RESUMO
BACKGROUND AND PURPOSE: Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are involved in the response to stress. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviours. EXPERIMENTAL APPROACH: To model chronic stress, rats were exposed to corticosterone treatment via drinking water for 21 days, and GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for the last 7 days of corticosterone treatment. Behavioural tests were run on days 22 and 23. Depressive- and anxiety-like behaviours were evaluated in forced swim test, sucrose preference test, novelty-suppressed feeding test and social interaction test. The expression of GRs, MRs and CRF were detected by western blot. KEY RESULTS: Rats exposed to corticosterone exhibited depressive- and anxiety-like behaviours. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. The intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behaviours. The spironolactone-treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN and improved anxiety-like behaviours. Interestingly, the intra-PVN administration of RU486 and spironolactone combined restored expression of GRs, MRs and CRF and improved depressive- and anxiety-like behaviours. CONCLUSION AND IMPLICATIONS: In this rat model of stress, the simultaneous restoration of GRs, MRs and CRF in the PVN might play an important role in the treatment of depression and anxiety.
Assuntos
Núcleo Hipotalâmico Paraventricular , Receptores de Mineralocorticoides , Animais , Corticosterona , Hormônio Liberador da Corticotropina/metabolismo , Glucocorticoides/farmacologia , Hipotálamo/metabolismo , Ratos , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum, Lingzhi), also known as "immortality mushroom" has been broadly used to improve health and longevity for thousands of years in Asia. G. lucidum and its spores have been used to promote health, based on its broad pharmacological and therapeutic activity. This species is recorded in Chinese traditional formula as a nootropic and has been suggested to improve cognitive dysfunction in Alzheimer's disease. However, little is known about the nootropic effects and molecular mechanism of action of G. lucidum spores. AIM OF THE STUDY: The present study investigated the protective effects of sporoderm-deficient Ganoderma lucidum spores (RGLS) against learning and memory impairments and its mechanism of action. MATERIALS AND METHODS: In the Morris water maze, the effects of RGLS on learning and memory impairments were evaluated in a rat model of sporadic Alzheimer's disease that was induced by an intracerebroventricular injection of streptozotocin (STZ). Changes in amyloid ß (Aß) expression, Tau expression and phosphorylation, brain-derived neurotrophic factor (BDNF), and the BDNF receptor tropomyosin-related kinase B (TrkB) in the hippocampus were evaluated by Western blot. RESULTS: Treatment with RGLS (360 and 720 mg/kg) significantly enhanced memory in the rat model of STZ-induced sporadic Alzheimer's disease and reversed the STZ-induced increases in Aß expression and Tau protein expression and phosphorylation at Ser199, Ser202, and Ser396. The STZ-induced decreases in neurotrophic factors, including BDNF, TrkB and TrkB phosphorylation at Tyr816, were reversed by treatment with RGLS. CONCLUSION: These findings indicate that RGLS prevented learning and memory impairments in the present rat model of STZ-induced sporadic Alzheimer's disease, and these effects depended on a decrease in Aß expression and Tau hyperphosphorylation and the modulation of BDNF-TrkB signaling in the hippocampus.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Transtornos da Memória/prevenção & controle , Reishi/química , Esporos Fúngicos/química , Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Fosforilação/efeitos dos fármacos , Placa Amiloide/induzido quimicamente , Placa Amiloide/prevenção & controle , Ratos Sprague-Dawley , Receptor trkB/efeitos dos fármacos , Receptor trkB/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/toxicidade , Proteínas tau/efeitos dos fármacos , Proteínas tau/metabolismoRESUMO
OBJECTIVE: To observe the effect of acupuncture in treating diabetic peripheral neuropathy (DPN). METHODS: Sixty patients with DPN were randomly assigned to the acupuncture treated group and the control group, 30 in each group. Besides basic treatment, patients were treated additionally with acupuncture and orally administration of Methycbal (Mecolbalamin) for 8 weeks respectively. Changes of symptoms, blood glucose, HbA1c, whole blood and plasma viscosity, the nerve conduction velocity (NCV) of sensory and motor nerves before and after treatment were observed. RESULTS: Acupuncture can ameliorate symptoms and signs of the nervous system, decrease whole blood and plasma viscosity, and improve the NCV of sensory and motor nerves in patients with DPN. CONCLUSION: The effect of acupuncture in treating DPN is definite.