Interleukin‐2 as a neurotrophic factor for supporting the survival of neurons cultured from various regions of fetal rat brain

Awatsuji, Hirofumi; Furukawa, Yoshiko; Nakajima, Miki; Furukawa, Shoei; Hayashi, Kyozo

doi:10.1002/jnr.490350310

Cited by 72 publications

(33 citation statements)

References 39 publications

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“…Brojna istraživanja na animalnm modelima potvrdjuju predpostavku da citokini utiču na neurotransmitersku aktivnost [19]. Simplifikovano, pojedini citokini koji se frekventno dovode u korelaciju sa shizofrenijom dovode do neurohemijskih promena u ovom oboljenju npr.-IL-6 stimuliše povećavanje serotonina i dovodi do mezokortikalne dopaminske aktivnosti u hipokampusu i prefrontalnom korteksu [20], TNF-a ima stimulatorni efekat na kateholamine u slučaju akutnog oslobadjanja, dok hronično utiče na inaktivaciju kateholaminske sekrecije [21], IL-2 stimuliše dopaminsku neurotransmisiju sa jedne strane, akutno administriran utiče i na povečanje noradrenalina na funkcionalno značajnim mestima, a sa druge strane utiče i na inhibiciju oslobadjanja acetilholina u hipokampusu i prefrontalnom korteksu [22,23]. Nezaobilazno je pomenuti da disbalans Th1/Th2 (u smislu prevage Th2 odgovora kod obolelih od shizofrenije) je usko povezan sa enzimom indolamin-2,3-dioksigenaze (IDO), metabolizmom triptofan/kinurenin i nizom reperkusija na sistem neurotransmisije naročito na dopaminergički,serotonergički i glutamatergički sistem.…”

Section: Uticaj Citokina Na Neurotransmisijuunclassified

Schizophrenia and cytokines

Dunjić-Kostić¹,

Pantović-Stefanović²,

Ivković³

et al. 2015

Engrami

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Razvoj sofisticiranih tehnika detekcije strukturnih i biohemijskih abnormlnosti, u poslednjih nekoliko decenija, odigrao je važnu ulogu u preciznijem sagledavanju brojnih bioloških alteracija kod pacijenata uopšte. Ova činjenica je od posebne važnosti istraživačima u oblasti neuronauka, zbog često nepoznate i/ili multifaktorijalne etiopatogeneze neuropsihijatrijskih poremećaja, te svaki deo spoznaje kompleksnog "algoritma" ima svoje značajno mesto. U poslednje vreme veliku pažnju istraživača privlače eksploracija imunoloških abnormalnosti kod obolelih od shizofrenije, kao i citokinima posredovani mehanizmi koji predstavljaju osnovu za niz hipoteza iznesenih na ovu temu [1][2][3]. U daljem tekstu fokusiraće-mo se na nekoliko najvažnijih teorijskih pravaca koje se tiču inflamacije i imunoloških promena zapaženih u shizofreniji. Jedna od teorija je da je infekcija majke tokom trudnoće (naročito tokom ranog perinatalnog perioda) značajan faktor rizika za dete za razvoj shizofrenije i drugih neurorazvojnih oboljenja [4,5]. Epidemiološke studije su pokazale da infekcija majke virusom influence tokom trudnoće povećava rizik za shizofreniju deteta za 3-7 puta [4,6]. Pored virusa influence i brojni drugi infektivni činioci su povezani sa povećanim rizikom za SCH medju kojima su i varicela zoster virus, polio, difterija, rubela itd [5]. Medjutim, patološki mehanizam odgovoran za povećan rizik za shizofreniju kod dece nakon izloženosti majke infekciji još uvek je nedovoljno jasan. Takodje otvoreno je pitanje, na koji način infekcija majke dovodi do citokinskog disbalansa kod fetusa; da li je u pitnju delovanje infektivnog činioca na specifične receptore koji dovode do produkcije i oslobadjanja različitih medijatora zapaljenja u periferni majčin imuni sistem koji onda prolaze placentu i ulaze u cirkulaciju fetusa [6,7], ili potencijalni iz- Kratak sadržajPoslednjih par decenija pažnju istraživača sve više privlače imunološke abnormalnosti uočene kod obolelih od shizofrenije. U prvom delu teksta prikazan je kratak pregled pojedinih teorijskih konstrukata predloženih u cilju boljeg uvida u povezanost shizofrenije i imunoloških alteracija, u drugom delu je razmotren uticaj citokina na pojedine neurotransmiterske sisteme i finalno izneta su zapažanja dobijena iz istraživanja u realnoj kliničkoj situaciji kao i pravci budućih istraživanja.

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Section: Uticaj Citokina Na Neurotransmisijuunclassified

Schizophrenia and cytokines

Dunjić-Kostić¹,

Pantović-Stefanović²,

Ivković³

et al. 2015

Engrami

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“…IL-2 supports the survival and enhances neurite extension of cultured hippocampal neurons prepared from fetal rat brain. IL-2 also supports the survival of cultured cortical, striatal, and septal neurons, but does not act as a differentiation factor for striatal cholinergic neurons [40].…”

Section: Effects Of Il-2 On Neuron and Glial Cellsmentioning

confidence: 99%

Interleukin-2 and Its Effects in the Central Nervous System

Jiang

Lu²

1998

Biol Signals Recept

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Interleukin-2 (IL-2) is not only an important immunoregulatory molecule: it is also an important neuroregulatory molecule in the CNS. Investigations in vivo and in vitro have elucidated the following: IL-2 and IL-2 receptors (IL-2R) have been detected in the brain; IL-2 promotes survival and neurite extension of cultured neurons, stimulates oligodendrocyte proliferation and maturation, affects the hypothalamic-pituitary function and produces behavioral and electrocorticogram spectrum changes. Investigations in some laboratories, including ours, have also demonstrated an analgesic effect of IL-2 in the CNS. The molecular structure of the analgesic domain of IL-2 is distinct from the immune domain mediating immunoregulatory effects. A possible mechanism of action of cytokines on the CNS and the immune system or both exists: multiple actions of cytokines could be mediated by distinct domains or functional sites of cytokines interacting with different receptors or receptor subtypes.

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“…It has been shown that some interleukins (such as IL-1, IL-2, IL-3, IL-4, IL-6, IL-7 and IL-8) promote the neuritogenesis and induce the differentiation of several neuronal populations in vitro [21,[31][32][33]. In this work, we showed that retinal cells respond to SCM by an increase in cell survival and [ 3 H]-choline uptake.…”

Section: Discussionmentioning

confidence: 52%

“…IL-2 is an archetypal example of an immunoregulatory interleukin initially described to have only immunological functions. Nevertheless, the action of this cytokine on several neuronal subpopulations, such as cortical, hippocampal, cerebellar, striatal and septal neurons, has been shown [21,31,32]. IL-2 also stimulates cholinergic and dopaminergic neurons, modulating the release of acetylcholine, dopamine and catecholamines from specific brain regions [21,34,35].…”

Section: Discussionmentioning

confidence: 99%

Effect of Spleen-Cell-Conditioned Medium on [<sup>3</sup>H]-Choline Uptake by Retinal Cells in vitro Is Mediated by IL-2

Sholl‐Franco

Marques

Paes‐de‐Carvalho

et al. 2000

Neuroimmunomodulation

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Cytokines are essential molecules throughout the development of the nervous system and also play an important role during the adult life span. In the present work, we analyzed in vitro the effect of spleen-cell-conditioned medium (SCM) on the survival and [³H]-choline uptake of neonatal rat retinal cells. SCM induced an increase in neuronal survival, glial cell proliferation and neurite outgrowth, as evaluated by biochemical and morphological criteria. These effects were time dependent; after 120 h, SCM induced a 6-fold increase in the total protein level. The effect of SCM was blocked both by the inhibition of protein tyrosine kinase activity (10 μM genistein) and by the inhibition of cell division (20 μM fluorodeoxyuridine). SCM also increased the uptake of [³H]-choline by retinal cells. The effect was time dependent. The maximum effect was obtained after 48 h and was maintained at a high level until 120 h. Treatment by 10 μM genistein and 15 μM bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM) (an intracellular calcium chelator) completely blocked this effect. However, 20 μM fluorodeoxyuridine did not abolish it. Conditioned medium obtained from glial cells stimulated with SCM (S-GCM) induced an effect on [³H]-choline uptake earlier than that promoted by SCM. Anti-interleukin-2 (IL-2) antibodies blocked the effect of both SCM and S-GCM on [³H]-choline uptake after 48 and 72 h. IL-2 (50 U/ml) elicited the same effect as that observed when the cells were maintained in the presence of SCM. Taken together, our results suggest that IL-2 plays an important role in controlling the survival and differentiation of retinal cells in vitro.

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Interleukin‐2 as a neurotrophic factor for supporting the survival of neurons cultured from various regions of fetal rat brain

Cited by 72 publications

References 39 publications

Schizophrenia and cytokines

Schizophrenia and cytokines

Interleukin-2 and Its Effects in the Central Nervous System

Effect of Spleen-Cell-Conditioned Medium on [<sup>3</sup>H]-Choline Uptake by Retinal Cells in vitro Is Mediated by IL-2

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