Ida T, Hara M, Nakamura Y, Kozaki S, Tsunoda S, Ihara H. Cytokine-induced enhancement of calcium-dependent glutamate release from astrocytes mediated by nitric oxide. Neurosci Lett 432: 232-236
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka, Japan. Neuroscience Letters
(Impact Factor: 2.03).
03/2008; 432(3):232-6. DOI: 10.1016/j.neulet.2007.12.047
Cytokines are produced in the central nervous system (CNS) and exhibit various effects on neurons, microglia, and astrocytes. Astrocytes can release chemical transmitters, including glutamate, in a calcium-dependent manner, which may mediate communication between neurons and astrocytes. To date, no studies have been conducted on the effects of cytokines on calcium-dependent glutamate release from astrocytes. Here, we studied the effects of cytokines on calcium-dependent glutamate release. Cytokines enhanced glutamate release and induced the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO). The inhibition of iNOS eliminated the cytokine-induced enhancement of glutamate release, and treatment with a NO donor, even in the absence of cytokines, increased glutamate release. Thus, cytokines enhance glutamate release, and this enhancement is mediated by NO.
Available from: Andrew H Miller
- "Finally, cytokines and inflammation have been shown to increase glutamate by effects on astrocytes. A rich literature has shown that cytokines can decrease the astrocytic expression of glutamate transporters and increase astrocytic release of glutamate (Ida et al., 2008; Tilleux and Hermans, 2007). Of note, glutamate released by astrocytes has preferential access to extrasynaptic NMDA receptors, which lead to decreased production of trophic factors, including brain-derived neurotrophic factor, ultimately contributing to further disruption of neuronal integrity (Hardingham et al., 2002; Haydon and Carmignoto, 2006). "
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ABSTRACT: Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise.
Frontiers in Neuroendocrinology 08/2012; 33(3):315. DOI:10.1016/j.yfrne.2012.09.003 · 7.04 Impact Factor
Available from: Andrea Schreiberova
- "The results were statistically evaluated by ANOVA and the Tukey–Kramer test; * P \ 0.05 with respect to the control group; # P \ 0.05 with respect to 15 min ischemia and 2 weeks of reperfusion; IS ischemia; R reperfusion J Mol Hist (2012) 43:203–213 211 immunoreactivity in reactive astrocytes of lumbar spinal cord tissue from spastic animals. The recent studies have shown that cytokines enhanced glutamate release and induced the expression of inducible NOS in astrocytes to produce NO (Saha and Pahan 2006; Ida et al. 2008). It is known that certain interaction between activation of Ca 2? dependent NOS and Ca 2? -independent NOS (iNOS) in the tissue exists (Lukácová et al. 2006). "
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ABSTRACT: Spinal cord ischemia belongs to serious and relatively frequent diseases of CNS. The aim of the present study was to find out the vulnerability of nitrergic neurons to 15 min transient spinal cord ischemia followed by 1 and 2 weeks of reperfusion. We studied neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in structural elements of lumbosacral spinal cord along its rostrocaudal axis. In addition, a neurological deficit of experimental animals was evaluated. Spinal cord ischemia, performed on the rabbit, was induced by abdominal aorta occlusion using Fogarty catheter introduced into the right femoral artery for a period of 15 min. After surgical intervention the animals survived for 7 and 14 days. nNOS-immunoreactivity (nNOS-IR) was measured by immunohistochemical and NADPHd-positivity by histochemical method, and both immunohistochemical and histochemical stainings were quantified by densitometric analyses. Neurological deficit was evaluated according Zivin's criteria. The number of nNOS-IR and/or NADPH-d positive neurons and the density of neuropil were markedly increased in superficial dorsal horn (laminae I-III) after 15 min ischemia and 7 days of reperfusion. However, ischemia followed by longer time of survival (14 days) returned the number of nNOS-IR and NADPH-d positive neurons to control. In the pericentral region (lamina X) containing interneurons and crossing fibers of spinal tracts, than in lamina VII and in dorsomedial part of the ventral horn (lamina VIII) we recorded a decreased number of nNOS-IR and NADPH-d positive neurons after both ischemia/reperfusion periods. In the medial portion of lamina VII and dorsomedial part of the ventral horn (lamina VIII) we observed many necrotic loci. This area was the most sensitive to ischemia/reperfusion injury. Fifteen minute ischemia caused a marked deterioration of neurological function of hind limbs, often developing into paraplegia. A quantitative immunohistochemical and histochemical study have shown a strong vulnerability of nitrergic neurons in intermediate zone to transient spinal cord ischemia.
Journal of molecular histology 01/2012; 43(2):203-13. DOI:10.1007/s10735-011-9386-7 · 1.82 Impact Factor
Available from: onlinelibrary.wiley.com
- "However, when immune challenge becomes chronic and/or dysregulated, because of chronic medical illness, chronic stress, or cytokine treatments, the resultant chronic inflammatory response contributes to the development of maladaptive behavioural symptoms and neuropsychiatric disorders. Cytokines may lead to behavioural changes through their effects on: (i) neurotransmitter function: cytokines can alter the metabolism of serotonin, dopamine and glutamate (Moron et al., 2003; Cai et al., 2005; Ida et al., 2008); (ii) neuroendocrine activity: cytokines can alter the function of hypothalamic–pituitary–adrenal axis via stimulant effects on the expression and release of corticotropin-releasing hormone, adrenocorticotropic hormone and cortisol (Pariante and Miller, 2001; Raison et al., 2010); (iii) neurogenesis: cytokines may affect neurogenesis via activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) (Ben Menachem-Zidon et al., 2008); and (iv) neurocircuitry: the basal ganglia and subgenual and dorsal aspects of the anterior cingulate cortex are target regions of cytokines (Brydon et al., 2008; Miller, 2009). Behavioural consequences of these effects include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; all symptoms that overlap with those which characterize a range of neuropsychiatric disorders (Capuron and Miller, 2011). "
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ABSTRACT: Research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, the presence of inflammatory responses and the crucial role of cytokines in major depression have been addressed in numerous studies. However, neuroinflammatory hypotheses in anxiety disorders have been studied less extensively than in major depression. There is a high research need for better understanding of both the heterogeneous role of specific cytokines in the control of anxious states and in different anxiety disorders and of the immunomodulating effects of antidepressants on anxiety.
Relevant literature was identified through a search of MEDLINE via PubMed. We discuss recent research on neuroimmunology in anxiety and make methodological recommendations for future investigation of neuroinflammatory hypotheses in anxiety disorders.
Some accumulating evidence has indicated modulatory effects of cytokines on neuronal communication and anxiety; however, research has not revealed consistent reproducible findings.
The availability of inflammatory biomarkers may provide an opportunity to identify patients via specific pathophysiological processes and to monitor therapeutic responses within relevant pathways. Further understanding of the neuroimmunological mechanisms to untangle the reciprocal associations between inflammation and anxiety is warranted.
Human Psychopharmacology Clinical and Experimental 01/2012; 27(1):6-14. DOI:10.1002/hup.1259 · 2.19 Impact Factor
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