Natale, Silvia (2018) Identification of the role played by Na+/Ca2+ exchanger 1 (NCX1) in hippocampal dependent anxiety, spatial learning and memory consolidation through genetic modified mice and newly synthesized compounds. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Identification of the role played by Na+/Ca2+ exchanger 1 (NCX1) in hippocampal dependent anxiety, spatial learning and memory consolidation through genetic modified mice and newly synthesized compounds. |
| Autori: | Autore Email Natale, Silvia silvia.natale@unina.it |
| Data: | 4 Dicembre 2018 |
| Numero di pagine: | 122 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Neuroscienze e Scienze Riproduttive ed Odontostomatologiche |
| Dottorato: | Neuroscienze |
| Ciclo di dottorato: | 31 |
| Coordinatore del Corso di dottorato: | nome email Taglialatela, Maurizio mtaglial@unina.it |
| Tutor: | nome email Molinaro, Pasquale [non definito] |
| Data: | 4 Dicembre 2018 |
| Numero di pagine: | 122 |
| Parole chiave: | memory; anxiety, pharmacology |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare Area 05 - Scienze biologiche > BIO/14 - Farmacologia Area 05 - Scienze biologiche > BIO/15 - Biologia farmaceutica |
| Depositato il: | 19 Dic 2018 11:18 |
| Ultima modifica: | 30 Giu 2020 08:47 |
| URI: | http://www.fedoa.unina.it/id/eprint/12468 |
Abstract
The Na+/Ca2+ exchanger 1 (NCX1), which is highly expressed in the hippocampus, cortex, and amygdala, regulates Akt1 phosphorylation. Since Akt1 is part of the PTEN/Akt1/CREB signaling pathway, which participates in synaptic plasticity and long-term memory, we investigated whether NCX1 expression/activity might also be involved in some hippocampal-dependent learning and memory processes. To test this hypothesis, we used two genetically-modified mice to selectively overexpress (NCX1.4over) or downregulate (NCX1ko) NCX1 in hippocampal, cortical, and amygdala neurons and a newly synthesized selective NCX1 stimulating compound, named CN-PYB2. Both NCX1.4over and CN-PYB2-treated mice showed increased phosphorylated CaMKII levels in the hippocampus and improved long-term spatial learning and memory performance. By contrast, NCX1ko mice displayed a decrease in both. In addition, both NCX1.4over and CN-PYB2-treated mice also displayed an increase in context-dependent anxiety. Altogether, these results demonstrate that neuronal NCX1 participates in hippocampal-amygdala memory consolidation and promote anxiety behavior.
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