Age-Dependent Neuroimmune Modulation of IGF-1R in the Traumatic Mice

作者：Zhao Hui^*; Zhao Xiaocong; Cao Xiaoding; Wu Gencheng

来源：Immunity and Ageing, 2012, 9(1): 12.

DOI：10.1186/1742-4933-9-12

• IGF-1R
• Fyn
• Synapse
• Neuroimmune modulation
• MOR

Background: Age-dependent neuroimmune modulation following traumatic stress is accompanied by discordant upregulation of Fyn signaling in the frontal cortex, but the mechanistic details of the potential cellular behavior regarding IGF-1R/Fyn have not been established.
Methods: Trans-synaptic IGF-1R signaling during the traumatic stress was comparably examined in wild type, Fyn (-/-) and MOR (-/-) mice. Techniques included primary neuron culture, in vitro kinase activity, immunoprecipitation, Western Blot, sucrose discontinuous centrifugation. Besides that, [H-3] incorporation was used to assay lymphocyte proliferation and NK cell activity.
Results: We demonstrate robust upregulation of synaptic Fyn activity following traumatic stress, with higher amplitude in 2-month mice than that in 1-year counterpart. We also established that the increased Fyn signaling is accompanied by its molecular connection with IGF-1R within the synaptic zone. Detained analysis using Fyn (-/-) and MOR (-/-) mice reveal that IGF-1R/Fyn signaling is governed to a large extent by mu opioid receptor ( MOR), and with age-dependent manner; these signaling cascades played a central role in the modulation of lymphocyte proliferation and NK cell activity.
Conclusions: Our data argued for a pivotal role of synaptic IGF-1R/Fyn signaling controlled by MOR downstream signaling cascades were crucial for the age-dependent neuroimmune modulation following traumatic stress. The result here might present a new quality of synaptic cellular communication governing the stress like events and have significant potential for the development of therapeutic approaches designed to minimize the heightened vulnerability during aging.

• 出版日期2012-5-28
• 单位复旦大学