RESUMO
The potential of Marrubium vulgare to alleviate scopolamine (Sco)-induced deficits in spatial working memory has drawn considerable scientific interest. This effect is partly attributed to its potent antioxidant and acetylcholinesterase inhibitory (AChEI) activities. This study examined the effects of M. vulgare extract, standardized to marrubiin content, on recognition memory in healthy and Sco-treated rats. Male Wistar rats (200-250 g) were divided into four groups. The extract was orally administered for 21 days and Sco (2 mg/kg) was intraperitoneally injected for 11 consecutive days. Memory performance was assessed using the novel object recognition test. Levels of acetylcholine (ACh), noradrenaline (NA), serotonin (Sero), and brain-derived neurotrophic factor (BDNF) and the phosphorylation of cAMP response element-binding protein (p-CREB) were evaluated in the cortex and hippocampus via ELISA. BDNF and CREB expression levels were assessed using RT-PCR. The results showed that M. vulgare significantly alleviated Sco-induced memory impairment, preserved cholinergic function in the hippocampus, increased NA levels in the brain, and restored pCREB expression in the cortex following Sco-induced reduction. In healthy rats, the extract upregulated BDNF, pCREB, and Bcl2 expression. Our findings indicate that the neuroprotective effects of M. vulgare may be linked to the modulation of cholinergic function, regulation of NA neurotransmission, and influence on key memory-related molecules.
RESUMO
BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disease with multifactorial etiology, unsatisfactory treatment, and a necessity for broad-spectrum active substances for cure. The mucus from Helix aspersa snail is a mixture of bioactive molecules with antimicrobial, anti-inflammatory, antioxidant, and anti-apoptotic effects. So far there are no data concerning the capacity of snail extract (SE) to affect neurodegenerative disorders. OBJECTIVE: The effects of SE from Helix aspersa on learning and memory deficits in Alzheimer's type dementia (ATD) induced by scopolamine (Sco) in male Wistar rats were examined and some mechanisms of action underlying these effects were evaluated. METHODS: SE (0.5âmL/100âg) was applied orally through a food tube for 16 consecutive days: 5 days before and 11 days simultaneously with Sco (2âmg/kg, intraperitoneally). At the end of Sco treatment, using behavioral methods, we evaluated memory performance. Additionally, in cortex and hippocampus the acetylcholinesterase (AChE) activity, acetylcholine and monoamines (dopamine, noradrenaline, and serotonin) content, levels of main oxidative stress markers, and expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) were determined. RESULTS: We demonstrated that, according to all behavioral tests used, SE significantly improved the cognitive deficits induced by Sco. Furthermore, SE possessed AChE inhibitory activity, moderate antioxidant properties and the ability to modulate monoamines content in two brain structures. Moreover, multiple SE applications not only restored the depressed by Sco expression of CREB and BDNF, but significantly upregulated it. CONCLUSION: Summarizing results, we conclude that complex mechanisms underlie the beneficial effects of SE on impaired memory in Alzheimer's type dementia.
Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Acetilcolinesterase/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Antioxidantes , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória/metabolismo , Modelos Teóricos , Doenças Neurodegenerativas/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Escopolamina/metabolismoRESUMO
FMR1 gene (fragile X mental retardation 1) represents a genetic and epigenetic factor in a number of human diseases. Though the role of FMR1 gene in substance use disorders (SUDs) is not well studied, a number of investigations indicate that SUDs and FMR1-accociated disorders may share common underlying mechanisms. We examined the relative FMR1 mRNA levels and their sex-distribution in leukocytes from patients with alcohol and drug dependence compared to healthy controls. The study included 44 participants, 16 with alcohol dependence (mean age 43, 10 males and 6 females), 17 with drug dependence (mean age 41, 12 males and 5 females) and 11 healthy controls (mean age 47, 5 males and 6 females). Participants donated 5-6 ml of blood and completed a specialized questionnaire. Total RNA was isolated and cDNA was synthesized and used as a template for qRT-PCR analysis. The studied persons with alcohol and drug dependence share common socio-demographic and substance-use related characteristics. Significant FMR1 down-regulation was observed in the alcohol dependent group (25 % decrease; p = 0.005). Sex-associated analysis revealed that FMR1 down-regulation was primarily in alcohol-dependent men (40% decrease; p = 0.001) and did not reach significance in women. A similar sex-dependent pattern was observed among drug-dependent individuals. Drug-dependent men had significantly lower FMR1 mRNA levels (24% decrease; p = 0.015) compared with controls, while no significant difference was observed in drug-dependent females. These data indicate FMR1 mRNA down-regulation in persons with alcohol- and drug-dependence, relative to controls, is sex-dependent. This implies a role for FMR1 in substance use disorders. These findings require confirmation by including protein measures and the recruitment of larger cohorts.