Imagine the brain as a beautiful garden that grows and flourishes in its youth, but gradually withers and loses its vibrancy as it ages. This natural process, just like an aging garden, can lead to behavioral changes and cognitive decline in mice. However, scientists have discovered a potential key player in this aging process – a protein called lipocalin-2 (LCN2). LCN2 has been found to regulate animal behavior and synaptic plasticity in young adult mice, but its role in normal aging remains a mystery. To unravel this mystery, researchers conducted a study using mice of different ages and compared their behavior with and without LCN2. The results were striking – as the mice aged, their behavior changed significantly, with reduced anxiety and increased depressive-like behavior. Furthermore, the absence of LCN2 exacerbated these age-related behavioral changes. Additionally, the researchers discovered that aging also led to decreased cell survival and neuronal differentiation in the hippocampus, an area crucial for memory and learning. These findings shed light on the important role of LCN2 in the aging process and its impact on brain function and behavior. If you’re curious to learn more about how LCN2 and aging interact to affect mouse behavior, check out the full research article!

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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