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Role of monocarboxylate transporter 4 in Alzheimer disease.
Neurotoxicology 2019; 76:191-199N

Abstract

The pathological process of Alzheimer disease (AD) is closely related to energy metabolism disorders. In the nervous system, monocarboxylate transporter 4 (MCT4) is expressed in the glial cell membrane and is responsible for transporting intracellular lactic acid. In this study, we found that MCT4 expression was elevated in the cerebrospinal fluid of patients with mild cognitive impairment. Two- and three-month-old APPswe/PS1dE9 (APP/PS1) mice and C57 mice were studied. The APP/PS1 mice began to show cognitive decline at 3 months of age and MCT4 in the hippocampus of 2- and 3-month old APP/PS1 mice was higher than that of C57 mice. This change is similar to that in people with mild cognitive impairment. Subsequently, MCT4 overexpression/siRNA lentiviral particles were used to establish stable primary astrocytes. Overexpression and knockdown of MCT4 had no significant effect on glial cell apoptosis. Transfected astrocytes were co-cultured with neurons. Overexpression of cytoplasmic MCT4 increased the expression of Aβ42, γ-secretase, and CD147 in the co-culture system; in addition, the growth ability of primary neurons decreased significantly, extracellular lactic acid increased, and neuronal apoptosis increased. In AD model mice, siMCT4 injection improved cognitive ability, reduced neuronal apoptosis, and reduced γ-secretase expression. Taken together, these results suggest that MCT4 is involved in energy metabolism during early pathological processes in AD, and suppression of MCT4 represents a new potential neuroprotective factor for AD.

Authors+Show Affiliations

Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.Department of Administration Management, Weifang People's Hospital, Weifang, Shandong Province, 261000, China.Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. Electronic address: neurologists@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31738978

Citation

Hong, Ping, et al. "Role of Monocarboxylate Transporter 4 in Alzheimer Disease." Neurotoxicology, vol. 76, 2019, pp. 191-199.
Hong P, Zhang X, Gao S, et al. Role of monocarboxylate transporter 4 in Alzheimer disease. Neurotoxicology. 2019;76:191-199.
Hong, P., Zhang, X., Gao, S., & Wang, P. (2019). Role of monocarboxylate transporter 4 in Alzheimer disease. Neurotoxicology, 76, pp. 191-199. doi:10.1016/j.neuro.2019.11.006.
Hong P, et al. Role of Monocarboxylate Transporter 4 in Alzheimer Disease. Neurotoxicology. 2019 Nov 16;76:191-199. PubMed PMID: 31738978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of monocarboxylate transporter 4 in Alzheimer disease. AU - Hong,Ping, AU - Zhang,Xiaoyi, AU - Gao,Shichao, AU - Wang,Peichang, Y1 - 2019/11/16/ PY - 2019/06/10/received PY - 2019/11/09/revised PY - 2019/11/11/accepted PY - 2019/11/19/pubmed PY - 2019/11/19/medline PY - 2019/11/19/entrez KW - Alzheimer disease KW - Apoptosis KW - Lactic acid KW - Mitochondria KW - Monocarboxylate transporter 4 SP - 191 EP - 199 JF - Neurotoxicology JO - Neurotoxicology VL - 76 N2 - The pathological process of Alzheimer disease (AD) is closely related to energy metabolism disorders. In the nervous system, monocarboxylate transporter 4 (MCT4) is expressed in the glial cell membrane and is responsible for transporting intracellular lactic acid. In this study, we found that MCT4 expression was elevated in the cerebrospinal fluid of patients with mild cognitive impairment. Two- and three-month-old APPswe/PS1dE9 (APP/PS1) mice and C57 mice were studied. The APP/PS1 mice began to show cognitive decline at 3 months of age and MCT4 in the hippocampus of 2- and 3-month old APP/PS1 mice was higher than that of C57 mice. This change is similar to that in people with mild cognitive impairment. Subsequently, MCT4 overexpression/siRNA lentiviral particles were used to establish stable primary astrocytes. Overexpression and knockdown of MCT4 had no significant effect on glial cell apoptosis. Transfected astrocytes were co-cultured with neurons. Overexpression of cytoplasmic MCT4 increased the expression of Aβ42, γ-secretase, and CD147 in the co-culture system; in addition, the growth ability of primary neurons decreased significantly, extracellular lactic acid increased, and neuronal apoptosis increased. In AD model mice, siMCT4 injection improved cognitive ability, reduced neuronal apoptosis, and reduced γ-secretase expression. Taken together, these results suggest that MCT4 is involved in energy metabolism during early pathological processes in AD, and suppression of MCT4 represents a new potential neuroprotective factor for AD. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/31738978/Role_of_monocarboxylate_transporter_4_in_Alzheimer_disease L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(19)30133-0 DB - PRIME DP - Unbound Medicine ER -