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Age-related changes in mice behavior and the contribution of lipocalin-2

Aging causes considerable changes in the nervous system, inducing progressive and long-lasting loss of physiological integrity and synaptic plasticity, leading to impaired brain functioning. These age-related changes quite often culminate in behavioral dysfunctions, such as impaired cognition, which...

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Autores principales: Ferreira, Ana Catarina, Sousa, Nuno, Sousa, João Carlos, Marques, Fernanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164932/
https://www.ncbi.nlm.nih.gov/pubmed/37168715
http://dx.doi.org/10.3389/fnagi.2023.1179302
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author Ferreira, Ana Catarina
Sousa, Nuno
Sousa, João Carlos
Marques, Fernanda
author_facet Ferreira, Ana Catarina
Sousa, Nuno
Sousa, João Carlos
Marques, Fernanda
author_sort Ferreira, Ana Catarina
collection PubMed
description Aging causes considerable changes in the nervous system, inducing progressive and long-lasting loss of physiological integrity and synaptic plasticity, leading to impaired brain functioning. These age-related changes quite often culminate in behavioral dysfunctions, such as impaired cognition, which can ultimately result in various forms of neurodegenerative disorders. Still, little is known regarding the effects of aging on behavior. Moreover, the identification of factors involved in regenerative plasticity, in both the young and aged brain, is scarce but crucial from a regenerative point of view and for our understanding on the mechanisms that control the process of normal aging. Recently, we have identified the iron-trafficking protein lipocalin-2 (LCN2) as novel regulator of animal behavior and neuronal plasticity in the young adult brain. On the other hand, others have proposed LCN2 as a biological marker for disease progression in neurodegenerative disorders such as Alzheimer’s disease and multiple sclerosis. Still, and even though LCN2 is well accepted as a regulator of neural processes in the healthy and diseased brain, its contribution in the process of normal aging is not known. Here, we performed a broad analysis on the effects of aging in mice behavior, from young adulthood to middle and late ages (2-, 12-, and 18-months of age), and in the absence of LCN2. Significant behavioral differences between aging groups were observed in all the dimensions analyzed and, in mice deficient in LCN2, aging mainly reduced anxiety, while sustained depressive-like behavior observed at younger ages. These behavioral changes imposed by age were further accompanied by a significant decrease in cell survival and neuronal differentiation at the hippocampus. Our results provide insights into the role of LCN2 in the neurobiological processes underlying brain function and behavior attributed to age-related changes.
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spelling pubmed-101649322023-05-09 Age-related changes in mice behavior and the contribution of lipocalin-2 Ferreira, Ana Catarina Sousa, Nuno Sousa, João Carlos Marques, Fernanda Front Aging Neurosci Aging Neuroscience Aging causes considerable changes in the nervous system, inducing progressive and long-lasting loss of physiological integrity and synaptic plasticity, leading to impaired brain functioning. These age-related changes quite often culminate in behavioral dysfunctions, such as impaired cognition, which can ultimately result in various forms of neurodegenerative disorders. Still, little is known regarding the effects of aging on behavior. Moreover, the identification of factors involved in regenerative plasticity, in both the young and aged brain, is scarce but crucial from a regenerative point of view and for our understanding on the mechanisms that control the process of normal aging. Recently, we have identified the iron-trafficking protein lipocalin-2 (LCN2) as novel regulator of animal behavior and neuronal plasticity in the young adult brain. On the other hand, others have proposed LCN2 as a biological marker for disease progression in neurodegenerative disorders such as Alzheimer’s disease and multiple sclerosis. Still, and even though LCN2 is well accepted as a regulator of neural processes in the healthy and diseased brain, its contribution in the process of normal aging is not known. Here, we performed a broad analysis on the effects of aging in mice behavior, from young adulthood to middle and late ages (2-, 12-, and 18-months of age), and in the absence of LCN2. Significant behavioral differences between aging groups were observed in all the dimensions analyzed and, in mice deficient in LCN2, aging mainly reduced anxiety, while sustained depressive-like behavior observed at younger ages. These behavioral changes imposed by age were further accompanied by a significant decrease in cell survival and neuronal differentiation at the hippocampus. Our results provide insights into the role of LCN2 in the neurobiological processes underlying brain function and behavior attributed to age-related changes. Frontiers Media S.A. 2023-04-24 /pmc/articles/PMC10164932/ /pubmed/37168715 http://dx.doi.org/10.3389/fnagi.2023.1179302 Text en Copyright © 2023 Ferreira, Sousa, Sousa and Marques. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Ferreira, Ana Catarina
Sousa, Nuno
Sousa, João Carlos
Marques, Fernanda
Age-related changes in mice behavior and the contribution of lipocalin-2
title Age-related changes in mice behavior and the contribution of lipocalin-2
title_full Age-related changes in mice behavior and the contribution of lipocalin-2
title_fullStr Age-related changes in mice behavior and the contribution of lipocalin-2
title_full_unstemmed Age-related changes in mice behavior and the contribution of lipocalin-2
title_short Age-related changes in mice behavior and the contribution of lipocalin-2
title_sort age-related changes in mice behavior and the contribution of lipocalin-2
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164932/
https://www.ncbi.nlm.nih.gov/pubmed/37168715
http://dx.doi.org/10.3389/fnagi.2023.1179302
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