Title Optogenetika u animalnim modelima temporolimbičke epilepsije
Title (english) Optogenetics in animal models of temporolimbic epilepsy
Author Sanja Delovski
Mentor Mario Vukšić (mentor)
Committee member Goran Šimić (predsjednik povjerenstva)
Committee member Zdravko Petanjek (član povjerenstva)
Committee member Mario Vukšić (član povjerenstva)
Granter University of Zagreb School of Medicine (Department of Physiology and Immunology) Zagreb
Defense date and country 2019-07-12, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Basic Medical Sciences Human Physiology
Abstract Epilepsije su paroksizmalni poremećaji svijesti povezani sa sinkroniziranim, abnormalnim i spontanim izbijanjima koja se mogu pojaviti difuzno ili fokalno. Danas veliki problem predstavljaju farmakorezistentne, inoperabilne epilepsije, koje još uvijek obuhvaćaju znatan dio pacijenata. Najčešći je oblik fokalne epilepsije temporolimbička epilepsija. Epileptogeno žarište temporolimbičke epilepsije najčešće se povezuje s hipokampalnom sklerozom. Postoji više teorija nastanka epileptičnih napadaja, od gubitka GABA stimulacije, preko stimulacije perforantnog puta, do neadekvatne diferencijacije zrnatih stanica iz subgranularne zone, kao i uloge mahovinastih stanica, a posebno njihovog smanjenog broja nakon traumatske ozljede mozga. Stoga je razvijeno više vrsta animalnih modela na kojima se provode istraživanja u svrhu boljeg razumijevanja patofizioloških osnova epilepsije. Njihova važnost leži u činjenici da, zbog etičkih razloga, eksperimentalno izazivanje epileptičnih napadaja na ljudima u svrhu istraživanja novih antiepileptika nije dopušteno. Stoga je izrazito bitno razviti što vjerodostojniji životinjski model epilepsije na kojem bi se specifično istraživanje moglo provesti. Eksperimentalno se epilepsija može izazvati kemijski, sustavnom ili intrahipokampalnom primjenom tvari poput kainatne kiseline ili pilokarpina. Druga mogućnost je elektrofiziološka stimulacija glavnog puta koji iz entorinalne moždane kore vodi do hipokampusa, tzv. perforantnog puta. Budući da ni jedna od tih metoda nije u potpunosti selektivna, pojavila se potreba za novim pristupom. Optogenetika je metoda kojom se izvanjskom primjenom svjetlosti mogu po volji aktivirati ili inhibirati specifične živčane stanice, nakon eksperimentalnog umetanja voltažnih kanalnih receptora, opsina. Izborom vrste receptora koji će se eksprimirati na staničnoj membrani moguće je potaknuti ili zaustaviti epileptične napadaje, što je specifičnost te metode. Vremenska i prostorna specifičnost postiže se usklađenom primjenom svjetlosti putem optičke niti koja je implantirana u žarišno područje. Ukoliko je izvor svjetlosti, laser ili dioda, povezan s EEG uređajem koji bilježi električna izbijanja u pravom trenutku možemo zaustaviti inicirani napadaj. Zbog navedenih prednosti optogenetika će doprinijeti boljem razumijevanju neurobiološke podloge nastanka epileptičnih napadaja, kao i razvitku mogućih novih terapijskih pristupa.
Abstract (english) Epilepsy is a paroxysmal disturbance of consciousness associated with synchronized, abnormal and spontaneous seizures that may occur diffusely or focally. A major problem today is pharmacoresistant, inoperable epilepsy, which still affects a significant number of patients. The most common form of focal epilepsy is temporolimbic epilepsy. The epileptogenic focus of temporolimbic epilepsy is most often associated with hippocampal sclerosis. There are several theories of epileptic seizures which include the loss of GABA stimulation, the perforant pathway stimulation and the inadequate differentiation of granular cells from the subgranular zone, but also the role of mossy cells, especially their reduced number after traumatic brain injury. Therefore, several types of animal models have been developed to carry out studies for better understanding of the pathophysiological bases of epilepsy. Their importance lies in the fact that experimental induction of epileptic seizures on humans with the purpose of exploring new antiepileptics is not allowed because of ethical reasons. It is therefore essential to develop the most credible animal epileptic model on which specific research could be carried out. In experiments, epilepsy can be induced by chemicals, i.e. systemic or intrahippocampal application of substances such as kainic acid or pilocarpine. Another option is the electrophysiological stimulation of the main pathway leading from the entorhinal cerebral cortex to the hippocampus, i.e. the perforant pathway. Since none of these methods is completely selective, the need for a new approach appeared. Optogenetics is a method by which externally applied light can deliberately activate or inhibit specific neurons after experimental insertion of the receptor voltage channels, i.e. opsines. The specificity of this method lies in the fact that it is possible to induce or stop epileptic seizures by selecting a receptor type that will be expressed on the cell membrane. Time and space specificity are achieved by synchronized application of light by means of an optical fiber implanted into the focal area. If the light source, a laser or a diode, is connected to an EEG device that records electrical outbreaks we can stop an induced seizure at the right time. Because of the above mentioned advantages, optogenetics will contribute to better understanding of the neurobiological basis of epileptic seizures, as well as the development of potential new therapeutic approaches.
Keywords
temporolimbička epilepsija
mahovinaste stanice
animalni modeli
opsini
optogenetika
Keywords (english)
temporolimbic epilepsy
mossy cells
animal models
opsins
optogenetics
Language croatian
URN:NBN urn:nbn:hr:105:259113
Study programme Title: Medicine Study programme type: university Study level: integrated undergraduate and graduate Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resource Text
File origin Born digital
Access conditions Open access
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Created on 2020-01-07 13:22:17