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LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice
- Source :
- Alzheimer's Research & Therapy
- Publisher :
- Springer Nature
-
Abstract
- Background Accumulating evidence implicates the neuroendocrine immunomodulation (NIM) network in the physiopathological mechanism of Alzheimer’s disease (AD). Notably, we previously revealed that the NIM network is dysregulated in the PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD. Methods After treatment with a novel Liuwei Dihuang formula (LW-AFC), mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β (Aβ) deposition, and Aβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an enzyme-linked immunosorbent assay (ELISA) were used to measure cytokine and hormone levels. Lymphocyte subsets were detected using flow cytometry. Data between two groups were compared using a Student’s t test. Comparison of the data from multiple groups against one group was performed using a one-way analysis of variance (ANOVA) followed by a Dunnett’s post hoc test or a two-way repeated-measures analysis of variance with a Tukey multiple comparisons test. Results LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice, including the impairment of object recognition memory, spatial learning and memory, and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed Aβ deposition in the brain, and reduced the concentration of Aβ1–42 in the hippocampus and plasma of APP/PS1 mice. LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone in the pituitary. Moreover, LW-AFC increased CD8+CD28+ T cells, and reduced CD4+CD25+Foxp3+ T cells in the spleen lymphocytes, downregulated interleukin (IL)-1β, IL-2, IL-6, IL-23, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor-α and -β, and upregulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice. Conclusions LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic mice via the restoration of the NIM network to a greater extent than either memantine or donepezil, which supports the use of LW-AFC as a potential agent for AD therapy.
- Subjects :
- Male
0301 basic medicine
Genetically modified mouse
medicine.medical_treatment
Cognitive Neuroscience
Clinical Neurology
PrP-hAβPPswe/PS1ΔE9 transgenic mouse
Hippocampus
Mice, Transgenic
Neuron loss
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Alzheimer Disease
Animals
Learning
Medicine
cognitive behavior
Amyloid-β
Lymphocytes
Cytokine
Pathological
LW-AFC
Hypothalamic Hormones
Behavior, Animal
business.industry
Research
Brain
medicine.disease
Disease Models, Animal
Neuroendocrine
Lymphocyte subset
030104 developmental biology
Neurology
Immunology
Cancer research
Cytokines
Neurology (clinical)
Alzheimer's disease
business
Liuwei Dihuang Decoction
Alzheimer’s disease
030217 neurology & neurosurgery
Drugs, Chinese Herbal
Subjects
Details
- Language :
- English
- ISSN :
- 17589193
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Alzheimer's Research & Therapy
- Accession number :
- edsair.doi.dedup.....add0bcde20fddd3e32a8a65db4fe19e1
- Full Text :
- https://doi.org/10.1186/s13195-016-0226-6