Influence of changes in occupational status during the COVID-19 pandemic on suicidal narrative, suicide crisis syndrome, and suicidal ideation in Brazil.

This article aims to examine differences in suicidal narrative and suicide crisis syndrome symptoms, and suicidal ideation among those who maintained, lost, and gained employment or student status during the COVID-19 pandemic. It is a cross-sectional study based on an online and anonymous self-report questionnaire. Participants were recruited through social media platforms between November 2020 and October 2021. Changes in occupational status were assessed in 2,259 individuals. The sample was divided into four groups according to work (full-time/part-time) and study status (1) maintained, (2) lost, (3) gained, and (4) unemployed. Suicide outcomes were investigated by the Suicidal Narrative Inventory, Suicide Crisis Inventory, and Columbia - Suicide Severity Rating Scale Screener version. Changes in occupational status influenced symptoms of the suicide crisis syndrome and suicidal narrative, but not suicidal ideation. Those who maintained their work, such as full-time/part-time scored lower on the total scores of the Suicidal Narrative Inventory and Suicide Crisis Inventory-2 compared to those who lost their employed status and unemployed. Our findings suggest that it is appropriate to consider changes in employed status as a mental health risk factor during pandemics.

Abbreviated Suicidal Narrative Inventory: Factor Structure, Internal Consistency, and Validity in a Brazilian Sample.

AIM: To investigate the factor structure, reliability, and validity of the Brazilian version of the Abbreviated Suicidal Narrative Inventory (SNI-38). METHODS: We used an anonymous online questionnaire of the SNI-38 and self-report measures administered between November 2020 and October 2021 in the Brazilian community. Participants were recruited through social media advertisements. Confirmatory factor analysis was carried out to test the factor structure of the SNI-38. In addition, we examined internal consistency, and convergent validity against stressful life events, the suicide crisis syndrome, suicidal ideation, and suicide attempts. RESULTS: 2660 participants were included. The eight-factor model SNI-38 had a good model fit (χ2[637] = 7,473.98, p < .001, CFI = .99, TLI = .99, RMSEA = .07, SRMR = .06); all items were significantly and positively loaded onto their respective factors (factor loadings ≥ .45). Reliability was good to high in all subscales except goal disengagement. Additionally, all subscales - except goal disengagement - were correlated positively which the suicide crisis syndrome, stressful life events, lifetime/past-month suicidal ideation, and lifetime suicide attempts. CONCLUSIONS: These findings provide preliminary support for the validity of the Brazilian version of the SNI-38, being an appropriate and valid tool for measuring suicidal narrative among Brazilian samples.

Suicide Crisis Inventory-2: factor structure, internal consistency, and validity in a Brazilian sample.

OBJECTIVE: To evaluate the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory-2 (SCI-2) among Brazilian adults. METHODS: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 Brazilian participants. Confirmatory factor analysis (CFA) was used to assess factor structure, internal consistency, convergent validity, and criterion validity by using measures such as suicidal narratives, stressful life events, suicidal ideation, and suicide attempts. RESULTS: The revised one-factor model of the SCI-2 demonstrated an adequate, although not optimal, model fit (?2[1539] = 31,442.79, p < 0.001, comparative fit index [CFI] = 0.99, Tucker-Lewis index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.09, standardized root mean residual [SRMR] = 0.05). The revised five-factor model, on the other hand, demonstrated good fit (?2[1529] = 14,174.86, p < 0.001, CFI = 1.00, TLI = 1.00, RMSEA = 0.06, SRMR = 0.04). Comparison of these two models indicated that the five-factor model had a better fit than the one-factor model. Both the total and subscale scores of the SCI-2 showed strong internal consistency and good convergent and criterion validity in relation to stressful life events, suicidal narratives (excluding the goal disengagement subscale), suicidal ideation, and suicide attempts. CONCLUSION: Our findings suggest that the Brazilian version of the SCI-2 is a valid tool for assessing symptoms of suicidal crisis syndrome.

Sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.

The present study aimed to evaluate if sepsis sensitizes behavioural and biochemical responses induced by m-amphetamine. For this, Wistar rats were submitted to the cecal ligation and puncture. After 30 days of cecal ligation and puncture procedure, the animals were submitted to a single intraperitoneal injection of saline or m-amphetamine (.25, .50, or 1.0 mg/kg). Locomotor behaviour was assessed 2 h after the administration. Interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor-α, dopamine-cAMP-regulated phosphoprotein of 32,000 kDa (DARPP-32) and neuronal calcium sensor (NCS-1) levels were evaluated in the frontal cortex, hippocampus and striatum. Also, brain-derived neurotrophic factor (BDNF), neuronal growth factor and glial-derived neurotrophic factor levels were assessed in the hippocampus. M-amphetamine alone (.25 and 1.0 mg/kg) increased rats' locomotion and exploratory behaviour compared with the Sham + Sal. Animals from the cecal ligation and puncture + m-amphetamine (.5 and/or 1.0 mg/kg) group showed an increase in locomotion, exploratory and risk-like behaviour when compared with the Sham + Saline group and with its respective Sham groups. Cecal ligation and puncture increased interleukin levels compared with the Sham + Sal. However, cecal ligation and puncture animals that received m-amphetamine (1 mg/kg) increased even more, these inflammatory parameters compared with the Sham + Sal and the cecal ligation and puncture + saline group. M-amphetamine at lower doses increased neurotrophic factors, but higher doses decreased these parameters in the brain of cecal ligation and puncture rats. M-amphetamine dose-dependently increased DARPP-32 and NCS-1 levels in cecal ligation and puncture rats in some structures. In conclusion, these results demonstrate that sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.

Abbreviated Suicidal Narrative Inventory: factor structure, internal consistency, and validity in a Brazilian sample

Objective: To test the factor structure, reliability, and validity of the Brazilian version of the Abbreviated Suicidal Narrative Inventory (SNI-38). Methods: We used an anonymous online questionnaire of the SNI-38 and self-report measures administered between November 2020 and October 2021 in the Brazilian community. Participants were recruited through social media advertisements. Confirmatory factor analysis (CFA) was performed to test the factor structure of the SNI-38. In addition, we assessed internal consistency and convergent validity against stressful life events, suicide crisis syndrome, suicidal ideation, and suicide attempts. Results: A total of 2,660 participants were included. The eight-factor model of the SNI-38 had a good model fit (χ2[637] = 7,473.98, p < 0.001, comparative fit index [CFI] = 0.99, Tucker-Lewis index [TLI] = 0.99, root mean squared error of approximation [RMSEA] = 0.07, standardized root mean residual [SRMR] = 0.06). Notably, all items were significantly and positively loaded onto their respective factors (factor loadings ≥ 0.45). The reliability of all subscales except for goal disengagement ranged from good to high. Furthermore, all subscales except goal disengagement showed positive correlations with variables such as suicide crisis syndrome, stressful life events, lifetime/past month suicidal ideation, and lifetime suicide attempts. Conclusion: These findings provide preliminary support for the validity of the Brazilian version of the SNI-38 as an appropriate, valid instrument for measuring suicidal narratives in Brazilian individuals.

Influence of changes in occupational status during the COVID-19 pandemic on suicidal narrative, suicide crisis syndrome, and suicidal ideation in Brazil / Influências das mudanças no status ocupacional durante a pandemia de COVID-19 nos sintomas da narrativa suicida, síndrome da crise suicida e ideação suicida no Brasil

Abstract This article aims to examine differences in suicidal narrative and suicide crisis syndrome symptoms, and suicidal ideation among those who maintained, lost, and gained employment or student status during the COVID-19 pandemic. It is a cross-sectional study based on an online and anonymous self-report questionnaire. Participants were recruited through social media platforms between November 2020 and October 2021. Changes in occupational status were assessed in 2,259 individuals. The sample was divided into four groups according to work (full-time/part-time) and study status (1) maintained, (2) lost, (3) gained, and (4) unemployed. Suicide outcomes were investigated by the Suicidal Narrative Inventory, Suicide Crisis Inventory, and Columbia - Suicide Severity Rating Scale Screener version. Changes in occupational status influenced symptoms of the suicide crisis syndrome and suicidal narrative, but not suicidal ideation. Those who maintained their work, such as full-time/part-time scored lower on the total scores of the Suicidal Narrative Inventory and Suicide Crisis Inventory-2 compared to those who lost their employed status and unemployed. Our findings suggest that it is appropriate to consider changes in employed status as a mental health risk factor during pandemics.

Resumo O objetivo do artigo é examinar diferenças nos sintomas da narrativa suicida e da síndrome de crise de suicídio e ideação suicida entre aqueles que mantiveram, perderam e ganharam emprego ou status educacional durante a pandemia de COVID-19. Trata-se de um estudo transversal baseado em um questionário online. Os indivíduos foram recrutados por meio de plataformas de mídia social entre novembro de 2020 e outubro de 2021. As mudanças no status ocupacional foram avaliadas em 2.259 indivíduos. A amostra foi dividida em grupos de acordo com as mudanças do status ocupacional: (1) aqueles que mantiveram, (2) aqueles que perderam, (3) aqueles que ganharam e (4) desempregados. Desfechos suicidas foram avaliados através do Inventário da Narrativa Suicida, Inventário da Crise Suicida e Columbia - Escala de Classificação da Gravidade do Suicídio. Mudanças no status ocupacional influenciaram sintomas da síndrome de crise de suicídio e narrativa suicida, mas não a ideação suicida. Aqueles que mantiveram seu emprego apresentaram menos sintomas de narrativa suicida e síndrome de crise de suicídio, comparados aos que perderam o emprego e aos desempregados. Esses achados sugerem que é apropriado considerar mudanças no status ocupacional como fator de risco para saúde mental durante pandemias.

Suicide Crisis Inventory-2: factor structure, internal consistency, and validity in a Brazilian sample

Objective: To evaluate the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory-2 (SCI-2) among Brazilian adults. Methods: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 Brazilian participants. Confirmatory factor analysis (CFA) was used to assess factor structure, internal consistency, convergent validity, and criterion validity by using measures such as suicidal narratives, stressful life events, suicidal ideation, and suicide attempts. Results: The revised one-factor model of the SCI-2 demonstrated an adequate, although not optimal, model fit (χ2[1539] = 31,442.79, p < 0.001, comparative fit index [CFI] = 0.99, Tucker-Lewis index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.09, standardized root mean residual [SRMR] = 0.05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < 0.001, CFI = 1.00, TLI = 1.00, RMSEA = 0.06, SRMR = 0.04). Comparison of these two models indicated that the five-factor model had a better fit than the one-factor model. Both the total and subscale scores of the SCI-2 showed strong internal consistency and good convergent and criterion validity in relation to stressful life events, suicidal narratives (excluding the goal disengagement subscale), suicidal ideation, and suicide attempts. Conclusion: Our findings suggest that the Brazilian version of the SCI-2 is a valid tool for assessing symptoms of suicidal crisis syndrome.

Suicide Risk Moderates the Relationship Between Stressful Life Events, the Suicidal Narrative, and the Suicide Crisis Syndrome: A Brazilian Cross-Sectional Study.

BACKGROUND: Stressful life events are associated with higher odds of suicidal thoughts and behaviors. Furthermore, stressful life events can trigger specific symptoms, including the suicidal narrative and suicide crisis syndrome, resulting in an increased risk of suicidal thoughts and behaviors. This study examined the moderating role of suicide risk in the relationship between stressful life events, the suicidal narrative, and the suicide crisis syndrome. METHODS: 2,260 adults completed an online survey recruited through advertisements on social media. The level of emotional distress was assessed through the Suicide Narrative Inventory, Suicide Crisis Inventory-2, Stressful Life Events Questionnaire, and Mini International Neuropsychiatric Interview. The PROCESS macro (Hayes) was used to analyze the moderation models. RESULTS: Stressful life events were positively correlated with the suicidal narrative and suicide crisis syndrome. The effects of stressful life events on suicidal narrative and suicide crisis syndrome were strongest when suicide risk was low and weakest when suicide risk was high. CONCLUSIONS: These findings suggest that including stressful life events as part of suicide risk assessment in general and clinical settings is critical to managing treatment for suicidal thoughts and developing adaptive coping.

Potential mechanisms of action of resveratrol in prevention and therapy for mental disorders.

There is a growing body of evidence about the potential of diet and nutrients to improve the population's mental health and the treatment of psychiatric disorders. Some studies have suggested that resveratrol has therapeutic properties in mental disorders, such as major depressive disorder, bipolar disorder, Alzheimer's disease, and autism. In addition, resveratrol is known to induce several benefits modulated by multiple synergistic pathways, which control oxidative stress, inflammation, and cell death. This review collects the currently available data from animal and human studies and discusses the potential mechanisms of action of resveratrol in prevention and therapy for psychiatric disorders.

Haloperidol alters neurotrophic factors and epigenetic parameters in an animal model of schizophrenia induced by ketamine.

This study aimed to evaluate Haloperidol's (Hal) effects on the behavioral, neurotrophic factors, and epigenetic parameters in an animal model of schizophrenia (SCZ) induced by ketamine (Ket). Injections of Ket or saline were administered intraperitoneal (once a day) between the 1st and 14th days of the experiment. Water or Hal was administered via gavage between the 8th and 14th experimental days. Thirty minutes after the last injection, the animals were subjected to behavioral analysis. The activity of DNA methyltransferase (DNMT), histone deacetylase (HDAC), and histone acetyltransferase and levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum. Ket increased the covered distance and time spent in the central area of the open field, and Hal did not reverse these behavioral alterations. Significant increases in the DNMT and HDAC activities were detected in the frontal cortex and striatum from rats that received Ket, Hal, or a combination thereof. Besides, Hal per se increased the activity of DNMT and HDAC in the hippocampus of rats. Hal per se or the association of Ket plus Hal decreased BDNF, NGF, NT-3, and GDNF, depending on the brain region and treatment regimen. The administration of Hal can alter the levels of neurotrophic factors and the activity of epigenetic enzymes, which can be a factor in the development of effect collateral in SCZ patients. However, the precise mechanisms involved in these alterations are still unclear.

Folic acid does not have an anti-manic effect but protect the brain against oxidative stress in an animal model of mania induced by ouabain.

BACKGROUND: Bipolar disorder (BD) is a complex and severe mental disorder that affects 1-3 % of the world population. Studies have suggested the involvement of oxidative stress in the physiopathology of this psychiatry disorder. Folic acid (FA), a vitamin from the B complex, is a nutraceutical that has recently been researched as a possible treatment for BD since folate is reduced in patients with the disorder. The present study aimed to evaluate the effects of lithium (Li) and FA on behavioral changes and oxidative stress parameters in an animal model of mania induced by ouabain (OUA). METHODS: Wistar rats received a single intracerebroventricular (ICV) injection of OUA or artificial cerebrospinal fluid (aCSF). From the day following ICV injection, the rats were treated for seven days with gavage injections of Li (47.5 mg/kg/mL), FA (50 mg/kg/mL), or water (1 mL/kg). On the 7th day after OUA injection, locomotor activity was measured using the open-field test. In addition, the oxidative stress parameters were evaluated in rats' frontal cortex, striatum, and hippocampus. RESULTS: OUA induced mania-like behavior and oxidative stress in rats' brains, but Li could reverse these alterations. FA did not affect behavior parameters; however, it presents an antioxidant effect on the brain structures evaluated. LIMITATIONS: The study was only evaluated male rats and ICV injection is an invasive procedure. CONCLUSION: These results indicate that even though FA has an effect against the oxidative stress induced by OUA, this effect was not strong enough to interfere with behavior parameters.

Prenatal Stress Induces Long-Term Behavioral Sex-Dependent Changes in Rats Offspring: the Role of the HPA Axis and Epigenetics.

Preclinical genetic studies have related stress early exposures with changes in gene regulatory mechanisms, including epigenetic alterations, such as modifications of DNA methylation, histone deacetylation, and histones acetylation. This study evaluates the effects of prenatal stress on the behavior, hypothalamus-pituitary-adrenal (HPA)-axis, and epigenetic parameters in stressed dams and their offspring. The rats were subjected to a protocol of chronic unpredictable mild stress on the fourteenth day of pregnancy until the birth of offspring. After birth, maternal care was evaluated for six days. Following weaning, the locomotor and depressive-like behaviors of the dams and their offspring (60 days old) were assessed. The HPA axis parameters were evaluated in serum from dams and offspring, and epigenetic parameters (histone acetyltransferase (HAT), histone deacetylase (HDAC), DNA methyltransferase (DNMT) activities, and the levels of histone H3 acetylated at lysine residue 9 (H3K9ac) and histone 3 acetylated at lysine residue 14 (H3K14ac)) were assessed in dams' and offspring' brains. Prenatal stress did not significantly influence maternal care; however, it induced manic behavior in female offspring. These behavioral alterations in the offspring were accompanied by hyperactivity of the HPA-axis, epigenetic adaptations in the activity of HDAC and DNMT, and acetylation in the histones H3K9 and H3K14. In addition, the prenatal stressed female offspring showed increased levels of ACTH compared to their male counterpart. Our findings reinforce the impact of prenatal stress on behavior, stress response, and epigenetic profile of offspring.

Imipramine Can Be Effective on Depressive-Like Behaviors, but Not on Neurotrophic Factor Levels in an Animal Model for Bipolar Disorder Induced by Ouabain.

INTRODUCTION: Despite possible risks of mania switching with the long-term use of antidepressants in patients with bipolar disorder (BD), these drugs may help in depressive episodes. Alterations in neurotrophic factor levels seem to be involved in the pathophysiology of BD. The present study aimed to evaluate the effect of acute treatment of imipramine on behavior and neurotrophic levels in rats submitted to the animal model for BD induced by ouabain. METHODS: Wistar rats received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid or ouabain (10-3 M). Following the ICV administration, the rats were treated for 14 days with saline (NaCl 0.9%, i.p.), lithium (47.5 mg/kg, i.p.), or valproate (200 mg/kg, i.p.). On the 13th and 14th days of treatment, the animals received an additional injection of saline or imipramine (10 mg/kg, i.p.). Behavior tests were evaluated 7 and 14 days after ICV injection. Adrenal gland weight and concentrations of ACTH were evaluated. Levels of neurotrophins BDNF, NGF, NT-3, and GDNF were measured in the frontal cortex and hippocampus by ELISA test. RESULTS: The administration of ouabain induced mania- and depressive-like behavior in the animals 7 and 14 days after ICV, respectively. The treatment with lithium and valproate reversed the mania-like behavior. All treatments were able to reverse most of the depressive-like behaviors induced by ouabain. Moreover, ouabain increased HPA-axis parameters in serum and decreased the neurotrophin levels in the frontal cortex and hippocampus. All treatments, except imipramine, reversed these alterations. CONCLUSION: It can be suggested that acute administration of imipramine alone can be effective on depressive-like symptoms but not on neurotrophic factor alterations present in BD.

Enriched environment causes epigenetic changes in hippocampus and improves long-term cognitive function in sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory response. Environmental conditions play an important role in various pathologies depending on the stimulus it presents. A standard environment condition (SE) may offer reduced sensory and cognitive stimulation, but an enriched environment improves spatial learning, prevents cognitive deficits induced by disease stress, and is an important modulator of epigenetic enzymes. The study evaluated the epigenetic alterations and the effects of the environmental enrichment (EE) protocol in the brain of animals submitted to sepsis by cecal ligation and perforation (CLP). Male Wistar rats were divided into sham and CLP at 24 h, 72 h, 10 days and 30 days after sepsis. Other male Wistar rats were distributed in a SE or in EE for forty-five days. Behavioral tests, analysis of epigenetic enzymes:histone acetylase (HAT), histone deacetylase (HDAC) and DNA methyltransferase (DNMT), biochemical and synaptic plasticity analyzes were performed. An increase in HDAC and DNMT activities was observed at 72 h, 10 days and 30 days. There was a positive correlation between epigenetic enzymes DNMT and HDAC 24 h, 10 days and 30 days. After EE, HDAC and DNMT enzyme activity decreased, cognitive impairment was reversed, IL1-ß levels decreased and there was an increase in PSD-95 levels in the hippocampus. Interventions in environmental conditions can modulate the outcomes of long-term cognitive consequences associated with sepsis, supporting the idea of the potential benefits of EE.

Environmental enrichment improves lifelong persistent behavioral and epigenetic changes induced by early-life stress.

This study aimed to evaluate the effects of environmental enrichment (EE) in Wistar rats subjected to maternal deprivation (MD). MD was performed in the first post-natal days (PND) ten for 3 h/day. The groups were: control; deprived without EE; and deprived with EE. The EE was applied for 3 h/day. Forced swimming test (FST) and open field test were performed, and histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activities in the prefrontal cortex (PFC) and hippocampus were evaluated on 31, 41, and 61 PND. MD altered spontaneous locomotor activity and immobility time in FST, but the effects were sex- and developmental period dependent. In deprived females at PND 31, 41, and 61, HDAC and DNMT increased in the PFC and hippocampus. In females exposed to EE for 20 days, there was a decrease of HDAC in the hippocampus and DNMT in the PFC and hippocampus. Exposure of females to EE for 40 days can reverse HDAC and DNMT increase in all brain areas. In deprived males at PND 31, 41, and 61, HDAC and DNMT increased in the hippocampus, and in the group exposed to EE for 40 days, there was a decrease in hippocampal activity. In PFC of male deprived rats at PND 61 and EE for 40 days, there was a reduction of HDAC and DNMT. MD induced lifelong persistent behavioral and epigenetic changes, and such effects were more evident in female than male rats. EE can be considered an essential non-pharmacological strategy to treat long-term trauma-induced early life changes.

Effects of maternal folic acid supplementation on nuclear methyltransferase activity of adult rats subjected to an animal model of schizophrenia.

INTRODUCTION: Schizophrenia is considered one of the most disabling and severe human diseases worldwide. The etiology of schizophrenia is thought to be multifactorial and evidence suggests that DNA methylation can play an important role in underlying pivotal neurobiological alterations of this disorder. Some studies have demonstrated the effects of dietary supplementation as an alternative approach to the prevention of schizophrenia, including folic acid. However, no study has ever investigated the role of such supplementation in altering the DNA methylation system in the context of schizophrenia. OBJECTIVES: The present study aims to investigate the effects of maternal folic acid supplementation at different doses on nuclear methyltransferase activity of adult rat offspring subjected to an animal model schizophrenia induced by ketamine. METHODS: Adult female Wistar rats, (60 days old) received folic acid-deficient diet, control diet, or control diet plus folic acid supplementation (at 5, 10, or 50 mg/kg) during pregnancy and lactation. After reaching adulthood (60 days), the male offspring of these dams were subjected to the animal model of schizophrenia induced by 7 days of ketamine intraperitoneal injection (25 mg/kg). After the 7-day protocol, the activity of nuclear methyltransferase was evaluated in the brains of the offspring. RESULTS: Maternal folic acid supplementation at 50 mg/kg increased methyltransferase activity in the frontal cortex, while 10 mg/kg increased methyltransferase activity in the hippocampus. In the striatum of offspring treated with ketamine, maternal deficient diet, control diet, and folic acid supplementation at 5 mg/kg decreased methyltransferase activity compared to the control group. The folic acid supplementation at 10 and 50 mg/kg reversed this ketamine effect. CONCLUSIONS: Maternal FA deficiency could be related to schizophrenia pathophysiology, while FA supplementation could present a protective effect since it demonstrated persistent effects in epigenetic parameters in adult offspring.

Administration of branched-chain amino acids alters epigenetic regulatory enzymes in an animal model of Maple Syrup Urine Disease.

Maple Syrup Urine Disease (MSUD) is an autosomal recessive inherited disorder that affects the activity of the branched-chainα-keto acid dehydrogenase complex (BCDK). This deficiency on BCDK complex results in the accumulation of branched-chain amino acids (BCAA) leucine, isoleucine, valine, and their corresponding α-keto acids. Epigenetic changes can negatively affect the metabolism of BCAA. These changes are catalyzed by the epigenetic regulatory enzymes, e.g., DNA methyltransferase (DNMT), histone deacetylases (HDAC), and histone acetyltransferases (HAT). However, the impacts of BCAA administration on the activity of epigenetic regulatory enzymes in the brain of MSUD patients are still unknown. In this study, we aimed to demonstrate the impact of BCAA administration on the activity of DNMT, HDAC, and HAT in the brain structures of infant rats, an animal model of MSUD. For that, we administered a BCAA pool to infant rats for 21 days. We demonstrated that BCAA administration significantly increased the DNMT and HDAC activities in the hippocampus and striatum, but not in the cerebral cortex of MSUD infant rats. A positive correlation was observed between HDAC and DNMT activities in the hippocampus and striatum of animals exposed to BCAA injections. Our results showed that the BCAA administration could modulate epigenetic regulatory enzymes, mainly DNMT and HDAC, in the brains of infant rats. Therefore, we suggest that the increase in the activity of DNMT and HDAC in the hippocampus and striatum could partially explain the neurological impairments presented in animal models of MSUD.

Role of epigenetic regulatory enzymes in animal models of mania induced by amphetamine and paradoxical sleep deprivation.

It is known that bipolar disorder has a multifactorial aetiology where the interaction between genetic and environmental factors is responsible for its development. Because of this, epigenetics has been largely studied in psychiatric disorders. The present study aims to evaluate the effects of histone deacetylase inhibitors on epigenetic enzyme alterations in rats or mice submitted to animal models of mania induced by dextro-amphetamine or sleep deprivation, respectively. Adult male Wistar rats were subjected to 14 days of dextro-amphetamine administration, and from the eighth to the fourteenth day, the animals were treated with valproate and sodium butyrate in addition to dextro-amphetamine injections. Adult C57BL/6 mice received 7 days of valproate or sodium butyrate administration, being sleep deprived at the last 36 hr of the protocol. Locomotor and exploratory activities of rats and mice were evaluated in the open-field test, and histone deacetylase, DNA methyltransferase, and histone acetyltransferase activities were assessed in the frontal cortex, hippocampus, and striatum. Dextro-amphetamine and sleep deprivation induced hyperactivity and increased histone deacetylase and DNA methyltransferase activities in the animal's brain. Valproate and sodium butyrate were able to reverse hyperlocomotion induced by both animal models, as well as the alterations on histone deacetylase and DNA methyltransferase activities. There was a positive correlation between enzyme activities and number of crossings for both models. Histone deacetylase and DNA methyltransferase activities also presented a positive correlation between theirselves. These results suggest that epigenetics can play an important role in BD pathophysiology as well as in its treatment.