RESUMO
Stress is a key factor in the development and progress of diseases. In neurodegenerative conditions, stress management can play an important role in maintaining the quality of life and the capacity to improve. Neurodegenerative diseases, including Alzheimer's disease, cause the motor and cognitive malfunctions that are spontaneously stressful and also can disturb the neural circuits that promote stress responses. The interruption of those circuits leads to aggressive and inappropriate behavior. In addition, stress contributes to illness and may exacerbate symptoms. In this review, we present stress-activated neural pathways involved in Alzheimer's disease from a clinical and experimental point of view, as well as supportive drugs and therapies.
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Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Humanos , Qualidade de VidaRESUMO
Mesenchymal stem cells (MSCs) have been recently shown to improve functional recovery in animal models of CNS disorders and are currently being examined in clinical studies for sclerosis, stroke, and CNS lesions. The activation of endogenous CNS protection and repair mechanisms is unclear. MSC-based approaches are considered a new potential target for neurodegenerative disorders. This study was designed to discover the effect of MSCs injection in the nucleus accumbens (NAc) on the reinstatement of behavior in morphine-induced conditioned place preference (CPP) in male rats. The CPP was induced via intra-peritoneal (i.p.) morphine injection (5 mg/kg) for three consecutive days. After being tested for CPP induction, animals received MSCs or culture medium (DMEM F-12) in their NAc using stereotaxic surgery. Following extinction, a priming dose of morphine (2 mg/kg) was administered to induce reinstatement. Expression of GluN1, GluN2A, and GluN2B subunits of the NMDA receptor and the NT-3 gene in the NAc was assessed on the last day of extinction and following CPP reinstatement. The results showed that local injection of MSCs attenuated reinstatement after receiving a priming dose of morphine, and also shortened the period of CPP extinction. The mRNA expression of the NT-3 gene in the group receiving MSCs was increased compared to control animals, as was observed for GluN1 and GluN2B, but not GluN2A. It is concluded that intra-NAc injection of MSCs may facilitate morphine extinction and alleviate reinstatement behavior which may be via expression changes in NMDA receptor subunits and NT-3 gene.
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Morfina , Núcleo Accumbens , Ratos , Masculino , Animais , Morfina/farmacologia , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Extinção Psicológica/fisiologiaRESUMO
Opioid addiction causes some molecular alterations in the brain reward pathway, such as changes in gene expression that may be transferred to the next generation via epigenetic mechanisms such as histone acetylation. This study aimed to evaluate the effect of theophylline as an HDAC (Histone deacetylases) activator on D1 and D2 dopamine receptor expression in the nucleus accumbens (NAc) and anxiety behavior in the offspring of morphine-dependent female rats. Female rats were exposed to escalating doses of morphine for six days and were then treated with theophylline (20 mg/kg) or saline for 10 days before mating with normal male rats. Male and female offspring were tested for anxiety behavior using an elevated plus maze apparatus. Besides, the expression of D1 and D2 dopamine receptors in the NAc was evaluated by real-time PCR (polymerase chain reaction). Results showed that offspring of morphine-dependent female rats had increased expression of both D1 and D2 receptors in the NAc, as well as decreased anxiety behavior, compared to control offspring. However, the mentioned effects were returned to normal levels in the offspring whose morphine-dependent mothers had received theophylline for 10 days before mating. It is concluded that theophylline may be therapeutically effective in minimizing the adverse consequences of maternal morphine dependence on offspring behavior by restoring normal dopamine receptor expression levels and modulating anxiety. To completely comprehend the underlying mechanisms of this phenomenon, more research is required.
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Dependência de Morfina , Ratos , Masculino , Feminino , Animais , Dependência de Morfina/metabolismo , Teofilina/farmacologia , Morfina/efeitos adversos , Ansiedade/prevenção & controle , Ansiedade/etiologia , Transtornos de Ansiedade , Núcleo Accumbens/metabolismo , Receptores de Dopamina D1/metabolismoRESUMO
Introduction: The opiate dosage adequacy scale (ODAS) is one of the most common assessment tools in studies on substance use disorders, which evaluates the "adequacy" of opiate medication doses in individuals recruited in maintenance approaches. There is no investigation on the Persian version of this questionnaire in Iran. This research validated a Persian version of the ODAS. Methods: The Persian version of the ODAS was translated and revised based on the original scale presented by González-Saiz et al. The psychometric characteristics of the ODAS were assessed via direct interviews. Three trained interviewers questioned 250 patients treated in methadone maintenance clinics in Mazandaran Province (Northern Iran) for more than three months. Internal consistency and factor analysis were conducted using SPSS software, version 24. Results: The internal consistency of ODAS was satisfactory (Cronbach's α=0.81). Across all items, considerable inter-rater reliability was discovered (kappa values between 0.90 and 1). A four-component structure was produced by the factor analysis that accounted for 77.5% of the total variance. Cronbach's α coefficients of the four components of Heroin craving and overmedication, Consumption, objective opiate withdrawal symptoms, and subjective opiate withdrawal symptoms were 0.84, 0.91, 0.83, and 0.74, respectively. Conclusion: The reliability and validity of the Persian version of the ODAS were satisfactory in a sample of methadone maintenance subjects. Highlights: The opiate dosage adequacy scale (ODAS) is a clinical tool for measuring the adequacy of methadone dosesThe Persian version of ODAS has good validity, internal consistency, and inter-rater reliability;The Persian version of the ODAS, as a valid and reliable tool, can be used for the Iranian people under methadone maintenance. Plain Language Summary: In Iran, opioids are among the most common forms of illicit drugs. In opioid maintenance programs, the adequacy of methadone doses has an important effect on treatment outcomes. Clinicians typically assess the adequacy of doses based on the patient's response to the medication. Different tools are used in clinical studies to evaluate it. One of these tools is the ODAS, developed by González-Saiz et al. In the present study, we validated the Persian version of the ODAS for Iranian patients receiving methadone maintenance programs. The results confirmed the four-factor structure of the Persian ODAS and showed its good internal consistency and inter-rater reliability.