Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice
Neonatal inflammation can increase the risk of anxiety disorder in adulthood. The balance between glutamatergic excitatory and GABAergic inhibitory transmissions in the basolateral amygdala (BLA) plays a vital role in controlling anxiety state. Based on the reports that early-life inflammation had a...
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Elsevier
2022-07-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122001371 |
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| author | Haiquan Zhong Jing Rong Yang Yang Min Liang Yingchun Li Rong Zhou |
| author_facet | Haiquan Zhong Jing Rong Yang Yang Min Liang Yingchun Li Rong Zhou |
| author_sort | Haiquan Zhong |
| collection | DOAJ |
| description | Neonatal inflammation can increase the risk of anxiety disorder in adulthood. The balance between glutamatergic excitatory and GABAergic inhibitory transmissions in the basolateral amygdala (BLA) plays a vital role in controlling anxiety state. Based on the reports that early-life inflammation had adverse effects on GABAergic system, the aim of this study was to investigate whether and how neonatal inflammation affects excitatory-inhibitory circuits in the BLA resulting in anxiety disorder. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 μg/kg) or saline on postnatal days 3–5. LPS-treated mice developed anxiety behaviors accompanied by the hyperactivity of adrenal axis in adulthood. Electrophysiological study revealed the increase of postsynaptic neuronal excitability in the cortical-BLA excitatory synapses of LPS mice which could be recovered by bath-application of GABAAR agonist suggesting the impairment of GABAergic system in LPS mice. Compared with controls, GABAARα2 subunit expression and density of GABA-evoked current in BLA principal neurons were reduced in LPS mice. Additionally, neonatal LPS treatment resulted in the down-regulation of transforming growth factor-beta 1 (TGF-β1) expression and PKC signaling pathway in the adult BLA. The local TGF-β1 overexpression in the BLA improved GABAARα2 expression via up-regulating the activity of PKC signaling, which corrected GABAAR-mediated inhibition leading to the abolishment of anxiety-like change in adrenal axis regulation and behaviors in LPS mice. These data suggest the persistent TGF-β1deficit induces the down-regulation of GABAARα2 expression and subsequent disruption of the excitation-inhibition balance in the BLA circuits, which is the important mechanisms of neonatal inflammation-induced anxiety disorder. |
| first_indexed | 2024-12-12T04:21:21Z |
| format | Article |
| id | doaj.art-77175e1cc2064318be697e2d122742fb |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-12T04:21:21Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
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| series | Neurobiology of Disease |
| spelling | doaj.art-77175e1cc2064318be697e2d122742fb2022-12-22T00:38:19ZengElsevierNeurobiology of Disease1095-953X2022-07-01169105745Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult miceHaiquan Zhong0Jing Rong1Yang Yang2Min Liang3Yingchun Li4Rong Zhou5Department of Physiology, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Physiology, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Physiology, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Physiology, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Physiology, Nanjing Medical University, Nanjing 211166, ChinaCorresponding author at: Department of Physiology, Nanjing Medical University, Longmian Avenue 101, Jiangning District, Nanjing City 211166, Jiangsu Province, China.; Department of Physiology, Nanjing Medical University, Nanjing 211166, ChinaNeonatal inflammation can increase the risk of anxiety disorder in adulthood. The balance between glutamatergic excitatory and GABAergic inhibitory transmissions in the basolateral amygdala (BLA) plays a vital role in controlling anxiety state. Based on the reports that early-life inflammation had adverse effects on GABAergic system, the aim of this study was to investigate whether and how neonatal inflammation affects excitatory-inhibitory circuits in the BLA resulting in anxiety disorder. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 μg/kg) or saline on postnatal days 3–5. LPS-treated mice developed anxiety behaviors accompanied by the hyperactivity of adrenal axis in adulthood. Electrophysiological study revealed the increase of postsynaptic neuronal excitability in the cortical-BLA excitatory synapses of LPS mice which could be recovered by bath-application of GABAAR agonist suggesting the impairment of GABAergic system in LPS mice. Compared with controls, GABAARα2 subunit expression and density of GABA-evoked current in BLA principal neurons were reduced in LPS mice. Additionally, neonatal LPS treatment resulted in the down-regulation of transforming growth factor-beta 1 (TGF-β1) expression and PKC signaling pathway in the adult BLA. The local TGF-β1 overexpression in the BLA improved GABAARα2 expression via up-regulating the activity of PKC signaling, which corrected GABAAR-mediated inhibition leading to the abolishment of anxiety-like change in adrenal axis regulation and behaviors in LPS mice. These data suggest the persistent TGF-β1deficit induces the down-regulation of GABAARα2 expression and subsequent disruption of the excitation-inhibition balance in the BLA circuits, which is the important mechanisms of neonatal inflammation-induced anxiety disorder.http://www.sciencedirect.com/science/article/pii/S0969996122001371LipopolysaccharideDevelopmental neurological disorderBasolateral amygdalaGABAergic systemCytokines |
| spellingShingle | Haiquan Zhong Jing Rong Yang Yang Min Liang Yingchun Li Rong Zhou Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice Neurobiology of Disease Lipopolysaccharide Developmental neurological disorder Basolateral amygdala GABAergic system Cytokines |
| title | Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice |
| title_full | Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice |
| title_fullStr | Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice |
| title_full_unstemmed | Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice |
| title_short | Neonatal inflammation via persistent TGF-β1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice |
| title_sort | neonatal inflammation via persistent tgf β1 downregulation decreases gabaar expression in basolateral amygdala leading to the imbalance of the local excitation inhibition circuits and anxiety like phenotype in adult mice |
| topic | Lipopolysaccharide Developmental neurological disorder Basolateral amygdala GABAergic system Cytokines |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122001371 |
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