Induction of Ucp2 expression in brain phagocytes and neurons following murine toxoplasmosis: An essential role of IFN-γ and an association with negative energy balance

Arsenijevic, Denis; Clavel, S.; Sanchı́s, Daniel; Plamondon, Julie; Huang, Quingling; Ricquier, Daniel; Rouger, Laurie; Richard, Denis

doi:10.1016/j.jneuroim.2007.03.013

Cited by 15 publications

(9 citation statements)

References 52 publications

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“…In the same line with this idea, our contributions have shown that both UCP2 and SOCS-3 mRNA levels in brains infected with Toxoplasma gondii were elevated in microglia (Arsenijevic et al, 2007a). Although we cannot exclude a possible participation of infiltrated leukocytes, our evidence suggests that GSH, UCP2 and SOCS-3 may attenuate ischemic injury in infected mice by modifying microglia activity.…”

Section: Discussionsupporting

confidence: 80%

“…Brain slices (20 m) were stained with hematoxylin and eosin for histological identification of Toxoplasma gondii cysts and infiltrating immune cells (Frenkel and Escajadillo, 1987;Arsenijevic et al, 2007a). Detection of apoptosis in the brain of chronically infected mice was made using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) labeling as previously described (de Bilbao et al, 2000).…”

Section: Histology Of Infected Brains Compared With Non-infected Contmentioning

confidence: 99%

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Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

et al. 2007

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Abstract-To determine whether Toxoplasma gondii infection could modify biological phenomena associated with brain ischemia, we investigated the effect of permanent middle cerebral artery occlusion (MCAO) on neuronal survival, inflammation and redox state in chronically infected mice. Infected animals showed a 40% to 50% decrease of infarct size compared with non-infected littermates 1, 4 and 14 days after MCAO. The resistance of infected mice may be associated with increased basal levels of anti-inflammatory cytokines and/or a marked reduction of the MCAO-related brain induction of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma (IFN␥). In addition, potential anti-inflammatory/neuroprotective factors such as nerve growth factor, suppressor of cytokine signaling-3, superoxide dismutase activity, uncoupling protein-2 and glutathione (GSH) were upregulated in the brain of infected mice. Consistent with a role of GSH in central cytokine regulation, GSH depletion by diethyl maleate inhibited Toxoplasma gondii lesion resistance by increasing the proinflammatory cytokine IFN␥ brain levels. Overall, these findings indicate that chronic toxoplasmosis decisively influences both the inflammatory molecular events and outcome of cerebral ischemia.

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Section: Discussionsupporting

confidence: 80%

Section: Histology Of Infected Brains Compared With Non-infected Contmentioning

confidence: 99%

Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

et al. 2007

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“…A protective function for UCP2 has been proposed for a range of diseases, such as ischemia [26], [32], brain trauma [32], epilepsy [58]–[60], Parkinson’s disease [61], diabetes [18], obesity [62], and anorexia nervosa [63]. Interestingly, not only brain degenerative processes, as previously noted [64], but also all other pathophysiological models listed above have a strong immunological background, accompanied by a massive invasion of activated lymphocytes or the activation of phagocytes/microglia [65]. Unfortunately, the proper discrimination of UCP2 expression in different cell types and in restricted areas remains a difficult task, because to date there are no antibodies suitable for the immunohistochemical analysis.…”

Section: Discussionmentioning

confidence: 87%

Quantification of Uncoupling Protein 2 Reveals Its Main Expression in Immune Cells and Selective Up-Regulation during T-Cell Proliferation

et al. 2012

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Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein. Although the protein was discovered in 1997, its function and even its tissue distribution are still under debate. Here we present a quantitative analysis of mRNA and protein expression in various mice tissues, revealing that UCP2 is mainly expressed in organs and cells associated with the immune system. Although the UCP2 gene is present in the brain, as demonstrated using quantitative RT-PCR, the protein was not detectable in neurons under physiological conditions. Instead, we could detect UCP2 in microglia, which act in the immune defense of the central nervous system. In lymphocytes, activation led to a ten-fold increase of UCP2 protein expression simultaneously to the increase in levels of other mitochondrial proteins, whereas lymphocyte re-stimulation resulted in the selective increase of UCP2. The highest detected level of UCP2 expression in stimulated T-cells (0.54 ng/(µg total cellular protein)) was approximately 200 times lower than the level of UCP1 in brown adipose tissue from room temperature acclimated mice. Both the UCP2 expression pattern and the time course of up-regulation in stimulated T-cells imply UCP2’s involvement in the immune response, probably by controlling the metabolism during cell proliferation.

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“…Under normal circumstances, UCP2 is expressed predominantly in neurons in several brain regions in both rodents and primates (Horvath et al, 1999; Arsenijevic et al, 2007), although microglia, resident monocytes of the brain (Bechmann et al, 2002), invading monocytes and neutrophils (Arsenijevic et al, 2007), and cells of the choroid plexus (Richard et al, 1999) also express this mitochondrial uncoupling protein. High levels of UCP2 expression have been shown to protect neonatal neurons from excitotoxic cell death by inhibiting reactive oxygen species production and preventing mitochondrial dysfunction (Sullivan et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma

Sharma¹,

Zhuang²,

Ying³

et al. 2009

Neuroscience

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Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery. Keywords curcumin; energy homeostasis; traumatic brain injury Traumatic brain injury (TBI) is associated with costly health problems and results in impairment of cognitive abilities. TBI involves large transient increases in excitatory neurotransmitter efflux (Biegon, 2004) resulting in excitotoxicity, ionic imbalance, ATP depletion, proteolysis, and oxidative stress (Ansari et al., 2008). TBI is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. Energy homeostasis is fundamental for the survival of both the cell and the organism. New research indicates that events that regulate energy homeostasis have crucial impact on synaptic function, and that this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The significance of Curcuma longa Linn (turmeric) in health and nutrition has changed considerably since the discovery of the antioxidant property of naturally occurring phenolic compounds, curcuminoids. Curcumin has numerous pharmacological activities like antiinflammatory activity, antiprotozoal activity, nematocidal activity, antibacterial activity, antimutagenic activity and hepatoprotective activity. A single epidemiological study suggested that curcumin, as one of the most prevalent nutritional and medicinal compounds used by the Indian population, is responsible for the reduced (4.4-fold) prevalence of Alz...

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Induction of Ucp2 expression in brain phagocytes and neurons following murine toxoplasmosis: An essential role of IFN-γ and an association with negative energy balance

Cited by 15 publications

References 52 publications

Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

Quantification of Uncoupling Protein 2 Reveals Its Main Expression in Immune Cells and Selective Up-Regulation during T-Cell Proliferation

Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma

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