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Archivio digitale delle tesi discusse presso l’Università di Pisa

Tesi etd-10042022-224937


Tipo di tesi
Tesi di laurea magistrale
Autore
SCORRANO, MANUEL
URN
etd-10042022-224937
Titolo
Effects of Systemic Lithium Administration on Neuronal Chloride Homeostasis and Cortical Electrophysiology
Dipartimento
BIOLOGIA
Corso di studi
NEUROSCIENCE
Relatori
relatore Prof. Ratto, Gian Michele
relatore Dott.ssa Landi, Silvia
Parole chiave
  • animal model
  • electrophysiology
  • imaging
  • lithium
Data inizio appello
25/10/2022
Consultabilità
Non consultabile
Data di rilascio
25/10/2025
Riassunto
Lithium salts have been for decades a first-line treatment for neuropsychiatric disorders, such us Bipolar Disorder (BD); furthermore, in the last few years lithium has been considered also a valuable candidate for treatment of traumatic brain injury and various neurodegenerative conditions. However, how this monocation could yield such profound therapeutic effects remains unclear. The therapeutic action of lithium is particularly complex and mainly related to its interaction with other cations, such us Na+ and Mg2+, in various signaling proteins and cofactors, promoting various effects on gene expression, neurotransmitter signaling, receptor-mediated signaling, signal transduction processes, circadian regulation and ion transport. In this study, starting from preliminary data of in vivo imaging of intracellular chloride concentration, we show that systemic administration of lithium lowers intracellular chloride concentration [Cl-]i in neocortical pyramidal cells. As a consequence, the lithium-mediated lowering of [Cl-]i could increase the strength of GABA-mediated inhibition on pyramidal neurons. Conversely, we show that lithium withdrawal causes a higher level of excitability and an increased susceptibility to epileptogenesis. Further experiments will be conducted in this direction to demonstrate whether and how lithium withdrawal causes an increase in [Cl-]i, possibly leading to a switch towards a depolarizing effect of GABA.
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