Adenosine and Neopterin Levels in Cerebrospinal Fluid of Patients with Neurological Disorders.

Yoshida, Yasuhiko; Une, Fumiho; Utatsu, Yasuhiko; Nomoto, Masahiro; Furukawa, Yoshitaka; Maruyama, Yoshikazu; Machigashira, Naoko; Matsuzaki, Takashi; Osame, Mitsuhiro

doi:10.2169/internalmedicine.38.133

Cited by 35 publications

(24 citation statements)

References 41 publications

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“…Short duration of disease (!4.5 years) is characterized pathologically by "active chronic" CNS lesions, featuring marked inflammatory changes; an equitable distribution of CD4 ϩ and CD8 ϩ cells and macrophages; increased expression of IL-1b, TNF-a, and IFN-g; and frequent distribution of cytotoxic T cells and NK cells, immune system cells that target intracellular pathogens [3]. The significantly increased neopterin level among these patients is consistent with results obtained from Japanese HAM/TSP patients and indicates immune activation in the CNS [12].…”

Section: Discussionsupporting

confidence: 84%

Central Nervous System Activation of the Indoleamine‐2,3‐Dioxygenase Pathway in Human T Cell Lymphotropic Virus Type I–Associated Myelopathy/Tropical Spastic Paraparesis

et al. 2000

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Human T cell lymphotropic virus type I (HTLV-I) is associated with a chronic neurologic disease called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The potential mechanisms of HAM/TSP pathogenesis were assessed by examination of 2 pathways initiated by interferon-gamma, a predominant cytokine in HAM/TSP. Jamaican HAM/TSP patients (n=17) were compared with patients with other neurologic diseases (ONDs; n=13) with respect to cerebrospinal fluid levels of the following: neopterin; nitrite plus nitrate, a stable indicator of nitric oxide; and tryptophan and kynurenine, metabolites of the indoleamine-2,3-dioxygenase (IDO) pathway. HAM/TSP patients had significantly elevated levels of neopterin (P=.003) and kynurenine (P=.05) and a significantly decreased level of tryptophan (P=.003), compared with patients with ONDs. These results support immune activation within the central nervous system and activation of the IDO pathway. Thus, activation of the IDO pathway may play a role in HAM/TSP.

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Section: Discussionsupporting

confidence: 84%

Central Nervous System Activation of the Indoleamine‐2,3‐Dioxygenase Pathway in Human T Cell Lymphotropic Virus Type I–Associated Myelopathy/Tropical Spastic Paraparesis

et al. 2000

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“…In pathological conditions, extracellular adenosine levels are often significantly elevated (Yoshida et al, 1999), as neurons lose their structural integrity during degeneration and glia become reactive in response to neuronal degeneration. We have observed increased release of ATP from cultured SOD1G93A + astrocytes (Kawamata et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Adenosine levels are also significantly elevated in the cerebrospinal fluid (CSF) of progressing human ALS patients (Yoshida et al, 1999). Here we investigated the role of A 2a R-mediated adenosine signaling in motor neuron cell death and ALS-related motor phenotypes using both in vitro and in vivo models with complementary genetic and pharmacological approaches.…”

Section: Introductionmentioning

confidence: 99%

Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis

Higashimori

Tolman

et al. 2015

Experimental Neurology

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Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease in which the majority of upper and lower motor neurons are degenerated. Despite intensive efforts to identify drug targets and develop neuroprotective strategies, effective therapeutics for ALS remains unavailable. The identification and characterization of novel targets and pathways remain crucial in the development of ALS therapeutics. Adenosine is a major neuromodulator that actively regulates synaptic transmission. Interestingly, adenosine levels are significantly elevated in the cerebrospinal fluid (CSF) of progressing human ALS patients. In the current study, we showed that adenosine 2a receptor (A2aR), but not adenosine 1 receptor (A1R), is highly enriched in spinal (motor) neurons. A2aR expression is also selectively increased at the symptomatic onset in the spinal cords of SOD1G93A mice and end-stage human ALS spinal cords. Interestingly, we found that direct adenosine treatment is sufficient to induce embryonic stem cell-derived motor neuron (ESMN) cell death in cultures. Subsequent pharmacological inhibition and partial genetic ablation of A2aR (A2aR+/−) significantly protect ESMN from SOD1G93A+ astrocyte-induced cell death and delay disease progression of SOD1G93A mice. Taken together, our results provide compelling novel evidence that A2aR-mediated adenosine signaling contributes to the selective spinal motor neuron degeneration observed in the SOD1G93A mouse model of ALS.

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“…Anti-neural antibodies against GM1-gangliosides, asialo-GM1-gangliosides and sulfatides : Immune response; activation of microglia (Moreau et al 2005;Ganesalingam et al 2011;Goldknopf et al 2006;Sekizawa et al 1998;Tsuboi and Yamada 1994;Yoshida et al 1999;Tanaka et al 2006;Glabinski et al 1997;Graves et al 2004;Wilms et al 2003;Almer et al 2002;Mitchell et al 2009;McGeer and McGeer 2002;Niebroj-Dobosz et al 1999) Glial activation markers Erythropoietin (EPO) ; A neurotrophic factor (Brettschneider et al 2006d) S100b…”

Section: Dysfunction Of the Bbb/bscb/bcsfb And Its Markers In Csfmentioning

confidence: 99%

“…In the CSF, increased concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), complement factors C3 and C4, peroxynitrite, prostaglandin E2, neopterin, monocyte chemoattractant protein-1 (MCP-1), granulocyte colony stimulating factor (G-CSF) and antibodies against various cellular structures have been reported (Almer et al 2002;Ganesalingam et al 2011;Goldknopf et al 2006;Graves et al 2004;McGeer and McGeer 2002;Mitchell et al 2009;Moreau et al 2005;Sekizawa et al 1998;Tanaka et al 2006;Tsuboi and Yamada 1994;Yoshida et al 1999;Glabinski et al 1997;Wilms et al 2003).…”

Section: Markers Of Inflammation and Immune Activation In Csfmentioning

confidence: 99%

CSF markers in amyotrophic lateral sclerosis

et al. 2012

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Amyotrophic lateral sclerosis (ALS, 'Lou Gehrig disease') is the most common, progressive, neurodegenerative, motor neuron disease, causing damage to upper and lower motor neurons, leading to paralysis and death within 3-5 years. Majority of ALS cases are sporadic ALS (SALS) and only 5-10 % of cases are familial ALS (FALS). Pathogenesis of ALS is complicated and still unclear, including genetic, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, neurofilament accumulation, impaired trophic support, altered glial function, viral infection, immune imbalance and impairment of the blood-brain, blood-spinal cord and blood-cerebrospinal fluid barriers (BBB/BSCB/BCSFB). The CSF analysis is still one of the basic laboratory tools and might reflect pathophysiological alterations in the course of the disease and could provide an insight into disease pathomechanisms. The most important aim of its analysis is evaluation of blood-CSF barrier, which is altered in 46 % of ALS patients. The CSF biomarkers may give insight into ALS pathophysiology and may be useful for early, presymptomatic diagnosis, therapeutic monitoring and the development of new therapeutic strategies. This review summarizes the general concepts of biomarkers in CSF of ALS patients and their potential usefulness in further research.

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Adenosine and Neopterin Levels in Cerebrospinal Fluid of Patients with Neurological Disorders.

Cited by 35 publications

References 41 publications

Central Nervous System Activation of the Indoleamine‐2,3‐Dioxygenase Pathway in Human T Cell Lymphotropic Virus Type I–Associated Myelopathy/Tropical Spastic Paraparesis

Central Nervous System Activation of the Indoleamine‐2,3‐Dioxygenase Pathway in Human T Cell Lymphotropic Virus Type I–Associated Myelopathy/Tropical Spastic Paraparesis

Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis

CSF markers in amyotrophic lateral sclerosis

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