OBJECTIVETo explore the mechanism of Yizhi Jiannao Granule (YZJN) in treating Alzheimer's disease (AD) on proteomic level by analyzing the differential expression proteins in entorhinal cortex tissue of senescence accelerated mouse P8 (SAMP8) treated with YZJN.

METHODSSix-month old SAMP8 were randomly divided into 3 groups, the model group, the YZJN group and the control group, 10 mice in each group. The model group was untreated with free water access, the YZJN group was treated with concentrated water extract of YZJN 0.3 g per day via gastric perfusion, and the control group was perfused with equal volume of double distilled water. The total protein in entorhinal cortex tissue of mice was extracted after an 8-week treatment with two-dimensional gel electrophoresis, and the differential expression protein spots were separated for identification through peptide mass fingerprint analysis and database searching.

RESULTSThirty-two protein spots expressed differentially between the YZJN group and the model group were found, and 14 differential expression proteins were identified, including NADH dehydrogenase iron-sulfur protein 6, Rho-GDP dissociation inhibitor alpha, beta2-globin, phosphoglyceric kinase, etc, their functions involved mitochondria energy metabolism, oxidative stress and neuron function.

CONCLUSIONYZJN could regulate multiple protein expressions in entorhinal cortex tissues of SAMP8, suggesting that it has multi-target therapeutic action and its mechanism in treating AD is possibly realized by way of improving mitochondria function, antagonizing oxidation stress, preventing nerve cell apoptosis and protecting neurons.

Aging ; metabolism ; Alzheimer Disease ; metabolism ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Entorhinal Cortex ; metabolism ; Male ; Mice ; Neurons ; metabolism ; Oxidative Stress ; Proteins ; metabolism ; Proteome ; analysis ; Proteomics

Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (I_h), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the I_h. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
Animals ; Chronic Pain ; Entorhinal Cortex/metabolism* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Neurons/metabolism* ; Rats ; Receptors, Dopamine D1/metabolism* ; Receptors, Dopamine D2

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal