Letter to the EditorKuehne LK, Reiber H, Bechter K, Hagberg L, Fuchs D., Cerebrospinal fluid neopterin is brain-derived and not associated with blood-CSF barrier dysfunction in non-inflammatory affective and schizophrenic spectrum disorders. Journal of Psychiatric Research, Volume 47, Issue 10, October 2013, Pages 1417–1422
Section snippets
Role of funding source
The authors declare that the work was performed without particular funding.
Contributors
Ghisoni K., PhD student, performed experiments and analyzed samples.
Latini A., senior researcher, supervised all experiments and the manuscript.
Conflict of interest
We declare no conflict of interest.
Acknowledgment
The authors are grateful to Theodore Griswold for language editing. This work was supported by grants from FAPESC (Fundação de Apoio à Pesquisa Científica e Tecnológica do Estado de Santa Catarina), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), INCT for Excitotoxicity and Neuroprotection-MCT/CNPq, IBN.Net/CNPq, and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). Latini A is a CNPq fellow.
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Cerebrospinal fluid neopterin is brain-derived and not associated with blood-CSF barrier dysfunction in non-inflammatory affective and schizophrenic spectrum disorders
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2019, Physiology and BehaviorCitation Excerpt :In addition, neopterin is secreted in human primary neurons and mouse CNS cells under LPS inflammatory stimulus [30]. However, under a non-inflammatory scenario, neopterin has neuroprotective activities, i.e. neopterin is a cognitive enhancer, has antioxidant and anti-inflammatory properties, and increases mitochondrial brain activity [11,29,35,69,70]. It is widely known, that all these cytoprotective mechanisms are also induced by the regular practice of moderate intensity physical exercise.
Tetrahydrobiopterin improves hippocampal nitric oxide-linked long-term memory
2018, Molecular Genetics and MetabolismCitation Excerpt :Furthermore, we have demonstrated that neopterin is formed and released by rodent and human nerve cells under cellular stress [5, 10]. In addition, we have also demonstrated that that after a single neopterin intracerebroventricular administration, resistance to oxidative damage by activating the antioxidant Nrf2/ARE-linked pathway is promoted [5, 11], inflammation is reduced [5], the activation of inflammasome is inhibited [10], and cognition is enhanced in rodents [12]. Since neopterin is a byproduct of the de novo pathway, and increased levels of neopterin will occur together with increased BH4 levels, we hypothesize that BH4 induces similar positive effects in the brain.
Neopterin preconditioning prevents inflammasome activation in mammalian astrocytes
2018, Free Radical Biology and MedicineCitation Excerpt :The reduction production of lactate might result from increased phosphate pentose pathway to sustain increased glutathione peroxidase/glutathione reductase activity. Indeed, we also reported increased activity of glutathione peroxidase/glutathione reductase, and well as, increased levels of glutathione in brain from naïve mice treated intracerebroventricularly with neopterin [23]. Two systems required for hydrogen peroxide detoxification.
Neopterin acts as an endogenous cognitive enhancer
2016, Brain, Behavior, and ImmunityCitation Excerpt :Neopterin production by the central nervous system (CNS) has recently been proposed by Kuehne et al. (2013) based on observations that neopterin concentrations in cerebrospinal fluid were higher than those in serum from patients suffering from schizophrenic spectrum disorders with no blood-brain barrier dysfunction. In addition, our group demonstrated that in both rat striatal astrocytes and hippocampal slices neopterin was synthesized and release under cellular stress conditions (Ghisoni and Latini, 2015). However, the exact physiological role of the biology of this pteridine, even in the periphery is virtually unknown.
Neopterin as a potential cytoprotective brain molecule
2015, Journal of Psychiatric ResearchCitation Excerpt :In agreement, Kuehne et al. (2013) found a lack of correlation between CSF and serum neopterin levels from psychiatric patients with normal barrier function (CSF 7.4 nmol/L; serum 4.9 nmol/L) and blood-CSF barrier dysfunction (CSF 8.9 nmol/L; serum 6.6 nmol/L), supporting an independent local and central synthesis of the pterin (Kuehne et al., 2013). Additionally, our group has shown, by using a mitotoxic brain tissue-based experimental system, that neopterin is also produced by local nerve cells under stressful conditions (Ghisoni and Latini, 2015). Considering that microglial cells, which represent about 10% of the nervous cells, belong to the monocyte/macrophage lineage, these cells are candidates to produce neopterin.