Involvement of purinergic signaling components in selected structures of the forebrain of rats suffering from experimental autoimmune encephalomyelitis

Dokmanović, Tamara (author), Kreft, Marko (mentor), Dragić, Milorad (comentor)

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) accompanied by demyelination and subsequent neuronal damage that leads to permanent disability in young adults. The most commonly used experimental model for studying MS is experimental autoimmune encephalomyelitis (EAE), which exhibits main pathological features of the human disease. EAE is considered an inflammatory disease, and the neuroinflammation caused by EAE is tightly regulated by purinergic signaling. Various pathological events lead to neuronal damage, triggering release of large amounts of ATP, which then acts differently on purinoreceptors. Furthermore, exogenous ATP is removed by cascade hydrolysis by the action of the ectonucleotidase enzyme chain. The last step in ATP degradation is the dephosphorylation of AMP into adenosine by the action of ecto-5'-nucleotidase (eN/CD73). In this paper, we compare the expression levels of purinoreceptors A1R, A2AR, A2BR, and A3R, and the activity of purinergic enzymes, ecto-5'-nucleotidase, adenosine deaminase (ADA), AMPase and ADPase in selected brain regions of healthy control animals and animals in the peak of EAE, aiming to better understand the role of purinergic signaling in the pathophysiology of MS.

• Language: English
• Keywords: multiple sclerosis, experimental autoimmune encephalomyelitis, eN/CD73, adenosine receptors, adenosine deaminase, AMPase, ADPase
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Publisher: [T. Dokmanović]
• Year: 2024
• PID: 20.500.12556/RUL-163672
• UDC: 616.831(043.2)
• COBISS.SI-ID: 211959811
• Publication date in RUL: 10.10.2024

Secondary language

• Language: Slovenian
• Title: Vloga purinskih signalnih komponent v izbranih strukturah prednjih možganov podgan obolelih z eksperimentalnim avtoimunskim encefalomielitisom

Abstract

Multipla skleroza (MS) je kronična avtoimunska bolezen osrednjega živčnega sistema (CNS), ki jo spremlja demielinizacija in posledična poškodba nevronov, ki vodi do trajne invalidnosti pri mladih odraslih. Najpogosteje uporabljen eksperimentalni model za preučevanje MS je eksperimentalni avtoimunski encefalomielitis (EAE), ki kaže glavne patološke značilnosti človeške bolezni. EAE velja za vnetno bolezen in vnetje živčevja, ki ga povzroča EAE, je natančno regulirano s purinergičnim signaliziranjem. Različna patološka dogajanja vodijo do poškodb nevronov, sprožijo sproščanje velikih količin ATP, ki nato drugače deluje na purinoreceptorje. Poleg tega se eksogeni ATP odstranja s kaskadno hidrolizo z delovanjem encimske verige ektonukleotidaze. Zadnji korak v razgradnji ATP je defosforilacija AMP v adenozin z delovanjem ekto-5'- nukleotidaze (eN/CD73). V tem prispevku primerjamo nivoje izražanja purinergičnih receptorjev A1R, A2AR, A2BR in A3R ter aktivnost purinergičnih encimov, ekto-5'- nukleotidaze, adenozin deaminaze (ADA), AMPaze in ADPaze v izbranih predelih možganov zdravih kontrolnih živali in živali na vrhuncu EAE, da bi bolje razumeli vlogo purinergičnega signaliziranja v patofiziologiji MS.

• Keywords: multipla skleroza, eksperimentaalni avtoimunski encefalomielitis, eN/CD73, adenozinski receptorji, adenozin deaminaza, AMPaza, ADPaza