Franco, Cristina
(2015)
NaV1.6 as a new potential target of Alzheimer's Disease.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
NaV1.6 as a new potential target of Alzheimer's Disease |
| Autori: |
| Autore | Email |
|---|
| Franco, Cristina | francocristina2@virgilio.it |
|
| Data: |
Marzo 2015 |
| Numero di pagine: |
78 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Neuroscienze e Scienze Riproduttive ed Odontostomatologiche |
| Scuola di dottorato: |
Medicina molecolare |
| Dottorato: |
Neuroscienze |
| Ciclo di dottorato: |
27 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Annunziato, Lucio | [non definito] |
|
| Tutor: |
| nome | email |
|---|
| Pannaccione, Anna | [non definito] |
|
| Data: |
Marzo 2015 |
| Numero di pagine: |
78 |
| Parole chiave: |
NaV1.6, Alzheimer's Disease |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/14 - Farmacologia |
[error in script]
[error in script]
| Depositato il: |
16 Apr 2015 08:59 |
| Ultima modifica: |
16 Apr 2018 01:00 |
| URI: |
http://www.fedoa.unina.it/id/eprint/10545 |
| DOI: |
10.6093/UNINA/FEDOA/10545 |
Abstract
Alterations of the neuronal excitability and ionic homeostasis are becoming crucial events of Alzheimer's Disease (AD). The voltage-gated sodium (NaV) channels play an essential role in the control of the neuronal excitability. In fact, they trigger the generation and propagation of action potentials suggesting their involvement in AD. However, the NaV channel role has not yet been clarified in AD. The aim of the present study was to investigate the effects of Aβ1-42 peptide on NaV channels in a transgenic mouse model of AD, Tg2576. The Aβ1-42-exposure modulated selectively Nav1.6 channel expression and activity in primary hippocampal neurons. In particular, Aβ1-42-exposure induced a time-dependent modulation of NaV currents with a peak at 24 hrs accompanied by a significant leftward shift in the voltage dependence of activation. Interestingly, the NaV1.6 knockingdown completely counteracted the NaV current increase suggesting a possible NaV1.6 involvement in AD. Similar results were obtained in Tg2576 hippocampal neurons. The anisomycin, a well known selective NaV1.6 current inhibitor through an p38 MAPK activation, induced a significant reduction of the NaV current peak recorded in Tg2576 hippocampal neurons compared to that recorded in absence of anisomycin. Immunocytochemical analysis revealed that NaV1.6-immunoreactivity signal was higher in Tg2576 hippocampal neurons than in wild type whereas in the presence of anisomycin the NaV1.6 signal was lower. These results suggest that NaV1.6 channel hyperactivity could represent a new potential target in AD.
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