Repetitive Transcranial Magnetic Stimulation Improves Brain-Derived Neurotrophic Factor and Cholinergic Signaling in the 3xTgAD Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a debilitating disorder involving the loss of plasticity and cholinergic neurons in the cortex. Pharmaceutical treatments are limited in their efficacy, but brain stimulation is emerging as a treatment for diseases of cognition. More research is needed to determine the biochemical mechanisms and treatment efficacy of this technique. OBJECTIVE: We aimed to determine if forebrain repetitive transcranial magnetic stimulation can improve cortical BDNF gene expression and cholinergic signaling in the 3xTgAD mouse model of AD. METHODS: Both B6 wild type mice and 3xTgAD mice aged 12 months were given daily treatment sessions for 14 days or twice weekly for 6 weeks. Following treatment, brain tissue was extracted for immunological stains for plaque load, as well as biochemical analysis for BDNF gene expression and cholinergic signaling via acetylcholinesterase and choline acetyltransferase ELISA assays. RESULTS: For the 3xTgAD mice, both 14 days and 6 weeks treatment regimens resulted in an increase in BDNF gene expression relative to sham treatment, with a larger increase in the 6-week group. Acetylcholinesterase activity also increased for both treatments in 3xTgAD mice. The B6 mice only had an increase in BDNF gene expression for the 6-week group. CONCLUSION: Brain stimulation is a possible non-invasive and nonpharmaceutical treatment option for AD as it improves both plasticity markers and cholinergic signaling in an AD mouse model.

Simultaneous Estimation of Aloe Emodin and Emodin from Rheum emodi, Cassia alata and Aloes by HPTLC.

A simple, precise, specific, accurate high performance thin layer chromatography method was developed for simultaneous estimation of aloe emodin and emodin from medicinal plants like Rheum emodi (Rhubarb), Barbados aloes (dried juice of Aloe barbadensis leaf) and Cassia alata (Candle bush). Thin layer chromatographic aluminum plates pre-coated with silica gel 60 F254 was used as the stationary phase for chromatographic separation of the drugs. Toluene:ethyl acetate:formic acid (10:2:1 v/v/v) was selected as mobile phase and analysis was carried out in absorbance mode at iso-absorptive wavelength of 263 nm. This method shows good resolution for both drugs with retention factor 0.37±0.03 and 0.55±0.03 for aloe emodin and emodin, respectively. The regression analysis data indicated good linear relationship for the calibration plots for aloe emodin and emodin in the range of 300 - 800 ng/spot and 150 - 400 ng/spot and regression coefficient was 0.9993 and 0.9994, respectively. Validation of the method was performed according to International Conference on Harmonisation guidelines for following parameters: Accuracy, precision, limit of detection, linearity, limit of quantification, robustness and specificity. In conclusion, the developed method was found to be rapid, simple, reliable and specific for the identification and quantitation of these anthraquinones in medicinal plants and marketed formulations.

Forced Degradation Studies of Aloe Emodin and Emodin by HPTLC.

Anthraquinones are natural phenolic compounds, which are reported to act as anti-aging, anti-inflammatory, antioxidant, anti-cancer, laxative and antitumor agents. They are abudant in plants like candle bush, aloes, cascara bark and rhubarb. The present work was to observe the effect of different forced degradation conditions by high-performance thin layer chromatography on potential markers i.e. aloe emodin and emodin. Both aloe emodin and emodin were subjected to various forced degradation studies such as oxidation, acid and alkaline hydrolysis, photolysis, hydrolytic and thermal degradation. Aloe emodin, was more susceptible to acid hydrolysis and degradation was found to a lesser extent under thermal degradation whereas significant degradation was observed under acid hydrolysis, lesser extent was observed under alkali hydrolysis for emodin. Forced degradation studies on aloe emodin and emodin gives information about its storage and intrinsic stability conditions considering the advanced pharmaceutical aspects of formulation.