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Tesi etd-02202020-022629


Thesis type
Tesi di laurea magistrale LM6
Author
SANTUCCI, FILIPPO
URN
etd-02202020-022629
Title
SG2 compound, synthetic T1AM analogue, exerts neuroprotective properties on a mouse model of Alzheimer's disease
Struttura
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Corso di studi
MEDICINA E CHIRURGIA
Supervisors
relatore Prof. Zucchi, Riccardo
correlatore Prof. Origlia, Nicola
Parole chiave
  • taar1
  • trace amine associated receptor 1
  • entorhinal cortex
  • ltp
  • long term potentiation
  • thyroid
  • Alzheimer's disease
  • thyronamine
Data inizio appello
10/03/2020;
Consultabilità
Secretata d'ufficio
Data di rilascio
10/03/2090
Riassunto analitico
In this study we used an Alzheimer Disease (AD) transgenic mouse model, hyperexpressing alleles of human APP gene linked to familial AD. Such mice accumulates Aβ, beginning from EC which then leads to progressive neurodegeneration. Impairment of EC synaptic plasticity is an early sign of neuronal degeneration in mhAPP, that can be evidenced as a loss of Long Term Potentiation (LTP) expression.

Previous experiments showed that mhAPP slices, perfused with ACSF enriched with 3-Iodothyronamine (T1AM) 5μM, regained LTP capacity after High Frequency Stimulation induction protocol (HFS). Since SG2 is a synthetic analogue of T1AM, we hypothesized that it may have a similar effect, and we decided to administer this compound in perfusion medium at different concentration.

In agreement with previous evidences, LTP cannot be elicited by HFS in mhAPP slices perfused with ACSF alone. We then tried to rescue LTP in mhAPP slices using the SG2 compound; however at the lowest concentration (1µM), 10 min perfusion of SG2 was not effective and the mean amplitude after HFS, was not significantly different from that of mhAPP exposed to ACSF alone (0.87 ± 0.06, n=7, versus 0.93 ± 0.044, n=9 ). In contrast, an higher concentration of SG2 (5 μM), recovered a LTP expression in mhAPP slices after HFS (1.14 ± 0.02, n=6), that was significantly higher than that in mhAPP slices alone (p=0.042), and in mhAPP slices perfused with SG2 1 μM (p=0.014).
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