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Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer's Disease Through Activation of BDNF-TrkB Signaling Pathway.

ABSTRACT: Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by impairments of cognitive function as a result of synaptic deficits and neuronal loss, is associated with inflammation. Apelin-13, a predominant neuropeptide with inhibiting effect on inflammation, has beneficial effects on cognition memory and neuronal damage. However, whether apelin-13 can protect neurons to ameliorate cognitive deficits in AD by inhibiting the inflammatory response remains largely unknown. To test this hypothesis, rats were intracerebroventricularly (ICV) injected with streptozotocin (3 mg/kg) alone or in combination with apelin-13 (2 ?g). And tyrosine receptor kinase B (TrkB) blocker K252a (200 nM) was administrated 10 min before apelin injection. Furthermore, cognitive performance was assessed by new object recognition (NOR) and Y-maze tests. Protein expression of apelin, APJ, microglial marker (IBA1), astroglia marker (GFAP), interleukin 1 beta (IL-1?), tumor necrosis factor-? (TNF-?), synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB) in the hippocampus were examined by western blotting or immunohistochemistry. And the gene expression of IBA1, GFAP, IL-1?, TNF-?, and SYP were detected by real-time quantitative polymerase chain reaction (PCR). Inflammatory disorder in the hippocampus was tested by hematoxylin and eosin (H&E) staining. The enzyme-linked immunosorbent assay (ELISA) was used to study the expression level of acetylcholine. And the activity of acetylcholinesterase was detected by Acetylcholinesterase Assay Kit. We observed that apelin/APJ signaling was downregulated in the hippocampus of rats administrated with STZ. Apelin-13 was found to significantly ameliorate STZ-induced AD-like phenotypes including congnitive deficit, cholinergic disfunction and the damage of neuron and synaptic plasticity. Moreover, apelin-13 inhibited microglia and astrocyte activation, reduced IL-1? and TNF-? expression and hippocampal BDNF/TrkB expression deficit in AD rats. Finally, apelin-13-mediated effects were blocked by TrkB receptor antagonist K252a. These results suggest that apelin-13 upregulates BDNF/TrkB pathway against cognitive deficit in a STZ-induced rat model of sporadic AD by attenuating inflammation.

SUBMITTER: Luo H

PROVIDER: S-EPMC6477031 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer's Disease Through Activation of BDNF-TrkB Signaling Pathway.

Luo Huaiqing H Xiang Yang Y Qu Xiangping X Liu Huijun H Liu Chi C Li Guangyi G Han Li L Qin Xiaoqun X

Frontiers in pharmacology 20190416

Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by impairments of cognitive function as a result of synaptic deficits and neuronal loss, is associated with inflammation. Apelin-13, a predominant neuropeptide with inhibiting effect on inflammation, has beneficial effects on cognition memory and neuronal damage. However, whether apelin-13 can protect neurons to ameliorate cognitive deficits in AD by inhibiting the inflammatory response remains largely unknown. To te ...[more]

PMID: 31040784

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Project description:BACKGROUND: In rodents, dietary Na+ deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na+ stimulation. However, in the rat taste bud cells Na+ deprivation increases the number of amiloride sensitive epithelial Na+ channels (ENaC), which are considered as the "receptor" of the Na+ component of salt taste. To explore the mechanisms, the expression of the three ENaC subunits (alpha, beta and gamma) in taste buds were observed from rats fed with diets containing either 0.03% (Na+ deprivation) or 1% (control) NaCl for 15 days, by using in situ hybridization and real-time quantitative RT-PCR (qRT-PCR). Since BDNF/TrkB signaling is involved in the neural innervation of taste buds, the effects of Na+ deprivation on BDNF and its receptor TrkB expression in the rat taste buds were also examined. RESULTS: In situ hybridization analysis showed that all three ENaC subunit mRNAs were found in the rat fungiform taste buds and lingual epithelia, but in the vallate and foliate taste buds, only alpha ENaC mRNA was easily detected, while beta and gamma ENaC mRNAs were much less than those in the fungiform taste buds. Between control and low Na+ fed animals, the numbers of taste bud cells expressing alpha, beta and gamma ENaC subunits were not significantly different in the fungiform, vallate and foliate taste buds, respectively. Similarly, qRT-PCR also indicated that Na+ deprivation had no effect on any ENaC subunit expression in the three types of taste buds. However, Na+ deprivation reduced BDNF mRNA expression by 50% in the fungiform taste buds, but not in the vallate and foliate taste buds. The expression of TrkB was not different between control and Na+ deprived rats, irrespective of the taste papillae type. CONCLUSION: The findings demonstrate that dietary Na+ deprivation does not change ENaC mRNA expression in rat taste buds, but reduces BDNF mRNA expression in the fungiform taste buds. Given the roles of BDNF in survival of cells and target innervation, our results suggest that dietary Na+ deprivation might lead to a loss of gustatory innervation in the mouse fungiform taste buds.

Dataset Information

Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer's Disease Through Activation of BDNF-TrkB Signaling Pathway.

Publications

Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer's Disease Through Activation of BDNF-TrkB Signaling Pathway.

Similar Datasets

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