Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone

Author:

Huang Hui,Zhang Zhongyuan,Xing Mengdan,Jin Zihan,Hu Yue,Zhou Minyu,Wei Hang,Liang Yiwen,Lv Zhiyue

Abstract

Abstract Background Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. Methods We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT–qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice’s energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. Results Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. Conclusions Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection. Graphical Abstract

Funder

National Natural Science Foundation of China

Open project of Key Laboratory of Tropical Disease Prevention and Control of National Health Commission of Hainan Medical College

National Key Research and Development Program of China

Science and Technology Planning Project of Guangdong Province of China

Major Science and Technology Program of Hainan Province

Academician Innovation Platform Special Project of Hainan Province

Key Research and Development Program of Hainan Province

National Parasitic Resources Center of China

Publisher

Springer Science and Business Media LLC

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