Lamotrigine protects against cognitive deficits,synapse and nerve cell damage,and hallmark neuropathologies in a mouse model of Alzheimer’s disease

Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.

Effect of Kangxin Capsule (康欣胶囊) on the Expression of Nerve Growth Factors in Parietal Lobe of Cortex and Hippocampus CA_1 Area of Vascular Dementia Model Rats

Objective： To observe the effect of Kangxin Capsule （康欣胶囊, KXC） on the expression of nerve growth factor （NGF） as well as the morphology and amount of nerve synapse in the cortical parietal lobe and hippocampus CA; area of vascular dementia （VD） model rats. Methods： The model rats of VD made by photochemical reaction technique were randomly divided into five groups： the model group （MG）, the high-dose, middle-dose and low-dose KXC groups （HDG, MDG and LDG）, and the Western medicine hydergin control group （WMG）. They were treated respectively with distilled water, high, middle and low dosage of KXC suspended liquid, and hydergin for a month. Besides, a blank group consisting of normal （non-model） rats was set up for control （CG）. The ultrastructure of nerve synapse in the cortical parietal lobe and hippocampus CA~ area of the rats were observed and its density estimated. The condition of NGF positive neurons in the above-mentioned two regions were also observed by immunohistochemical stain. Results： All the KXC or hydergin treated groups demonstrated a normal amount of nerve synapse with integral structure in the cortical parietal lobe and hippocampus OA; area, which approached that in the CG and was superior to that in the MG. Also, the NGF positive neuron in all the treated groups was much more than that in MG with significant difference （ P〈0.01 ）, approaching to that in the CG. Conclusion： KXC could elevate the expression of NGF in the cortical parietal lobe and hippocampus CA; area, preserve the number and morphology of synapse, thus to protect the function of nerve system from ischemic injury.