Conclusions from a Behavioral Aging Study on Male and Female F2 Hybrid Mice on Age-related Behavior, Buoyancy in Water-based Tests, and an Ethical Method to Assess Lifespan

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2019 Sep 12

PMID 31509518

Citations 9

Authors

Julia Adelof

Jaime M Ross

Stanley E Lazic

Madeleine Zetterberg

John Wiseman

Malin Hernebring

Affiliations

Soon will be listed here.

Abstract

Due to strain-specific behavioral idiosyncrasies, inbred mouse strains are suboptimal research models for behavioral aging studies. The aim of this study is to determine age-related behavioral changes of F2 hybrid C57BL/6NxBALB/c male and female mice. Lifespan was followed (n=48, n=51) and cohorts of mature adult (7 months), middle-aged (15 months), and old mice (22 months of age; n=7-12 per group) were assessed regarding open-field activity, exploration, passive avoidance learning/memory, and depressive-like behavior. We found that both males and females demonstrated decreased exploratory behavior with age, while memory and depressive-like behavior were maintained. Females exhibited enhanced depressive-like behavior compared to males; however, a correlation between fat mass and swimming activity in the test directly accounted for 30-46% of this behavioral sex difference. In addition, we suggest a method to qualitatively estimate natural lifespan from survival analyses in which animals with signs of pain or severe disease are euthanized. This is, to our knowledge, the first behavioral study to consider both sex and aging in hybrid mice. We here define decreased exploratory behavior as a conserved hallmark of aging independent of sex, highlight the effect of buoyancy in water tests, and provide a method to assay lifespan with reduced animal suffering.

Citing Articles

Model of Accelerated Aging in CB6F2 Mice Induced by Ionizing Radiation.

Yakunchikova E, Yurova M, Drachyov I, Radetskaya E, Altukhov K, Semenov A Bull Exp Biol Med. 2024; 177(3):363-367.

PMID: 39126549 DOI: 10.1007/s10517-024-06190-0.

The Effect of Omega-3 Fatty Acid Supplementation and Exercise on Locomotor Activity, Exploratory Activity, and Anxiety-Like Behavior in Adult and Aged Rats.

Gajdosova L, Katrencikova B, Borbelyova V, Muchova J Physiol Res. 2024; 73(3):461-480.

PMID: 39012176 PMC: 11299774. DOI: 10.33549/physiolres.935245.

Less spatial exploration is associated with poorer spatial memory in midlife adults.

Puthusseryppady V, Cossio D, Yu S, Rezwana F, Hegarty M, Jacobs E Front Aging Neurosci. 2024; 16:1382801.

PMID: 38919601 PMC: 11196421. DOI: 10.3389/fnagi.2024.1382801.

Cognitive Alterations in Old Mice Are Associated with Intestinal Barrier Dysfunction and Induced Toll-like Receptor 2 and 4 Signaling in Different Brain Regions.

Brandt A, Kromm F, Hernandez-Arriaga A, Martinez Sanchez I, Bozkir H, Staltner R Cells. 2023; 12(17).

PMID: 37681885 PMC: 10486476. DOI: 10.3390/cells12172153.

Molecular and histological correlates of cognitive decline across age in male C57BL/6J mice.

Britton R, Liu A, Rege S, Adams J, Akrapongpisak L, Le D Brain Behav. 2022; 12(9):e2736.

PMID: 35971662 PMC: 9480918. DOI: 10.1002/brb3.2736.

References

Crawley J . Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res. 1999; 835(1):18-26. DOI: 10.1016/s0006-8993(98)01258-x. View

Miller R, Austad S, Burke D, Chrisp C, Dysko R, Galecki A . Exotic mice as models for aging research: polemic and prospectus. Neurobiol Aging. 1999; 20(2):217-31. DOI: 10.1016/s0197-4580(99)00038-x. View

Kelly S, Ostrowski N, Wilson M . Gender differences in brain and behavior: hormonal and neural bases. Pharmacol Biochem Behav. 1999; 64(4):655-64. DOI: 10.1016/s0091-3057(99)00167-7. View

Frick K, Burlingame L, Arters J, Berger-Sweeney J . Reference memory, anxiety and estrous cyclicity in C57BL/6NIA mice are affected by age and sex. Neuroscience. 2000; 95(1):293-307. DOI: 10.1016/s0306-4522(99)00418-2. View

Roof R, Stein D . Gender differences in Morris water maze performance depend on task parameters. Physiol Behav. 2000; 68(1-2):81-6. DOI: 10.1016/s0031-9384(99)00162-6. View

Frackiewicz E, Sramek J, Cutler N . Gender differences in depression and antidepressant pharmacokinetics and adverse events. Ann Pharmacother. 2000; 34(1):80-8. DOI: 10.1345/aph.18465. View

Miller R, Nadon N . Principles of animal use for gerontological research. J Gerontol A Biol Sci Med Sci. 2000; 55(3):B117-23. PMC: 7110343. DOI: 10.1093/gerona/55.3.b117. View

Kant L, Yilmaz O, Taskiran D, Kulali B, Furedy J, Demirgoren S . Sexually dimorphic cognitive style, female sex hormones, and cortical nitric oxide. Physiol Behav. 2001; 71(3-4):277-87. DOI: 10.1016/s0031-9384(00)00327-9. View

Voikar V, Koks S, Vasar E, Rauvala H . Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies. Physiol Behav. 2001; 72(1-2):271-81. DOI: 10.1016/s0031-9384(00)00405-4. View

10.

Palanza P . Animal models of anxiety and depression: how are females different?. Neurosci Biobehav Rev. 2001; 25(3):219-33. DOI: 10.1016/s0149-7634(01)00010-0. View

11.

Rogers D, Peters J, Martin J, Ball S, Nicholson S, Witherden A . SHIRPA, a protocol for behavioral assessment: validation for longitudinal study of neurological dysfunction in mice. Neurosci Lett. 2001; 306(1-2):89-92. DOI: 10.1016/s0304-3940(01)01885-7. View

12.

Lucki I, Dalvi A, Mayorga A . Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl). 2001; 155(3):315-22. DOI: 10.1007/s002130100694. View

13.

Palanza P, Gioiosa L, Parmigiani S . Social stress in mice: gender differences and effects of estrous cycle and social dominance. Physiol Behav. 2001; 73(3):411-20. DOI: 10.1016/s0031-9384(01)00494-2. View

14.

Labuda C, Mellgren R, Hale R . Sex differences in the acquisition of a radial maze task in the CD-1 mouse. Physiol Behav. 2002; 76(2):213-7. DOI: 10.1016/s0031-9384(02)00713-8. View

15.

David D, Renard C, Jolliet P, Hascoet M, Bourin M . Antidepressant-like effects in various mice strains in the forced swimming test. Psychopharmacology (Berl). 2003; 166(4):373-82. DOI: 10.1007/s00213-002-1335-4. View

16.

Frick K, Gresack J . Sex differences in the behavioral response to spatial and object novelty in adult C57BL/6 mice. Behav Neurosci. 2003; 117(6):1283-91. DOI: 10.1037/0735-7044.117.6.1283. View

17.

Voikar V, Vasar E, Rauvala H . Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice: implications for phenotyping screens. Genes Brain Behav. 2004; 3(1):27-38. DOI: 10.1046/j.1601-183x.2003.0044.x. View

18.

Jonasson Z . Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data. Neurosci Biobehav Rev. 2005; 28(8):811-25. DOI: 10.1016/j.neubiorev.2004.10.006. View

19.

Benice T, Rizk A, Kohama S, Pfankuch T, Raber J . Sex-differences in age-related cognitive decline in C57BL/6J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity. Neuroscience. 2005; 137(2):413-23. DOI: 10.1016/j.neuroscience.2005.08.029. View

20.

Meziane H, Ouagazzal A, Aubert L, Wietrzych M, Krezel W . Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies. Genes Brain Behav. 2006; 6(2):192-200. DOI: 10.1111/j.1601-183X.2006.00249.x. View