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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-02152021-181542


Thesis type
Tesi di laurea magistrale
Author
MASINI, GRETA
URN
etd-02152021-181542
Thesis title
Injection of extracellular vesicles carrying β-amyloid in the Lateral Entorhinal Cortex induces progressive memory deficits
Department
BIOLOGIA
Course of study
NEUROSCIENCE
Supervisors
relatore Prof. Origlia, Nicola
Keywords
  • Alzheimer
  • Entorhinal Cortex
  • Hippocampus
  • Memory
  • microglia
  • vesicles
Graduation session start date
23/03/2021
Availability
Full
Summary
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and cognitive deficit. Extensive literature implicates propagation of synaptic dysfunction along the Entorhinal-Hippocampal connections as an early event in AD models. However, the mechanisms by which this propagation occurs are not entirely clear. We propose microglia-derived Extracellular Vesicles (EVs) as possible carriers of pathogenic proteins, including Aβ, over large distances, leading to progression of synaptic dysfunction between connected regions. Previous experiments also demonstrated that Aβ-EVs, stereotaxically injected into Lateral Entorhinal Cortex (LEC), was able to inhibit LTP, firstly in the vicinity of injection site and then propagates to Hippocampus, the main target of EC. These effects were inhibited by Annexin V, blocking EVS motion. The aim of the present work was to investigate whether the spreading of synaptic dysfunction corresponds to progressive memory impairments using behavioural tasks that differently involve non-associative hippocampal dependent task (ORT) and LEC–dependent associative tasks (OPRT and OPCRT). Mice (male C57bl/6J, 3/4 months of age) were injected in the LEC with different treatments: i) Aβ-EVs, ii) synthetic Aβ [1-42], iii) ctrl-EVs, iv) Aβ-EVs + Annexin V, v) vehicle. After injection mice behaviour was evaluated at different time points. The behavioural analysis revealed that 1h after the injection of Aβ-EVs, the memory impairment was restricted to LEC-dependent tasks (OPCRT), but after 24 h only the Aβ-EVs group showed a memory impairment also in the non-associative task, suggesting that EVs contribute significantly to the propagation of memory dysfunction to the hippocampus. The propagation of the effect was mitigated by pre-treating Aβ-EVs with Annexin V.
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