title: Intra-amygdala microinjection of TNF-α impairs the auditory fear conditioning of rats via glutamate toxicity.
abstract: During an inflammatory or infectious process, innate immune cells produce large amount of pro-inflammatory cytokines that act on the brain to cause cognitive dysfunctions. Tumor necrosis factor alpha (TNF-α) is one of the main pro-inflammatory cytokines. Thus, it is important to study how the excessive TNF-α affects the cognitive functions of central nervous system and possible antagonists to its effects. In the present study, we conducted behavioral experiments of rats to determine whether murine TNF-α administered directly into the brain would elicit behavioral effects related to learning and memory impairments. Rats subjected to single-dose intra-amygdala TNF-α infusion showed a significant delay in the acquisition and extinction of auditory fear conditioning. Accordingly, the glutamate level of the tissue samples from amygdala was elevated after the TNF-α treatment. Furthermore, pharmacological blockade of NMDAR before the TNF-α treatment reversed the TNF-α induced impairments in fear learning. Our findings suggest that TNF-α can impair the learning and memory functions through glutamate-NMDAR neurotoxicity, and present the possibility to develop therapeutic modalities directing at glutamate transmission for the treatment of neuro-inflammative dysfunctions.
authors.affiliation: Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China. Electronic address: 254606003@qq.com.
authors.forename: He
authors.initials: H
authors.lastname: Jing
authors.affiliation: Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China. Electronic address: haoyongxin0428@126.com.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China. Electronic address: 79027747@qq.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Jiaozhen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China. Electronic address: yangpingtingting@163.com.
authors.forename: Pingting
authors.initials: P
authors.lastname: Yang
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D005239:Fear; D018698:Glutamic Acid / Q000378:metabolism*; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008845:Microinjections; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Amygdala; Fear conditioning; Glutamate; NMDAR; TNF-α