ETD

Archivio digitale delle tesi discusse presso l'Università di Pisa

Tesi etd-09202022-141237


Tipo di tesi
Tesi di dottorato di ricerca
Autore
NAZZI, SERENA
URN
etd-09202022-141237
Titolo
Impact of fluoxetine-induced change of 5-HT homeostasis on behavior and serotonergic innervation: identification of sensitive periods of plasticity and irreversible developmental critical windows
Settore scientifico disciplinare
BIO/06
Corso di studi
BIOLOGIA
Relatori
tutor Prof. Pasqualetti, Massimo
Parole chiave
  • development
  • plasticity
  • behavioral paradox
  • hippocampus
  • fluoxetine
  • Serotonergic fiber
Data inizio appello
23/09/2022
Consultabilità
Non consultabile
Data di rilascio
23/09/2025
Riassunto
The serotonergic system shows a high structural plasticity in response to the genetically induced abrogation of 5-HT. Here, using confocal imaging and 3D modeling analysis we first studied whether the serotonergic system responds to 5-HT fluctuations within the peri-physiological range that may occur throughout an individual’s adult life. Subsequently, we investigated on the effects of these 5-HT oscillations during pre- and early post-natal developmental period.
In the first study, chronically treating adult Tph2GFP knock-in mice with fluoxetine and subsequently suspending the treatment, we show that fluoxetine causes a reversible effect on mice behavior and also causes a reversible reduction in serotonergic fiber density in the hippocampus.
Then we mimic the human fluoxetine intake by treating Tph2GFP female mice throughout the gestation and lactation period until weaning. We investigate the effect of this treatment on adult offspring, demonstrating an increase in anxiety- and depressive-like behavior that confirm the “behavioral paradox” reported in literature. Then we analyze the serotonergic wiring in the offspring hippocampus during post-natal development up to adulthood and aging, showing that fluoxetine treatment affects irreversibly the morphology of 5-HT fibers by reducing the fiber density.
Overall, these data show that a change in 5-HT homeostasis that occurs when the nervous system is already formed (adulthood) causes reversible alterations to the serotonergic wiring, whereas if this oscillation occurs during development it irreversibly impacts the serotonergic circuitry and behavior.
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