Infliximab ameliorates AD-associated object recognition memory impairment.
Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of Aβ oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of Aβ oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-α, visual recognition memory impaired by pre-administered Aβ oligomers dramatically improved and the detrimental Aβ effect on mAChR-LTD was annulled. Taken together, these findings suggest that Aβ-induced inflammation is mediated through TNF-α signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits.
Department of Medicinal Biotechnology, College of Health Sciences and Institute of Convergence Bio-Health, Dong-A University, Busan, 49315, Republic of Korea.
Dong Hyun
DH
Kim
Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea; Department of Neurology, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
Seong-Min
SM
Choi
Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea; Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
Jihoon
J
Jho
Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea; Department of Neurology, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
Man-Seok
MS
Park
Department of Medicinal Biotechnology, College of Health Sciences and Institute of Convergence Bio-Health, Dong-A University, Busan, 49315, Republic of Korea.
Jisu
J
Kang
Departments of Life and Nanopharmaceutical Sciences and of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
Se Jin
SJ
Park
Departments of Life and Nanopharmaceutical Sciences and of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
Jong Hoon
JH
Ryu
Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea; Department of Neurology, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea; Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea. Electronic address: jihoon.jo@jnu.ac.kr.
Jihoon
J
Jo
DNA Damage Response Center, Chosun University School of Medicine, Gwangju, 61452, Republic of Korea.
Hyun Hee
HH
Kim
Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea; Department of Neurology, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea; Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea. Electronic address: byeong.kim7@gmail.com.
Byeong C
BC
Kim
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D000069285:Infliximab / Q000494:pharmacology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008813:Mice, Inbred ICR; D018697:Nootropic Agents / Q000494:pharmacology*; D010364:Pattern Recognition, Visual / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D000071039:Perirhinal Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011976:Receptors, Muscarinic / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018697:Nootropic Agents; D010446:Peptide Fragments; D011976:Receptors, Muscarinic; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D000069285:Infliximab
Alzheimer’s disease; Infliximab; Muscarinic acetylcholine receptor-dependent long-term depression; Visual recognition memory