Proteomska analiza likvora u pasa s hernijacijom intervertebralnog diska

master's thesis

• Title (english): Proteomic analysis of cerebrospinal fluid in dogs with intervertebral disc herniation
• Author: Andrea Starčević
• Mentor: Ozren Smolec (mentor)
• Mentor: Anita Horvatić (mentor)
• Committee member: Josipa Kuleš (predsjednik povjerenstva)
• Committee member: Anita Horvatić (član povjerenstva)
• Committee member: Ozren Smolec (član povjerenstva)
• Granter: University of Zagreb; Faculty of Veterinary Medicine; Zagreb
• Defense date and country: 2023, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Veterinary Medicine; Veterinary Clinical Sciences

Abstract

Hernijacija intervertebralnog diska važna je i česta patologija kako u ljudi, tako i u pasa.
Iako je slikovna dijagnostika (CT i MR) glavna rutinska metoda dijagnoze IVDH, nemoguće
ju je primijeniti u otkrivanju ranog stadija bolesti, kao i objašnjavanju molekulskih procesa i
interakcija proteina koji sudjeluju u patofiziologiji bolesti. Upravo s tim ciljem, provedena je
kvalitativna i kvantitativna proteomska analiza likvora 6 zdravih pasa kao i 9 pasa s IVDH
temeljena na spektrometriji masa koristeći algoritam SEQUEST u sklopu računalog programa
Proteome Discoverer. Identificirano je 205 proteina likvora, od kojih je 75 jedinstvenih
proteina diferencijalno eksprimirano. Genska ontologija ukazala je da su dobiveni proteini koji
su uključeni u vezanje kalcija, oksidativni stres, metabolizam lipida, polimerizaciju kolagena,
upalne procese i imunološki odgovor. Identificirani su proteini s dijagnostičkim potencijalom
koji sudjeluju u neuropatskoj boli, mijelinizaciji, neuroinflamaciji i imunološkom odgovoru.
Njihova klinička primjena olakšala bi dijagnostiku IVHD u ranoj fazi bolesti. Jedan od
navedenih proteina, točnije paraoksonza 1 (PON1), koji ima ključnu ulogu u održavanju
homeostatske ravnoteže intervertebralnog diska, analitički je validiran, no za kliničku primjenu
u dijagnostici potrebna je validacija na većem broju pacijenata.

Abstract (english)

Intervertebral disc herniation is an important and common pathology in both humans
and dogs. Although imaging diagnostics (CT and MR) is the main routine method of
diagnosing IVDH, it can not be used to detect the early stage of the disease, as well as to explain
the molecular processes and protein interactions involved in the pathophysiology of the disease.
In this light, to decipher molecules involved in pathophysiology of IVDH, a qualitative and
quantitative proteomic analysis of the cerebrospinal fluid of 6 healthy dogs as well as 9 dogs
with IVDH was performed using mass spectrometry-based proteomics. Using the SEQUEST
algorithm integrated within Proteome Discoverer software, 205 cerebrospinal fluid proteins
were identified, 75 of which were differentially expressed. Gene ontology indicated that the
obtained proteins are involved in calcium binding, oxidative stress, lipid metabolism, collagen
polymerization, inflammatory processes and immune response. Proteins with diagnostic
potential involved in neuropathic pain, myelination, neuroinflammation and immune response
were identified herein. Their clinical application of those molecules would facilitate the
diagnosis of IVHD in the early stages of the disease. One of the differentially expressed
proteins, more precisely paraoxonase 1 (PON1), which plays a key role in maintaining the
homeostatic balance of the intervertebral disc, has been analytically validated, but for its
clinical application in IVDH diagnostics, validation on a larger number of patients is required.

• Keywords: IVDH; proteomika; likvor; pas; PON1
• Keywords (english): IVDH; proteomics; cerebrospinal fluid; dog; PON 1
• Language: croatian
• URN:NBN: urn:nbn:hr:178:896578
• Study programme: Title: Veterinary Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica veterinarske medicine (doktor/doktorica veterinarske medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-10-18 09:42:34