Death of adrenocortical cells during murine acute T. cruzi infection is not associated with TNF-R1 signaling but mostly with the type II pathway of Fas-mediated apoptosis

Pérez, Ana Rosa; Lambertucci, Flavia; González, Florencia Belén; Roggero, Eduardo; Meis, Juliana de; Ronco, Marı́a Teresa; Villar, Silvina Raquel

doi:10.1016/j.bbi.2017.05.017

Cited by 8 publications

(3 citation statements)

References 64 publications

(84 reference statements)

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“…The Fas/FasL system plays an important role in apoptosis during the acute phase in other neurological disorders, and our findings are in agreement with previous studies ( Furuichi et al, 2012 ; Tiao et al, 2014 ; Perez et al, 2017 ; Zhao et al, 2021 ). In a mouse model of traumatic brain injury, a peak in the levels of expression of Fas was noticed in the cortex and hippocampus 24 h after the injury ( Grosjean et al, 2007 ).…”

Section: Discussionsupporting

confidence: 94%

Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury

Lee

Song

Hwang

et al. 2023

Front. Mol. Neurosci.

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Appropriate rehabilitation of stroke patients at a very early phase results in favorable outcomes. However, the optimal strategy for very early rehabilitation is at present unclear due to the limited knowledge on the effects of very early initiation of rehabilitation based on voluntary exercise (VE). Environmental enrichment (EE) is a therapeutic paradigm for laboratory animals that involves complex combinations of physical, cognitive, and social stimuli, as well as VE. Few studies delineated the effect of EE on apoptosis in very early stroke in an experimental model. Although a minimal benefit of early rehabilitation in stroke models has been claimed in previous studies, these were based on a forced exercise paradigm. The aim of this study is to determine whether very early exposure to EE can effectively regulate Fas/FasL-mediated apoptosis following hypoxic–ischemic (HI) brain injury and improve neurobehavioral function. C57Bl/6 mice were housed for 2 weeks in either cages with EE or standard cages (SC) 3 h or 72 h after HI brain injury. Very early exposure to EE was associated with greater improvement in motor function and cognitive ability, reduced volume of the infarcted area, decreased mitochondria-mediated apoptosis, and decreased oxidative stress. Very early exposure to EE significantly downregulated Fas/FasL-mediated apoptosis, decreased expression of Fas, Fas-associated death domain, cleaved caspase-8/caspase-8, cleaved caspase-3/caspase-3, as well as Bax and Bcl-2, in the cerebral cortex and the hippocampus. Delayed exposure to EE, on the other hand, failed to inhibit the extrinsic pathway of apoptosis. This study demonstrates that very early exposure to EE is a potentially useful therapeutic translation for stroke rehabilitation through effective inhibition of the extrinsic and intrinsic apoptotic pathways.

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Section: Discussionsupporting

confidence: 94%

Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury

Lee

Song

Hwang

et al. 2023

Front. Mol. Neurosci.

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“…Recent studies have demonstrated the importance of the CD95/CD95L pathway to the nervous system, which is involved in the occurrence and development of a variety of neurological diseases such as AD, [38][39][40][41] but whether it is associated with neuropathic pain is not clear. The main function of CD95/CD95L is to participate in the immune response, etc.…”

Section: Discussionmentioning

confidence: 99%

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

et al. 2020

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Objectives: To explore the effects of trigeminal neuralgia on neurodegeneration in rats and the underlining mechanism. Methods: Sixty adult male Sprague Dawley rats were divided randomly into Chronic Constriction Injury of the Rat's Infraorbital Nerve (ION-CCI) group and sham group (n ¼ 30). Right suborbital nerve was ligated in ION-CCI group to establish a trigeminal neuralgia model. In sham group, suborbital nerve was exposed without ligation. Pain thresholds were measured before surgery and 1, 7, 15, and 30 days after surgery (n ¼ 10). Morris water maze tests (n ¼ 10) were conducted at 1, 15, and 30 days after surgery to evaluate the changes in learning and memory ability of rats. At 5, 19, and 34 days after surgery, serum S100b protein concentration and hippocampal Ab1-42 protein expression were detected by enzyme-linked immunosorbent assay; total tau protein expression was detected by Western blotting; changes of neurons in hippocampus were observed by Nissl staining; and the expression of ser404 p-tau, cluster of differentiation (CD)95, CD95L, and cleaved caspase-3 proteins was detected by immunofluorescence and Western blotting. Results: Hyperalgesia occurred in ION-CCI group, and mechanical pain threshold decreased significantly (P < 0.05). On the 15th and 30th days after surgery, ION-CCI group showed lower learning and memory ability than sham group (P < 0.05). Serum S100b protein concentration, hippocampal A b1-42, and ser404 p-tau protein expression increased in the ION-CCI group 19 and 34 days after surgery (P < 0.05), hippocampal CD95 expression increased in the ION-CCI group after surgery (P < 0.05), hippocampal CD95L expression increased at 19 and 34 days after surgery (P < 0.05), and cleaved caspase-3 expression increased at 5 and 19 days after surgery (P < 0.05). Nissl bodies in ION-CCI group decreased significantly at 15 days after surgery. The expression of cleaved caspase-3 protein in ION-CCI group was positively correlated with the expression of CD95 and CD95L (P < 0.05). Conclusions: Trigeminal neuralgia may lead to neuronal inflammation and neuronal apoptosis associated with upregulation of CD95/CD95L expression, thus causing neurodegeneration.

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“…Adrenal glands were homogenized in 4 volumes of 300 mmol/L sucrose with 1× protease inhibitor cocktail and 1× phosphatase inhibitor cocktail (SIGMA, Saint Louis, USA). Homogenates were centrifuged at 1,000g to remove unbroken cells, nuclei, and heavy membranes, based on previous studies (35). Proteins were quantified according to Lowry technique (36).…”

Section: Immunoblot Assaysmentioning

confidence: 99%

Evidence in Favor of an Alternative Glucocorticoid Synthesis Pathway During Acute Experimental Chagas Disease

et al. 2020

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It is well-established that infectious stress activates the hypothalamus-pituitary-adrenal axis leading to the production of pituitary adrenocorticotropin (ACTH) and adrenal glucocorticoids (GCs). Usually, GC synthesis is mediated by protein kinase A (PKA) signaling pathway triggered by ACTH. We previously demonstrated that acute murine Chagas disease courses with a marked increase of GC, with some data suggesting that GC synthesis may be ACTH-dissociated in the late phase of this parasitic infection. Alternative pathways of GC synthesis have been reported in sepsis or mental diseases, in which interleukin (IL)-1β, prostaglandin E2 (PGE2), and/or cAMP-activated guanine nucleotide exchange factor 2 (EPAC2) are likely to play a role in this regard. Accordingly, we have searched for the existence of an ACTH-independent pathway in an experimental model of a major parasitic disease like Chagas disease, in addition to characterizing potential alternative pathways of GC synthesis. To this end, C57BL/6 male mice were infected with T. cruzi (Tc), and evaluated throughout the acute phase for several parameters, including the kinetic of GC and ACTH release, the adrenal level of MC2R (ACTH receptor) expression, the p-PKA/PKA ratio as ACTH-dependent mechanism of signal transduction, as well as adrenal expression of IL-1β and its receptor, EPAC2 and PGE2 synthase. Our results reveal the existence of two phases involved in GC synthesis during Tc infection in mice, an initial one dealing with the well-known ACTH-dependent pathway, followed by a further ACTH-hyporesponsive phase. Furthermore, inflamed adrenal microenvironment may tune the production of intracellular mediators that also operate upon GC synthesis, like PGE2 synthase and EPAC2, as emerging driving forces for GC production in the advanced course of Tc infection. In essence, GC production seems to be associated with a biphasic action of PGE2, suggesting that the effect of PGE2/cAMP in the ACTH-independent second phase may be mediated by EPAC2.

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Death of adrenocortical cells during murine acute T. cruzi infection is not associated with TNF-R1 signaling but mostly with the type II pathway of Fas-mediated apoptosis

Cited by 8 publications

References 64 publications

Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury

Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

Evidence in Favor of an Alternative Glucocorticoid Synthesis Pathway During Acute Experimental Chagas Disease

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