Hippocampal metabolic profile during epileptogenesis in the pilocarpine model of epilepsy Letícia Meier, Estevan Bruginski, Joseane Righes Marafiga, Letícia Barbieri Caus, Mayara Vendramin Pasquetti, et al. Biomedical Chromatography, 2024 Temporal lobe epilepsy (TLE) is a common form of refractory epilepsy in adulthood. The metabolic profile of epileptogenesis is still poorly investigated. Elucidation of such a metabolic profile using animal models of epilepsy could help identify new metabolites and pathways involved in the mechanisms of epileptogenesis process. In this study, we evaluated the metabolic profile during the epileptogenesis periods. Using a pilocarpine model of epilepsy, we analyzed the global metabolic profile of hippocampal extracts by untargeted metabolomics based on ultra‐performance liquid chromatography–high‐resolution mass spectrometry, at three time points (3 h, 1 week, and 2 weeks) after status epilepticus (SE) induction. We demonstrated that epileptogenesis periods presented different hippocampal metabolic profiles, including alterations of metabolic pathways of amino acids and lipid metabolism. Six putative metabolites (tryptophan, N‐acetylornithine, N‐acetyl‐L‐aspartate, glutamine, adenosine, and cholesterol) showed significant different levels during epileptogenesis compared to their respective controls. These putative metabolites could be associated with the imbalance of neurotransmitters, mitochondrial dysfunction, and cell loss observed during both epileptogenesis and epilepsy. With these findings, we provided an overview of hippocampal metabolic profiles during different stages of epileptogenesis that could help investigate pathways and respective metabolites as predictive tools in epilepsy.
Routine regularity during a global pandemic: Impact on mental health outcomes and influence of chronotype Natividade de Sá Couto-Pereira, Adile Nexha, Rogério Boff Borges, Guilherme Rodriguez Amando, Ana Paula Francisco, et al. Chronobiology International, 2024 Among the public health recommendations for supporting mental health during the COVID-19 pandemic, many strategies had an impact on biological rhythms, like sleep hygiene, physical exercise and healthy eating habits. Considering the known relationship between circadian organization and mental health, our aim was to test the association between behavioral regularity and mental health, and its interaction with chronotype, in a large sample surveyed in Brazil. We collected longitudinal data using online questionnaires that assessed sociodemographic characteristics, behavioral routines, mental health (PHQ-9, GAD-7, WHO-5 scales), and chronotype estimation based on midpoint of sleep on free days - MSF (μMCTQ), in a sample of 1390 participants (81% females). We computed a Routine Regularity Score (RRS) that reflects regularity across four behaviors: sleep, eating, working, exercising. There was a strong negative association between RRS and the severity of anxiety and depressive symptoms (GAD-7 and PHQ-9 scores), which was weaker among participants with late MSF, and a strong positive association with well-being (WHO-5 scores). RRS was a mediator of the MSF-mental health association and a predictor of mental health states. This study provides empirical evidence that maintaining behavioral routines during times of hardship may serve as tools to alleviate the negative impact on mental health.
GABAergic synaptic transmission and cortical oscillation patterns in the primary somatosensory area of a valproic acid rat model of autism spectrum disorder Mellanie Fontes‐Dutra, Joseane Righes Marafiga, Júlio Santos‐Terra, Iohanna Deckmann, Gustavo Brum Schwingel, et al. European Journal of Neuroscience, 2023 Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction associated with repetitive or stereotyped behaviour. Prenatal valproic acid (VPA) exposure in rodents is a commonly used model of ASD. Resveratrol (RSV) has been shown to prevent interneuronal and behavioural impairments in the VPA model. We investigated the effects of prenatal VPA exposure and RSV on the GABAergic synaptic transmission, brain oscillations and on the genic expression of interneuron‐associated transcription factor LHX6 in the primary somatosensory area (PSSA). Prenatal VPA exposure decreased the sIPSC and mIPSC frequencies and the sIPSC decay kinetics onto layers 4/5 pyramidal cells of PSSA. About 40% of VPA animals exhibited absence‐like spike–wave discharge (SWD) events associated with behaviour arrest and increased power spectrum density of delta, beta and gamma cortical oscillations. VPA animals had reduced LHX6 expression in PSSA, but VPA animals treated with RSV had no changes on synaptic inhibition or LHX6 expression in the PSSA. SWD events associated with behaviour arrest and the abnormal increment of cortical oscillations were also absent in VPA animals treated with RSV. These findings provide new venues to investigate the role of both RSV and VPA in the pathophysiology of ASD and highlight the VPA animal model as an interesting tool to investigate pathways related to the aetiology and possible future therapies to this neuropsychiatric disorder.
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