神经损伤与功能重建2019，Vol.14Issue(11)：595,1.DOI:10.16780/j.cnki.sjssgncj.2019.11.020
青少年应激引起腹侧海马长时程增强的持续增加:星形细胞谷氨酰胺合成酶的作用
Persistent increase in ventral hippocampal long-term potentiation by juvenile stress: A role for astrocytic glutamine synthetase*
Ivens S 1Çalışkan 2Papageorgiou I 3Cesetti T 4Malich A 5Kann O 6Heinemann U 7Stork O 6Albrecht A8
作者信息
- 1. Department of Psychiatry and Psychotherapy, Charité--Universitätsmedizin Berlin, Berlin, Germany
- 2. Institute for Neurophysiology, -Universitätsmedizin Berlin, Berlin, Germany
- 3. Institute for Neurophysiology, Charité--Universitätsmedizin Berlin, Berlin, Germany
- 4. Institute of Biology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
- 5. Center for Behavioral Brain Sciences, Magdeburg, Germany
- 6. Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany
- 7. Institute of Radiology, Suedharz Hospital Nordhausen, Nordhausen, Germany
- 8. Institute of Molecular and Cell Biology, University of Applied Sciences Mannheim, Mannheim, Germany.
- 折叠
摘要
Abstract
A traumatic childhood is among the most important risk factors for developing stress-related psycho-pathologies such as posttraumatic stress disorder or depression later in life. However, despite the proven role of astrocytes in regulating transmitter release and synaptic plasticity, the contribution of astrocytic transmitter metab-olism to such stress-induced psychopathologies is currently not understood. In rodents, childhood adversity can be modeled by juvenile stress exposure, resulting in increased anxiety, and impaired coping with stress in adult-hood. We describe that such juvenile stress in rats, regardless of additional stress in adulthood, leads to reduced synaptic efficacy in the ventral CA1 (vCA1) Schaffer collaterals, but increased long-term potentiation (LTP) of synaptic transmission after high-frequency stimulation. We tested whether the glutamate-glutamine-cycle guides the lasting changes on plasticity observed after juvenile stress by blocking the astrocytic glutamate-degrading en-zyme, glutamine synthetase (GS). Indeed, the pharmacological inhibition of GS by methionine sulfoximine in slices from na?ve rats mimics the effect of juvenile stress on vCA1-LTP, while supplying glutamine is sufficient to normalize the LTP. Assessing steady-state mRNA levels in the vCA1 stratum radiatum reveals distinct shifts in the expression of GS, astrocytic glutamate, and glutamine transporters after stress in juvenility, adulthood, or com-bined juvenile/adult stress. While GS mRNA expression levels are lastingly reduced after juvenile stress, GS pro-tein levels are maintained stable. Together our results suggest a critical role for astrocytes and the glutamate-gluta-mine cycle in mediating long-term effects of juvenile stress on plasticity in the vCA1, a region associated with anxiety and emotional memory processing.关键词
星形胶质细胞/谷氨酸-谷氨酰胺循环/谷氨酰胺合成酶/青少年应激/长时程增强/腹侧海马Key words
astrocytes/glutamate-glutamine cycle/glutamine synthetase/juvenile stress/LTP/ventral hippo-campus分类
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Ivens S,Çalışkan,Papageorgiou I,Cesetti T,Malich A,Kann O,Heinemann U,Stork O,Albrecht A..青少年应激引起腹侧海马长时程增强的持续增加:星形细胞谷氨酰胺合成酶的作用[J].神经损伤与功能重建,2019,14(11):595,1.
