RESUMO
Reduction of the dendritic arbor length and the lack of dendritic spines in the pyramidal cells of the prefrontal cortex (PFC) are prevalent pathological features in schizophrenia (SZ). Neonatal ventral hippocampus lesion (NVHL) in male rats reproduces these neuronal characteristics and here we describe how this is a consequence of BDNF/TrkB pathway disruption. Moreover, COX-2 proinflammatory state, as well as Nrf-2 antioxidant impairment, triggers oxidative/nitrosative stress, which also contributes to dendritic spine impairments in the PFC. Interestingly, oxidative/nitrosative stress was also detected in the periphery of NVHL animals. Furthermore, risperidone treatment had a neurotrophic effect on the PFC and antioxidant effects on the brain and periphery of NVHL animals; these cellular effects were related to behavioral improvement. Our data highlight the link between brain development and immune response, as well as several other factors to understand mechanisms related to the pathophysiology of SZ.SIGNIFICANCE STATEMENT Prefrontal cortex dysfunction in schizophrenia can be a consequence of morphological abnormalities and oxidative/nitrosative stress, among others. Here, we detailed how impaired plasticity-related pathways and oxidative/nitrosative stress are part of the dendritic spine pathology and their modulation by atypical antipsychotic risperidone treatment in rats with neonatal ventral hippocampus lesion. Moreover, we found that animals with neonatal ventral hippocampus lesion had oxidative/nitrosative stress in the brain as well as in the peripheral blood, an important issue for the translational approaches of this model. Then, risperidone restored plasticity and reduced oxidative/nitrosative stress of prefrontal cortex pyramidal cells, and ultimately improved the behavior of lesioned animals. Moreover, risperidone had differential effects than the brain on peripheral blood oxidative/nitrosative stress.
Assuntos
Antipsicóticos/uso terapêutico , Atrofia/tratamento farmacológico , Hipocampo/patologia , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Risperidona/uso terapêutico , Animais , Antipsicóticos/farmacologia , Atrofia/metabolismo , Atrofia/patologia , Espinhas Dendríticas/metabolismo , Hipocampo/metabolismo , Masculino , Córtex Pré-Frontal/metabolismo , Ratos , Risperidona/farmacologiaRESUMO
Objective: Coronavirus disease 2019 (COVID-19) has impacted mental health worldwide, and suicide can be a serious outcome of this. Thus, suicide characteristics were examined before and during the COVID-19 pandemic in Mexico City. Methods: This is a retrospective study including all Mexico City residents who had a coroner's record with a cause of death of intentional self-harm (ICD-10) from January 2016 to December 2021. Results: From 2016 to 2021, 3636 people committed suicide, of which 2869 were males (78.9%) and 767 females (21.1%). From 2016 to 2019 the suicide rate remained constant (â¼6 per 100000) and dramatically increased in 2020 (10.45 per 100,000), to return to the levels of the previous year in 2021 (6.95 per 100000). The suicide rate in 2020 specifically increased from January to June (COVID-19 outbreak) in all age groups. Moreover, every year young people (15-24 years) have the maximum suicide rate and depression was the main suicide etiology. Conclusion: The COVID-19 pandemic outbreak increased the suicide rate, regardless of age, but suicide prevalence was higher in males and young people, regardless of the COVID-19 pandemic. These findings confirm that suicide is a complex and multifactorial problem and will allow the establishment of new guidelines for prevention and care strategies.
RESUMO
Second-generation antipsychotics are the drugs of choice for the treatment of neurodevelopmental-related mental diseases such as schizophrenia. Despite the effectiveness of these drugs to ameliorate some of the symptoms of schizophrenia, specifically the positive ones, the mechanisms beyond their antipsychotic effect are still poorly understood. Second-generation antipsychotics are reported to have anti-inflammatory, antioxidant and neuroplastic properties. Using the neonatal ventral hippocampus lesion (nVHL) in the rat, an accepted schizophrenia-related model, we evaluated the effect of the second-generation antipsychotic olanzapine (OLZ) in the behavioral, neuroplastic, and neuroinflammatory alterations exhibited in the nVHL animals. OLZ corrected the hyperlocomotion and impaired working memory of the nVHL rats but failed to enhance social behavior disturbances of these animals. In the prefrontal cortex (PFC), OLZ restored the pyramidal cell structural plasticity in the nVHL rats, enhancing the dendritic arbor length, the spinogenesis and the proportion of mature spines. Moreover, OLZ attenuated astrogliosis as well as some pro-inflammatory, oxidative stress, and apoptosis-related molecules in the PFC. These findings reinforce the evidence of anti-inflammatory, antioxidant, and neurotrophic mechanisms of second-generation antipsychotics in the nVHL schizophrenia-related model, which allows for the possibility of developing more specific drugs for this disorder and thus avoiding the side effects of current schizophrenia treatments.
Assuntos
Antipsicóticos , Esquizofrenia , Ratos , Animais , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Olanzapina/farmacologia , Olanzapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antioxidantes/farmacologia , Ratos Sprague-Dawley , Córtex Pré-Frontal , Hipocampo , Plasticidade Neuronal , Modelos Animais de DoençasRESUMO
Brain aging is a widely studied process, but due to its complexity, much of its progress is unknown. There are many studies linking memory loss and reduced interneuronal communication with brain aging. However, only a few studies compare young and old animals. In the present study, in male rats aged 3, 6, and 18 months, we analyzed the locomotor activity and also short and long-term memory using the novel object recognition test (NORT), in addition to evaluating the dendritic length and the number of dendritic spines in the prefrontal cortex (PFC) and in the CA1, CA3 and DG regions of the dorsal hippocampus using Golgi-Cox staining. We also analyzed the types of dendritic spines in the aforementioned regions. 6- and 18-month old animals showed a reduction in locomotor activity, while long-term memory deficit was observed in 18-month old rats. At 18 months old, the dendritic length was reduced in all the studied regions. The dendritic spine number was also reduced in layer 5 of the PFC, and the CA1 and CA3 of the hippocampus. The dynamics of dendritic spines changed with age, with a reduction of the mushroom spines in all the studied regions, with an increase of the stubby spines in all the studied regions except from the CA3 region, that showed a reduction. Our data suggest that age causes changes in behavior, which may be the result of morphological changes at the dendrite level, both in their length and in the dynamics of their spines.