Characterization of Fyn signaling on the age-dependent immuno-modulation on traumatic rats

Xiao, Sheng; Wang, Jun; Jiang, Jinju; Cao, Xiao-Ding; Zhao, Hui

doi:10.1016/j.brainres.2008.12.007

Cited by 5 publications

(8 citation statements)

References 22 publications

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“…Ultimately, reductions in synaptic numbers and the amplitude of the field excitatory postsynaptic potential (EPSP) happened during the aging [31]. In the present study, we demonstrated that synaptic Fyn activity was greatly augmented at day 3after trauma, with higher magnitude in 1-year mice that that in 2-month counterpart, together with our previous observation, namely, discordant Fyn signaling events was responsible for the deteriorated immuno-suppression and prolonged recovery aged rats during the traumatic stress [8,32], then, the result reinforced the idea that Fyn signaling might actively communicate with pre and post-synaptic elements of neuronal terminals influencing stress like events.…”

Section: Discussionsupporting

confidence: 74%

“…Our previous observation confirmed this realization that when challenged with traumatic stress, 1-year rats displayed deteriorated immuno-suppression and prolonged recovery than 3-month counterpart. The major hypothesis has been proposed Fyn, a member of Src-family protein tyrosine kinase, as an explanation, whose age-dependent expression was responsible for the related cellular responses induced by traumatic stress, and presumed to be crucial for the resolution of this stressful event [8]. …”

Section: Introductionmentioning

confidence: 99%

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

Zhao

Cao

2012

Immun Ageing

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BackgroundAge-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.MethodsTrans-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.ResultsWe 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.ConclusionsOur 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.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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

Zhao

Cao

2012

Immun Ageing

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“…Importantly, neuroimmune modulation following surgical stress has been ascribed to molecular events taking place in cortical circuits. These can be separated into two stages - early events of immunosuppresion operating through an elaborate IL-1β pathway [ 8 - 13 ], and later progression marked by changes in c-Src signaling [ 14 ]. These dynamic alterations are likely to take place in distinct cellular compartments controlling the activation of different signaling cascades.…”

Section: Introductionmentioning

confidence: 99%

“…c-Src function is crucial for recovery from traumatic stress-mediated immunosuppression [ 14 ], but its mechanistic linkage to inflammation onset and progression remains to be elucidated. c-Src is a member of the Src family of protein kinases whose members play a crucial role in transducing extracellular signals to cytoplasmic and nuclear effectors, and thereby regulate a wide variety of cellular functions, including cell proliferation, differentiation and stress responses [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroimmune modulation following traumatic stress in rats: evidence for an immunoregulatory cascade mediated by c-Src, miRNA222 and PAK1

Zhao

Yao

Cao

2011

J Neuroinflammation

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BackgroundNeuroimmune modulation following traumatic stress is accompanied by cortical upregulation of c-Src expression, but the mechanistic details of the potential regulatory link between c-Src expression and immunosuppression have not been established.MethodsWe used a combination of techniques to measure temporal changes in: (i) the parallel expression of c-Src and microRNA222; (ii) levels of PAK1 (p21-activated kinase 1); and (iii) the association between PAK1 and interleukin 1β signaling, both in cortex of rats following traumatic stress and in primary cortical neurons. Techniques included real-time PCR, immunoprecipitation, western blotting and subcellular fractionation by discontinuous centrifugation. We also measured lymphocyte proliferation and natural killer (NK) cell activity.ResultsWe confirm robust upregulation of c-Src expression following traumatic stress. c-Src upregulation was accompanied by marked increases in levels of miRNA222; other studied miRNAs were not affected by stress. We also established that PAK1 is a primary target for miRNA222, and that increased levels of miRNA222 following traumatic stress are accompanied by downregulation of PAK1 expression. PAK1 was shown to mediate the association of IL-1RI with lipid rafts and thereby enhance IL-1 signaling. Detailed analyses in cultured neurons and glial cells revealed that PAK1-mediated enhancement of IL-1RI activation is governed to a large extent by c-Src/miRNA222 signaling; this signaling played a central role in the modulation of lymphocyte proliferation and NK cell activity.ConclusionsOur results suggest that neuroimmune modulation following traumatic stress is mediated by a cascade that involves c-Src-mediated enhancement of miRNA222 expression and downregulation of PAK1, which in turn impairs signaling via IL-1β/IL1-RI, leading to immunosuppression. The regulatory networks involving c-Src/miRNA222 and PAK1/IL-1RI signaling have significant potential for the development of therapeutic approaches designed to promote recovery following traumatic injury.

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“…Trauma not only destroys healthy body tissue, but can also lead to the development of functional disorders within the nerve-endocrine-immune system. Therefore, traumatic stress was used as a stressor in our previous study, which indicated that immunosuppression is accompanied by a decrease in splenocyte proliferation and natural killer cell activity 1-3 days post-trauma; however, complete recovery was observed by day 7 (8). Furthermore, inflammation induced by some factors, such as lipopolysaccharides, has been deemed to result in a persistent increase in alcohol self-administration (9,10).…”

Section: Introductionmentioning

confidence: 99%

Traumatic stress affects alcohol‑drinking behavior through cocaine‑ and amphetamine‑regulated transcript 55‑102 in the paraventricular nucleus in rats

Liu

et al. 2017

Mol Med Report

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Cumulative evidence has suggested an association between stress and alcohol self‑administration; however, less is known about the role of traumatic stress in alcohol drinking behavior. It has been reported that cocaine‑ and amphetamine‑regulated transcript (CART) 55‑102 may be involved in mediating stress responses and regulating reward and reinforcement. The aim of the present study was to evaluate the role of CART 55‑102 in alcohol drinking behavior of rats in the presence or absence of traumatic stress. Alcohol drinking behavior was examined using the two‑bottle choice drinking paradigm (one bottle contained 10% alcohol and the other contained filtered water), which was initiated 1, 3 and 7 days post‑trauma (T1, T3 and T7), for 14 days in rats; the control group was initiated from T0. The results indicated that exposure to trauma significantly increased alcohol consumption and preference, particularly drinking from T3. Immunohistochemistry revealed that the lowest level of CART 55‑102 immunoreactivity within the paraventricular nucleus (PVN) was exhibited in the T3 group. Additionally, an intra‑PVN injection of CART 55‑102 attenuated alcohol‑drinking behavior in a dose‑dependent manner, in the T3 group. Furthermore, the significant increase in circulating adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) concentrations in the T3 group were inhibited by CART 55‑102 administration to the PVN, in particular CORT levels were significantly decreased. Positive correlations between alcohol preference and ACTH and CORT levels were also observed. These results indicated that CART 55‑102 in the PVN serves an inhibitory role in traumatic stress‑induced alcohol drinking behavior, possibly through disturbing hypothalamus‑pituitary‑adrenal axis hyperactivity.

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Characterization of Fyn signaling on the age-dependent immuno-modulation on traumatic rats

Cited by 5 publications

References 22 publications

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

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

Neuroimmune modulation following traumatic stress in rats: evidence for an immunoregulatory cascade mediated by c-Src, miRNA222 and PAK1

Traumatic stress affects alcohol‑drinking behavior through cocaine‑ and amphetamine‑regulated transcript 55‑102 in the paraventricular nucleus in rats

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