. Olaya, 2017, Trajectories of verbal episodic memory in middle-aged and older adults: Evidence from the English Longitudinal Study of Ageing., J. Am. Geriatr. Soc., 65, 1274, 10.1111/jgs.14789 · DOI
  56. Perrot-Sinal, 1996, Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training., Behav. Neurosci., 110, 1309, 10.1037//0735-7044.110.6.1309 · DOI
  57. Polcz, 2023, Sex, sepsis and the brain: Defining the role of sexual dimorphism on neurocognitive outcomes after infection., Clin. Sci., 137, 963, 10.1042/CS20220555 · DOI
  58. Porkka, 2008, Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia., Blood, 112, 1005, 10.1182/blood-2008-02-140665 · DOI · Paper page
  59. Rajab, 2014, Sex differences in learning and memory following short-term dietary restriction in the rat., Int. J. Dev. Neurosci., 36, 74, 10.1016/j.ijdevneu.2014.05.011 · DOI
  60. Rentz, 2017, Sex differences in episodic memory in early midlife: Impact of reproductive aging., Menopause, 24, 400, 10.1097/GME.0000000000000771 · DOI
  61. Scheinert, 2015, Some hormone, cytokine and chemokine levels that change across lifespan vary by cognitive status in male Fischer 344 rats., Brain Behav. Immun., 49, 216, 10.1016/j.bbi.2015.06.005 · DOI
  62. Schmidt, 2016, Associations between serum inflammatory markers and hippocampal volume in a community sample., J. Am. Geriatr. Soc., 64, 1823, 10.1111/jgs.14283 · DOI
  63. Schwab, 2022, Neurons and glial cells acquire a senescent signature after repeated mild traumatic brain injury in a sex-dependent manner., Front. Neurosci., 16, 10.3389/fnins.2022.1027116 · DOI
  64. Sensini, 2020, The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific., Sci. Rep., 10, 10.1038/s41598-020-74279-3 · DOI
  65. Smith, 2020, Hippocampal subregion transcriptomic profiles reflect strategy selection during cognitive aging., J. Neurosci., 40, 4888, 10.1523/JNEUROSCI.2944-19.2020 · DOI
  66. Turturro, 1999, Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program., J. Gerontol. A Biol. Sci. Med. Sci., 54, B492, 10.1093/gerona/54.11.b492 · DOI
  67. Walker, 2019, Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study., Neurology, 92, e1256, 10.1212/WNL.0000000000007094 · DOI · Paper page
  68. Warren, 2000, Sex differences and estropausal phase effects on water maze performance in aged rats., Neurobiol. Learn. Mem., 74, 229, 10.1006/nlme.1999.3948 · DOI
  69. Yamaguchi, 2012, Finding a Panacea among combination cancer therapies., Cancer Res., 72, 18, 10.1158/0008-5472.CAN-11-3091 · DOI
  70. Yousefzadeh, 2020, Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice., Aging Cell, 19, 10.1111/acel.13094 · DOI · Paper page
  71. Zhou, 2011, Altered behavior in experimental cortical dysplasia., Epilepsia, 52, 2293, 10.1111/j.1528-1167.2011.03267.x · DOI
  72. Zhu, 2016, Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors., Aging Cell, 15, 428, 10.1111/acel.12445 · DOI · Paper page
  73. Zorzo, 2023, Are there sex differences in spatial reference memory in the Morris water maze? A large-sample experimental study., Learn. Behav., 10.3758/s13420-023-00598-w · DOI

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Metadata

Authors
Rani, A., Bean, L., Budamagunta, V., Kumar, A., & Foster, T. C.
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2024-05-15
Volume
16
ISSN
1663-4365
DOI
10.3389/fnagi.2024.1384554
PMC
PMC11133672
Cited by
16
References
7
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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