Sanhueza, N. | bioRxiv Science

bioRxiv2024

Age-dependent H3K9 trimethylation by dSetdb1 impairs mitochondrial UPR leading to degeneration of olfactory neurons and loss of olfactory function in Drosophila.

AbstractAging is characterized by a decline in essential sensory functions, including olfaction, which is crucial for environmental interaction and survival. This decline is often paralleled by the cellular accumulation of dysfunctional mitochondria, particularly detrimental in post-mitotic cells such as neurons. Mitochondrial stress triggers the mitochondrial unfolded protein response (UPRMT), a pathway that activates mitochondrial chaperones and antioxidant enzymes. Critical to the efficacy of the UPRMT is the cellular chromatin state, influenced by the methylation of lysine 9 on histone 3 (H3K9). While it has been observed that the UPRMT response can diminish with an increase in H3K9 methylation, its direct impact on age-related neurodegenerative processes, especially in the context of olfactory function, has not been clearly established. Using Drosophila, we demonstrate that an age-dependent increase in H3K9 trimethylation by the methyltransferase dSetdb1 reduces the activation capacity of the UPRMT in olfactory projection neurons leading to neurodegeneration and loss of olfactory function. Age-related neuronal degeneration was associated with morphological alterations in mitochondria and an increase in reactive oxygen species levels. Importantly, forced demethylation of H3K9 through knockdown of dSetdb1 in olfactory projection neurons restored the UPRMT activation capacity in aged flies, and suppressed age-related mitochondrial morphological abnormalities. This in turn prevented age-associated neuronal degeneration and rescued age-dependent loss of olfactory function. Our findings highlight the effect of age-related epigenetic changes on the response capacity of the UPRMT, impacting neuronal integrity and function. Moreover, they suggest a potential therapeutic role for UPRMT regulators in age-related neurodegeneration and loss of olfactory function.

neuroscience↗

bioRxiv2023

Behavioral Thermoregulation in Captive Fish: Molecular, Physiological, and Welfare Implications

Environmental Enrichment (EE) serves as a cornerstone in the attempt to emulate natural habitats for captive organisms. While substantial strides have been made in this field, current methodologies still grapple with discrepancies between recreated habitats and the innate conditions vital for maintaining biological homeostasis in captive species. Our study highlights the pivotal role of behavioral thermoregulation in modulating molecular and physiological outcomes in captive fish. Collective evidence suggests that enabling fish to autonomously regulate temperature confers numerous beneficial cellular and systemic effects. Specifically, introducing a thermal gradient within the EE paradigm correlated with increased survival metrics, enhanced physiological parameters, and improved welfare indices, establishing the criticality of thermoregulation in captivity. In contrast, the lack of a thermoregulatory framework resulted in the emergence of transient free radicals, a clear marker of temperature-induced oxidative stress. Persistent disruptions in free radical equilibrium, especially in uniform temperature settings, were linked to DNA damage, heightened cellular apoptosis, tissue anomalies, and metabolic deviations. In conclusion, this research underscores the significance of behavioral thermoregulation as an integral feature of EE, especially related to fish in controlled environments. Our data present key biomarkers valuable for optimizing fish welfare and highlight the necessity for sustained research into their adaptability and survival benchmarks. Such insights aim to enhance EE protocols, fortifying their efficacy in mirroring natural habitats and, in turn, advancing the welfare benchmarks of captive organisms.

physiology↗