08.12.2023 – 5min

Exploring Cognitive Aging: Insights from different Studies in Rodent Models Using the IntelliCage System

Life expectancy has increased greatly over the last decades, but it has been associated with a progressive rise in the incidence of age-related diseases, including neurodegeneration and dementia, which interfere with the quality of life. Aging is a multi-factorial degenerative process that strongly impacts the endocrinology and biochemistry of the brain.

The IntelliCage is a fully automated home-cage system to investigate individual cognitive decline in groups of rodents over long time periods, repeatedly in longitudinal studies and is therefore an ideal tool to study aging in animal models (Kyrik et al. 2020). Aged rodents and protecting effects of compounds on age-dependent memory decline have been studied very successfully in the IntelliCage (Mechan et al. 2009; Oizumi et al. 2020; Fischer et al. 2021).

Barranco et al (2022) reported beneficial effects of oral β-hydroxy β-methylbutyrate (HMB), a drug typically used for body composition and muscle performance, on cognitive function including working memory and electrophysiological measurements in adult and middle-aged mice and rats.

Interestingly, Barry et al (2012) observed that females are less affected by age-dependent decreases in brain weight and neurogenesis, retain exploration activity, and show better performance in spatial learning task in the IntelliCage than males. This effect is amplified in the absence of a gene that leads to reduced oxidative stress accompanied by decreased incidence of age-related pathologies and reduced signs of behavioral aging.

Using fully automated test batteries in the IntelliCage, Albuquerque et al (2013) demonstrated that aged mice with neuropathic pain, had a long maintenance of aversive memory suggesting a negative alliance and possibly mutual aggravation of chronic neuropathic pain and aversive memory. Furthermore, postoperative cognitive dysfunction (POCD) is a serious complication in particular in the elderly population. Very recently, Li et al (2023) used 18 – 20 months old rats performing a spatial learning task and splenectomy to investigate POCD in the IntelliCage and the Morris water maze. In addition, they describe a potential neuroprotective mechanism of Maresin1 by inhibition of hippocampal neuroinflammation.

Taken together, these studies suggest that the IntelliCage is a very potent tool to study healthy aging in rodent models.

References:

Albuquerque, B., Häussler, A., Vannoni, E., Wolfer, D.P., and Tegeder, I. (2013). Learning and memory with neuropathic pain: impact of old age and progranulin deficiency. Frontiers in Behavioral Neuroscience 7. doi: 10.3389/fnbeh.2013.00174.

Barranco, A., Garcia, L., Gruart, A., Delgado-Garcia, J.M., Rueda, R., and Ramirez, M. (2022). Effects of β-Hydroxy β-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents. Nutrients 14(5), 1090. doi:10.3390/nu14051090.

Berry, A., Amrein, I., Nötzli, S., Lazic, S.E., Bellisario, V., Giorgio, M., et al. (2012). Sustained hippocampal neurogenesis in females is amplified in P66Shc−/− mice: An animal model of healthy aging. Hippocampus 22(12), 2249-2259. doi: 10.1002/hipo.22042.

Fischer, C., Endle, H., Schumann, L., Wilken-Schmitz, A., Kaiser, J., Gerber, S., et al. (2020). Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2. Cellular and Molecular Life Sciences. doi: 10.1007/s00018-020-03553-4.

Kiryk, A., Janusz, A., Zglinicki, B., Turkes, E., Knapska, E., Konopka, W., et al. (2020). IntelliCage as a tool for measuring mouse behavior – 20 years perspective. Behavioural Brain Research 388. doi: ARTN 11262010.1016/j.bbr.2020.112620.

Li, X., Gao, Y., Han, X., Tang, S., Li, N., Liu, X., et al. (2023). Maresin1 ameliorates postoperative cognitive dysfunction in aged rats by potentially regulating the NF-kappaB pathway to inhibit astrocyte activation. Exp Gerontol 176, 112168. doi10.1016/j.exger.2023.112168.

Mechan, A.O., Wyss, A., Rieger, H., and Mohajeri, M.H. (2009). A comparison of learning and memory characteristics of young and middle-aged wild-type mice in the IntelliCage. Journal of Neuroscience Methods 180(1), 43-51. doi: 10.1016/j.jneumeth.2009.02.018.

Oizumi, H., Miyazaki, S., Tabuchi, M., Endo, T., Omiya, Y., and Mizoguchi, K. (2020). Kamikihito Enhances Cognitive Functions and Reward-Related Behaviors of Aged C57BL/6J Mice in an Automated Behavioral Assay System. Frontiers in Pharmacology 11, 1037. doi: 10.3389/fphar.2020.01037.

Life expectancy has increased greatly over the last decades, but it has been associated with a progressive rise in the incidence of age-related diseases, including neurodegeneration and dementia, which interfere with the quality of life. Aging is a multi-factorial degenerative process that strongly impacts the endocrinology and biochemistry of the brain.

The IntelliCage is a fully automated home-cage system to investigate individual cognitive decline in groups of rodents over long time periods, repeatedly in longitudinal studies and is therefore an ideal tool to study aging in animal models (Kyrik et al. 2020). Aged rodents and protecting effects of compounds on age-dependent memory decline have been studied very successfully in the IntelliCage (Mechan et al. 2009; Oizumi et al. 2020; Fischer et al. 2021).

Barranco et al (2022) reported beneficial effects of oral β-hydroxy β-methylbutyrate (HMB), a drug typically used for body composition and muscle performance, on cognitive function including working memory and electrophysiological measurements in adult and middle-aged mice and rats.

Interestingly, Barry et al (2012) observed that females are less affected by age-dependent decreases in brain weight and neurogenesis, retain exploration activity, and show better performance in spatial learning task in the IntelliCage than males. This effect is amplified in the absence of a gene that leads to reduced oxidative stress accompanied by decreased incidence of age-related pathologies and reduced signs of behavioral aging.

Using fully automated test batteries in the IntelliCage, Albuquerque et al (2013) demonstrated that aged mice with neuropathic pain, had a long maintenance of aversive memory suggesting a negative alliance and possibly mutual aggravation of chronic neuropathic pain and aversive memory. Furthermore, postoperative cognitive dysfunction (POCD) is a serious complication in particular in the elderly population. Very recently, Li et al (2023) used 18 – 20 months old rats performing a spatial learning task and splenectomy to investigate POCD in the IntelliCage and the Morris water maze. In addition, they describe a potential neuroprotective mechanism of Maresin1 by inhibition of hippocampal neuroinflammation.

Taken together, these studies suggest that the IntelliCage is a very potent tool to study healthy aging in rodent models.

References:

Albuquerque, B., Häussler, A., Vannoni, E., Wolfer, D.P., and Tegeder, I. (2013). Learning and memory with neuropathic pain: impact of old age and progranulin deficiency. Frontiers in Behavioral Neuroscience 7. doi: 10.3389/fnbeh.2013.00174.

Barranco, A., Garcia, L., Gruart, A., Delgado-Garcia, J.M., Rueda, R., and Ramirez, M. (2022). Effects of β-Hydroxy β-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents. Nutrients 14(5), 1090. doi:10.3390/nu14051090.

Berry, A., Amrein, I., Nötzli, S., Lazic, S.E., Bellisario, V., Giorgio, M., et al. (2012). Sustained hippocampal neurogenesis in females is amplified in P66Shc−/− mice: An animal model of healthy aging. Hippocampus 22(12), 2249-2259. doi: 10.1002/hipo.22042.

Fischer, C., Endle, H., Schumann, L., Wilken-Schmitz, A., Kaiser, J., Gerber, S., et al. (2020). Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2. Cellular and Molecular Life Sciences. doi: 10.1007/s00018-020-03553-4.

Kiryk, A., Janusz, A., Zglinicki, B., Turkes, E., Knapska, E., Konopka, W., et al. (2020). IntelliCage as a tool for measuring mouse behavior – 20 years perspective. Behavioural Brain Research 388. doi: ARTN 11262010.1016/j.bbr.2020.112620.

Li, X., Gao, Y., Han, X., Tang, S., Li, N., Liu, X., et al. (2023). Maresin1 ameliorates postoperative cognitive dysfunction in aged rats by potentially regulating the NF-kappaB pathway to inhibit astrocyte activation. Exp Gerontol 176, 112168. doi10.1016/j.exger.2023.112168.

Mechan, A.O., Wyss, A., Rieger, H., and Mohajeri, M.H. (2009). A comparison of learning and memory characteristics of young and middle-aged wild-type mice in the IntelliCage. Journal of Neuroscience Methods 180(1), 43-51. doi: 10.1016/j.jneumeth.2009.02.018.

Oizumi, H., Miyazaki, S., Tabuchi, M., Endo, T., Omiya, Y., and Mizoguchi, K. (2020). Kamikihito Enhances Cognitive Functions and Reward-Related Behaviors of Aged C57BL/6J Mice in an Automated Behavioral Assay System. Frontiers in Pharmacology 11, 1037. doi: 10.3389/fphar.2020.01037.

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