Age-Dependent Neuroimmune Modulation of IGF-1R in the Traumatic Mice.
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, [3 H] 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.
Department of Integrative Medicine and Neurobiology, National Key lab of Medical Neurobiology, Institute of Brain Research Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. mayzhao5375@yahoo.com.
Hui
H
Zhao
Xiaocong
X
Zhao
Xiaoding
X
Cao
Gencheng
G
Wu