46 research outputs found
Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats
Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice
Background: Methylphenidate (MPH) is a psychostimulant that exerts its pharmacological effects via preferential blockade of the dopamine transporter (DAT) and the norepinephrine transporter (NET), resulting in increased monoamine levels in the synapse. Clinically, methylphenidate is prescribed for the symptomatic treatment of ADHD and narcolepsy; although lately, there has been an increased incidence of its use in individuals not meeting the criteria for these disorders. MPH has also been misused as a ‘‘cognitive enhancer’ ’ and as an alternative to other psychostimulants. Here, we investigate whether chronic or acute administration of MPH in mice at either 1 mg/kg or 10 mg/kg, affects cell number and gene expression in the basal ganglia. Methodology/Principal Findings: Through the use of stereological counting methods, we observed a significant reduction (,20%) in dopamine neuron numbers in the substantia nigra pars compacta (SNpc) following chronic administration of 10 mg/kg MPH. This dosage of MPH also induced a significant increase in the number of activated microglia in the SNpc. Additionally, exposure to either 1 mg/kg or 10 mg/kg MPH increased the sensitivity of SNpc dopaminergic neurons to the parkinsonian agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Unbiased gene screening employing Affymetrix GeneChipH HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN) of mice exposed to 1 mg/kg and 10 mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2, and th in the substantia nigr
Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders
Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients
Bipolar disorder (BD) is a severe psychiatric disorder characterized by phasic changes of mood and can be associated with progressive structural brain change and cognitive decline. The numbers and sizes of glia and neurons are reduced in several brain areas, suggesting the involvement of apoptosis in the pathophysiology of BD. Because the changes in mitochondrial dynamics are closely related with the early process of apoptosis and the specific processes of apoptosis and mitochondrial dynamics in BD have not been fully elucidated, we measured the apoptotic pathway and the expression of mitochondrial fission/fusion proteins from BD patients and healthy controls. We recruited 16 patients with BD type I and sixteen well-matched healthy controls and investigated protein levels of several pro-apoptotic and anti-apoptotic factors, as well as the expression of mitochondrial fission/fusion proteins in peripheral blood mononuclear cells (PBMCs). Our results showed that the levels of the anti-apoptotic proteins Bcl-xL, survivin and Bcl-xL/Bak dimer were significantly decreased, while active caspase-3 protein levels were significantly increased in PBMCs from BD patients. Moreover, we observed the downregulation of the mitochondrial fusion-related proteins Mfn2 and Opa1 and the upregulation of the fission protein Fis1 in PBMCs from BD patients, both in terms of gene expression and protein levels. We also showed a significantly decrease in the citrate synthase activity. Finally, we found a positive correlation between Mfn2 and Opa1 with mitochondrial content markers, as well as a negative correlation between mitochondrial fission/fusion proteins and apoptotic markers. Overall, data reported here are consistent with the working hypothesis that apoptosis may contribute to cellular dysfunction, brain volume loss and progressive cognitive in BD. Moreover, we show an important relationship between mitochondrial dynamics and the cell death pathway activation in BD patients, supporting the link between mitochondrial dysfunction and the pathophysiology of BD
DNA damage in rats after treatment with methylphenidate.
Methylphenidate (MPH) is a widely prescribed psychostimulant for the treatment of attention-deficit hyperactivity disorder (ADHD). Recently, some studies have addressed the genotoxic potential of the MPH, but the results have been contradictory. Hence, the present study aimed to investigate the index of cerebral and peripheral DNA damage in young and adult rats after acute and chronic MPH exposure
Abuso de cannabis em pacientes com transtornos psiquiátricos: atualização para uma antiga evidência Cannabis abuse in patients with psychiatric disorders: an update to old evidence
OBJETIVO: Realizar uma atualização sobre o abuso de cannabis em pacientes com transtornos psiquiátricos. MÉTODO: Busca de artigos nas bases de dados eletrônicas Medline, The Cochrane Library Database, Lilacs, PubMed e SciELO, utilizando os descritores "marijuana abuse", "cannabis abuse", "psychiatric disorders" AND "mental disorders"; incluindo artigos que avaliaram ambas as exposições para abuso e dependência de cannabis e qualquer outro transtorno psiquiátrico. Foi considerado o período até dezembro de 2009. RESULTADOS: Observou-se que o abuso frequente de cannabis pode aumentar o risco para o desenvolvimento de esquizofrenia e de sintomas psicóticos crônicos, embora estes achados ainda careçam de comprovação. A cannabis parece ser uma das drogas de escolha de portadores de transtorno afetivo bipolar, sendo que é descrito que estados maníacos podem ser induzidos pelo seu consumo. O abuso de maconha também frequentemente co-ocorre em indivíduos com transtornos ansiosos, sendo que a relação de cronicidade destas condições e o consumo de maconha ainda é incerta. Para depressão ainda não existem evidências claras que apontem que o consumo de cannabis ocorre como forma de automedicação. Em indivíduos com transtornos psiquiátricos, há relatos de que o uso da cannabis pode exacerbar sintomas positivos, somar efeitos negativos no curso do transtorno, contribuir para pior adesão ao tratamento e levar a maior número de hospitalizações. CONCLUSÃO: O abuso de cannabis em pacientes com transtornos psiquiátricos como esquizofrenia, transtornos do humor e ansiosos tem impacto negativo tanto na fase aguda quanto em fases mais avançadas destas condições, embora futuros estudos avaliando estas associações ainda sejam necessários.<br>OBJECTIVE: To perform an update on cannabis abuse by patients with psychiatric disorders. METHOD: A search was performed in the electronic databases Medline, The Cochrane Library Database, Lilacs, PubMed, and SciELO, using the keywords 'marijuana abuse', 'cannabis abuse', 'psychiatric disorders', and 'mental disorders'. Articles published until December 2009, dealing with cannabis abuse and dependence in association with other psychiatric disorders were included. RESULTS: Cannabis abuse was found to be associated with increased risk for the onset of schizophrenia and chronic psychotic symptoms, although these findings require confirmation from additional research. Cannabis seems to be one of the drugs of choice of individuals with bipolar disorder, despite evidence that manic states can be induced by its use. Cannabis abuse also occurs frequently in individuals with anxiety disorders, but the relationship between the chronic nature of these conditions and the use of marijuana remains uncertain. In respect to depression, there is no clear evidence to date that depressive patients use cannabis as a form of self-medication. In individuals with psychiatric disorders, the use of cannabis has been associated with increased positive symptoms, additional negative symptoms in the course of illness, impaired treatment compliance, and more hospitalizations. CONCLUSION: The abuse of cannabis by patients with psychiatric disorders such as schizophrenia and mood and anxious disorders has a negative impact both in the acute and advanced stages of these conditions, although further investigation on this association is still necessary