Biology subjects

Berbegal-Saez, P.

Publications and source records attributed to Berbegal-Saez, P..

4 recordsLinked to original sources

bioRxiv2024

Chronic circadian disruption in adolescent mice impairs hippocampal memory disrupting gene expression oscillations

Chronodisruption, the misalignment of internal biological systems with external environmental changes, leads to adverse health effects. Particularly, Social Jet Lag (SJL) is defined as the discrepancy between social and biological time and it exemplifies this misalignment, affecting a large part of the young population and impacting cognitive function. Despite its prevalence, our understanding of how developmental chronodisruption ultimately translates into morbidity is limited. To address this, we implemented a chronic chronodisruption protocol in adolescent mice consisting of light/dark cycle manipulation. We employed a comprehensive battery of established behavioral tests alongside an in-depth analysis of the oscillatory expression of the molecular clock and other genes involved in relevant physiological function. Our results show that chronic circadian disruption during adolescence induces impairments in short-term, social, and spatial memory without prompting anxiety-like behavior. Additionally, we report altered gene expression patterns of circadian clock genes per1, per2, cry2 and npas2 in the hypothalamus and the hippocampus. Lastly, we observed a disruption of hippocampal gene expression oscillations which may underlie the hippocampal memory impairments. Overall, this work underscores the critical role of adolescent circadian rhythms in maintaining cognitive function, the relevance of circadian control of hippocampal homeostasis, and the importance of further research into the mechanisms of chronodisruption, particularly during adolescence, to better understand its long-term implications for cognitive function and overall health.

neuroscience↗

bioRxiv2024

Irregular light schedules induce alterations on daily rhythms and gene expression in mice

Synchronization of internal biological rhythms with external light-dark cycles is crucial for proper function and survival of the organisms, however modern life often imposes irregular light exposure, disrupting these internal clocks. This study investigated the effects of short-term shifted light-dark cycles on mice rhythmicity, and whether these alterations trigger molecular or behavioral changes. We evaluated locomotor activity, different behavioral domains and gene expression in the hypothalamus and medial prefrontal cortex. Despite non prominent behavioral impairments, such as anxiety or cognitive deficits, we observed a notable simplification in the locomotor activity patterns of the mice subjected to disrupted light-dark cycles. Molecular alterations included dysregulations in oscillations of core clock genes (Cry2, Per2) and disruptions in expression of genes involved in neuroplasticity, motivation, and stress responses, including GluA1, Crhr2, and Vip in both studied brain areas. Our study reveals that even brief light cycle shifts can disrupt circadian regulation at the molecular level, despite minimal behavioral changes. This molecular-behavioral discrepancy may suggest a complex adaptive response to drastic short-term light perturbations. Understanding the complex interplay between external light cues and internal biological rhythms regulation is crucial for mitigating the negative consequences of irregular light exposure on physiological processes and overall well-being.

neuroscience↗

bioRxiv2024

Lack of rhythmicity in Bmal1 deficient mice impairs motivation towards natural stimuli.

Maintaining appropriate circadian rhythmicity is essential for coordinating the activity of biological functions in mammalian organisms. A variety of physiological and behavioral changes have been associated with disturbances of this complex clock mechanism. In the present study, we delve into the consequences of circadian arrhythmia using the Bmal1-knockout (KO) mouse line aiming to explore potential behavioral and motivational implications. We were able to identify the intricate activity patterns that define circadian disturbance in Bmal1-KO mice by utilizing a new analysis model based on entropy divergence. Alterations in locomotor activity were accompanied by disruptions of circadian expression patterns in various clock genes as revealed by gene expression analysis. Additionally, we found a dysregulated gene expression profile in Bmal1-KO mice regarding genes related to circadian control in various brain nuclei. Specifically, the ventral striatum exhibited a dysregulation in the expression levels of genes modulating reward and motivation. Further investigation revealed that BMAL1 deficient mice showed a sustained rise in motivation and seeking behavior for food and water reinforcers in the self-administration paradigm, independently of the caloric content of the reward. Together, our data reveal that disruptions in circadian rhythmicity, induced by alterations in the molecular clock, also impact the gene expression regulating the reward system. This, in turn, can lead to altered seeking behavior and motivation for natural rewards. In summary, the present study contributes to our understanding of how reward processing is under the regulation of circadian clock machinery.

neuroscience↗

bioRxiv2023

Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition

BackgroundA single usage of a drug of abuse can have lasting effects on both the brain and behavior, continuing even after the drug has been metabolized and eliminated from the body. A single dose of cocaine can abolish endocannabinoid-mediated long-term depression (eCB-LTD) in the nucleus accumbens (NAc) within 24 hours of administration. However, it is uncertain whether this altered neuroplasticity entails a behavioral deficit. MethodsOur study employed adult male mice to investigate the effects of a single dose of cocaine (20 mg/kg) on eCB-LTD, saccharin preference, and social interactions 24 hours after administration. We also examined the gene expression in components of the eCB system. The pharmacological increase of anandamide was evaluated using the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 mg/kg). ResultsAfter a single dose of cocaine, mice displayed altered plasticity, social interactions, and preference for saccharin and a reduction in mRNA levels of the anandamide-catabolizing enzyme NAPE-PLD. We discovered that the FAAH inhibitor URB597 (1 mg/kg) successfully reversed the cocaine-induced loss of eCB-LTD in the NAc and restored normal social interaction in cocaine-exposed mice, but it did not affect their saccharin preference. ConclusionsOverall, this research underlines the neuroplastic changes and subsequent behavioral alterations that occur after the initial use of cocaine, while also suggesting a potential role for anandamide in the early impairments caused by cocaine. The findings highlight the importance of understanding the mechanisms underlying the initiation of drug use and offer a potential therapeutic target.

neuroscience↗