Effects of Huperzin-A on the Beta-amyloid accumulation in the brain and skeletal muscle cells of a rat model for Alzheimer's disease.

Aims: Alzheimer's Disease (AD) is characterized by a loss of cognitive function and also the accumulation of β-amyloid peptide (βAP) in the brain parenchyma, which plays an important role in this disease. However, it is often also associated with the non-cognitive symptoms such as loss of muscle function (Inclusion-Body Myositis-IBM).

Main Methods: Sprague-Dawley rats (13 weeks-n=68) were randomly assigned into five groups: Group C: Control; Group D: d-galactose; Group O+D: Bilateral oophorectomy+d-galactose; Group O: Bilateral oophorectomy; Group O+D+H: Bilateral oophorectomy+d-galactose+Hup-A. Tissue fixation was performed with the perfusion method. The Compound Muscle Action Potential (CMAP) and mechanical muscle activity were recorded using the standard electro-biophysical techniques. Immune staining was performed with specific antibodies, and the pathological changes were examined. RNA was obtained from brain tissue samples with the Trizol Method. Then, the expression data of mature-miRNAs (rno-miR-9-5p, rno-miR-29a-3p, rno-miR-106a-5p, rno-miR-107 and rno-miR-125a-3p), which may be effective in AD, were taken with Real-Time PCR.

Key Findings: Impairments occurred in behavioral tests of the rats in the O+D group. βAP accumulation and AChE activity increased significantly in the forebrain in the O+D group compared to the C group. It was seen that Huperzine-A (Hup-A) reduced AChE activity and destructed βAP accumulation. There was a significant decrease in the maximum contractile force at different frequencies in the O+D group and in the O group compared to the C group.

Significance: It was found that Hup-A contributed to the healing process in rats for damage occurring both in the brain and in the neuro-muscular system.