Novel derivative of Paeonol, Paeononlsilatie sodium, alleviates behavioral damage and hippocampal dendritic injury in Alzheimer's disease concurrent with cofilin1/phosphorylated-cofilin1 and RAC1/CDC42 alterations in rats

Abstract

Alzheimer’s disease (AD) is a typical hippocampal amnesia and the most common senile dementia. Many studies suggest that cognitive impairments are more closely correlated with synaptic loss than the burden of amyloid deposits in AD progression. To date, there is no effective treatment for this disease. Paeonol has been widely employed in traditional Chinese medicine. This compound improves learning behavior in an animal model; however, the mechanism remains unclear. In this study, Paeononlsilatie sodium (Pa), a derivative of Paeonol, attenuated D-galactose (D-gal) and AlCl3-induced behavioral damages in rats based on evaluations of the open field test (OFT), elevated plus maze test (EPMT), and Morris water maze test (MWMT). Pa increased the dendritic complexity and the density of dendritic spines. Correlation analysis indicated that morphological changes in neuronal dendrites are closely correlated with behavioral changes. Pa treatment reduced the production of Aβ, affected the phosphorylation and redistribution of cofilin1 and inhibited rod-like formation in hippocampal neurons. The induction of D-gal and AlCl3 promoted the expression of RAC1/CDC42 expression; however, the tendency of gene expression was inhibited by pretreatment with Pa. Taken together, our results suggest that Pa may represent a novel therapeutic agent for the improvement of cognitive and emotional behaviors and dendritic morphology in an AD animal model.

Possible prophylactic anti-excitotoxic and anti-oxidant effects of virgin coconut oil on aluminium chloride-induced Alzheimer’s in rat models

“…It has been reported that aluminum-mediated cellular injury targets lipids, protein and DNA, which in turn induce oxidative stress, lipid peroxidation and cell injury [11,13,67]. Based on these considerations, in this study AlCl 3 was chosen to induce a model of sporadic AD [2,26,28], with the overall goal of investigating the possible prophylactic effect of VCO in an AlCl 3 -induced AD rat model.…”

Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid β

“…(1) Central crossing, ( 2 ) central time, ( 3 ) peripheral crossing, ( 4 ) peripheral time, and ( 5 ) total crossing ( 25 26 ).…”

“…The maze was elevated from the ground by 50 cm using stands. The duration of the presence of the rats in the open and enclosed arms was recorded using a digital camera for 5 min ( 25 ).…”

Role of Cofilin in Alzheimer’s Disease

“…The Rac1/cofilin pathway is inactivated through suppression of the cofilin phosphorylation which causes the loss of dendritic spine in the hippocampus (Yang et al, 2018). The density of dendritic spines and dendritic complexity increase, similar to the change of phosphorylation and redistribution of cofilin-1 in an AD rat model (Han et al, 2017). Cofilin-1 knockdown leads to a decrease number of thin spines and decrease length of dendritic protrusions (Hotulainen et al, 2009).…”