Morphological analysis of the dendritic tree and the expression and localization of actin-modulating protein synaptopodin in hippocampal granule cells of TNF-α KO mice

doctoral thesis

• Title (croatian): Morfološka analiza dendritičkog stabla te izražaj i lokalizacija aktin-modulirajućeg proteina synaptopodina u hipokampalnim zrnatim stanicama TNF-α-KO miševa.
• Author: Dinko Smilović
• Mentor: Mario Vukšić (mentor)
• Committee member: Zdravko Petanjek (predsjednik povjerenstva)
• Committee member: Goran Šimić (član povjerenstva)
• Committee member: Ivica Kostović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2021-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Changes in the morphology of dendrites and dendritic spines are tightly correlated to the functional properties of neurons. The underlying mechanisms are under strict control by multiple effectors. One of such proteins, the tumor necrosis factor α (TNF-α) has been shown to influence synaptic transmission and plasticity and is tightly connected to the actin-modulating protein synaptopodin (SP). We performed a detailed analysis of dendritic arbors and dendritic spines of dentate granule cells in mice mutants lacking TNF-α or its receptors. Fixed hippocampal sections were double-stained for SP, a molecular marker for strong and stable spines. We have shown that granule cells of TNF-deficient mice have fewer deficits in dendritic tree arborization after denervation. Dendritic spine density was reduced by 20% in these mice, and a compensatory increase in the size of large, SP+ spines was seen. A strikingly similar pattern of changes was seen in mice lacking TNF-R1, but not in mice lacking TNF-R2, showcasing that TNF-R1 is the dominant effector for this mechanism. Genetic removal of both receptors caused a large, 28% reduction in average spine sizes, and the compensatory, homeostatic increase of large spine sizes and SP content was absent.

Abstract (croatian)

Promjene u morfologiji dendrita i dendritičkih trnova usko su povezane s funkcionalnim svojstvima neurona. Osnovni mehanizmi tih promjena su pod strogom kontrolom mnogih molekula. Pokazalo se da jedan od takvih proteina, faktor tumorske nekroze α (TNF-α) utječe na sinaptički prijenos i plastičnost te je usko povezan s aktin-modulirajućim proteinom synaptopodinom (SP). U ovom radu smo detaljno analizirali dendritičko stablo i dendritičke trnove zrnatih stanica girusa dentatusa u miševa mutanata kojima nedostaje gen za TNF-α ili njegovi receptori. Fiksirane hipokampalne kriške su bile imunohistokemijski obojene za SP, molekularni marker stabilnih i snažnih dendritičkih trnova. Pokazali smo da zrnate stanice miševa kojima nedostaje gen za TNF-α imaju manje promjena u grananju dendritičkog stabla nakon denervacije. Gustoća dendritičkih trnova je smanjena za 20% kod tih miševa, a uočen je nadomjesni porast veličine velikih SP+ dendritičkih trnova. Zapanjujuće, sličan obrazac promjena viđen je kod miševa kojima nedostaje gen za TNF-R1, ali ne i kod miševa kojima nedostaje gen za TNF-R2, ukazujući na to da je TNF-R1 odlučujući čimbenik u nastanku ovih promjena. Genetsko uklanjanje oba receptora prouzročilo je veliko, 28% smanjenje prosječnih veličina dendritičkih trnova, te je u tim miševima izostao kompenzacijski, homeostatski porast velikih dendritičkih trnova, kao i sadržaja SP.

• Keywords: morphological analysis; dendritic tree; protein synaptopodin
• Keywords (croatian): morfološka analiza; dendritičko stablo; protein sinaptopodin
• Language: english
• URN:NBN: urn:nbn:hr:105:524607
• Promotion: 2021
• Project: Number: KK.01.1.1.01.0007; Title: Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi; Leader: Ivica Kostović; Jurisdiction: Croatia; Funder: EK
• Study programme: Title: Neuroscience; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 115 str.
• File origin: Born digital
• Access conditions: Open access
• Public note: Sumentor: Thomas Deller
• Created on: 2021-08-03 07:19:13