Funkcionalne i biohemijske promene centralnog nervnog sistema u eksperimentalnom modelu hroničnog pelvičnog bola
Functional and biochemical alterations in central nervous system in an experimental model of chronic pelvic pain
Докторанд
Šutulović, NikolaМентор
Hrnčić, DraganЧланови комисије
Šuvakov, SonjaStanojlović, Olivera
Simić, Tatjana
Rašić-Marković, Aleksandra
Метаподаци
Приказ свих података о дисертацијиСажетак
Hronični prostatitis/sindrom hroničnog pelvičnog bola (CP/CPPS) je često udružen,
nerazjašnjenim mehanizmima, sa poremećajima centralnog nervnog sistema (CNS).
Ciljevi ove studije su bili utvrđivanje funkcionalnih i biohemijskih promena koje nastaju u
CNS kao posledica CP/CPPS, kao i ispitivanje potencijalnih mehanizama koji dovode do tih
promena.
Funkcionalno su ispitani podložnost za razvoj konvulzija, prag nocicepcije, ponašanje
povezano sa anksioznošću i depresijom i kognitivne sposobnosti. Biohemijskim ispitivanjem
obuhvaćeni su parametri redoks statusa i nivo proinflamatornih citokina i ICAM-1 u
strukturama mozga, kao i nivo testosterona i kortikosterona u serumu. Imunohistohemijski je
ispitan proces neurogeneze i gliogeneze u hipokampusu. Ispitivani su i potencijalni terapijski
efekti modulacije nivoa gasotransmitera CO i hronične aerobne fizičke aktivnosti u ovom
modelu.
Životinje sa eksperimentalnim CP/CPPS su razvile hiperekscitabilnost CNS, ali su povećano
ispoljavale ponas...anje povezano sa anksioznos ću i depresijom, kao i kognitivnu disfunkciju. U
hipokampusu, talamusu i korteksu zivotinja sa CP/CPPS doslo je do pojave oksidativnog stresa,
a nivo proinflamatornih citokina IL-β i IL-6 i ekspresija ICAM-1 bili su povećani u talamusu i
korteksu, sto ukazuje na neuroinflamaciju. Razvoj CP/CPPS je doveo do hormonskog disbalansa,
u vidu povećanja kortikosterona i smanjenja testosterona u serumu. Adultna neurogeneza je
bila smanjenog, a gliogeneza povećanog obima u hipokampusu, gde je utvrđen i smanjen broj
inhibitornih interneurona. Hronicni aerobni trening i CORM A1, donor CO, imali su
antinociptivno, anksiolitic ko, antidepresivno, antiinflamatorno i antikonvulzivno dejstvo u
modelu CP/CPPS, sto ukazuje na njihove potencijalne terapijske efekte.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is often associated with
central nervous system (CNS) disorders by unelucidated mechanisms.
The aims of this study were to determine the functional and biochemical changes in the CNS
induced by CP/CPPS, as well as the potential underlying mechanisms.
Functional study included assessment of seizure susceptibility, nociception threshold,
anxiety- and depression-like behavior, and cognition. The biochemical analyses consisted of
assessment of redox status parameters, pro-inflammatory cytokines, and ICAM-1 expression in
the brain structures, and the concentration of testosterone and corticosterone in the serum.
The process of hippocampal neurogenesis and gliogenesis were examined
immunohistochemically. The potential therapeutic effects of the CO gasotransmitter level
modulation and chronic aerobic physical activity in this model were also investigated.
Animals with experimental CP/CPPS developed CNS hyperexcitability, increased anx...iety-
and depression-like behavior, as well as cognitive impairment. Oxidative stress occurred in the
hippocampus, thalamus, and cortex of animals with CP/CPPS, and the level of proinflammatory
cytokines IL-β and IL-6, and ICAM-1 expression were increased in the thalamus and cortex,
indicating neuroinflammation. Hormonal imbalance, as an increase in corticosterone and a
decrease in serum testosterone concentration, was observed. Adult neurogenesis was reduced,
while gliogenesis was increased in the hippocampus, and the lower number of hippocampal
inhibitory interneurons was also found. Chronic aerobic training and CORM A1 (CO releasing
molecule) had antinociceptive, anxiolytic, antidepressant, anti-inflammatory and
anticonvulsant effects in the CP/CPPS model, indicating their potential therapeutic effects.