ABSTRACT
Anxiety disorders are one of the most common mental disorders in adults, the cause of which derives from a combination of genetics and environmental factors. A series of animal models have been established according to their pathogenesis to measure the level of anxiety or induce anxiety only, and these models have been widely applied in the non-clinical evaluation of anxiolytics. In this review, we present the current trends in the study of anxiety disorders and summarize typical non-clinical anxiety animal models, including models that both measure anxiety levels and induce anxiety, and models that induce anxiety only. This review summarizes the important issues in standardized non-clinical research of anxiety disorders and proposes criteria for the selection of an appropriate R&D model.
ABSTRACT
Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia among elderly people. The pathogenesis of AD is still unclear, and currently approved drugs only provide symptomatic benefits and do not prevent or delay progressive neurodegeneration. Meanwhile, potential drugs in development are facing great challenges in clinical translation. Therefore, finding effective treatment for the unmet clinical needs of AD is of great economic value and social significance. In this review, we will summarize the current models and pharmacodynamics evaluation methods of anti-AD drug based on the recent studies at home and abroad, and provide reference for drug development in AD at nonclinical stage.
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is among the most common type of motor neuron diseases, and its pathogenesis remains unclear. In recent years, our understanding of the genetic basis of ALS has led to the development of various ALS disease models, which allow for screening of ALS-related drugs and treatment methods. This review focuses on the research progress of ALS, summarizes the systems of commonly used experimental animal models, including transgenic animals, gene knockout approaches and autonomous animal models, points to the problems needing attention in standardized ALS non-clinical research, and proposes the criteria for selection of standardized R&D model.
ABSTRACT
<p><b>BACKGROUND</b>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the fatal disease. Previous studies reported potent efficacy of dl-3-n-butylphthalide (DL-NBP) for several neurodegenerative disorders and cerebral ischemia. SOD1-G93A mice are a mouse model of ALS. In this study, we investigated the efficacy of DL-NBP on this ALS mouse model.</p><p><b>METHODS</b>Sixty SOD1-G93A female mice were divided into four groups. The vehicle control group received 0 mg×kg(-1)×d(-1) DL-NBP. The experimental groups received DL-NBP with doses of 30, 60 or 120 mg×kg(-1)×d(-1), respectively. For measurement of motor activity, the hanging wire test and rotarod test were performed. Survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice per week. The statistical motor unit number estimation (MUNE) technique was used to estimate the number of functioning motor units in gastrocnemius muscle. Muscle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantitation was performed by Nissl staining and microglia activation was observed by immunohistochemistry.</p><p><b>RESULTS</b>Oral administration of 60 mg×kg(-1)×d(-1)1 DL-NBP significantly prolonged survival ((164.78 ± 16.67) days) of SOD1-G93A mice compared with vehicle control ((140.00 ± 16.89) days). Treating mice with DL-NBP (60 mg×kg(-1)×d(-1)) significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that treating SOD1-G93A mice with DL-NBP (60 mg×kg(-1)×d(-1)) slowed the rate of MUNE reduction (P < 0.01). Motor neurons were remarkably preserved in the anterior horns in mice treated with DL-NBP (60 mg×kg(-1)×d(-1)) at the stage of 19 weeks (P < 0.01). Treating mice with DL-NBP (60 mg×kg(-1)×d(-1)) significantly reduced CD11b immunoreactivity compared with vehicle control mice (P < 0.05). No significant effect was observed in mice treated with DL-NBP of 30 or 120 mg×kg(-1)×d(-1).</p><p><b>CONCLUSIONS</b>The post-disease-onset administration of DL-NBP significantly prolonged survival and improved motor performance in SOD1-G93A mice. DL-NBP may be a potential therapeutic agent for ALS.</p>