The administration of the ryanodine receptor (RyR) agonist 4-Cmc (0.003–9 nmol per mouse intracerebroventricularly (i.c.v.) ameliorated memory functions, whereas the RyR antagonist ryanodine (0.0001–1 nmol per mouse i.c.v.) induced amnesia in the mouse passive avoidance test. The role of the type 1, 2, and 3 RyR isoforms in memory processes was then evaluated by inhibiting the expression of the three RyR proteins in the mouse brain. A selective knockdown of the RyR isoforms was obtained by the i.c.v. administration of antisense oligonucleotides (aODNs) complementary to the sequence of RyR1, RyR2 and RyR3 proteins, as demonstrated by immunoblotting experiments. RyR1 (5–9 nmol per mouse i.c.v.) knockdown mice did not show any memory dysfunction. Conversely, RyR2 (1–7 nmol per mouse i.c.v.) and RyR3 (1–7 nmol per mouse i.c.v.) knockdown animals showed an impairment of memory processes. This detrimental effect was temporary and reversible, disappearing 7 d after the end of the aODN treatment. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous mobility and inspection activity, as revealed by the hole-board test. In conclusion, the lack of any involvement of cerebral RyR1 was demonstrated. These findings also showed the involvement of type 2 and type 3 RyR in the modulation of memory functions identifying these cerebral RyR isoforms as critical targets underlying memory processes.

Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes / Nicoletta Galeotti; Alessandro Quattrone; Elisa Vivoli; Monica Norcini; Alessandro Bartolini; Carla Ghelardini. - In: LEARNING & MEMORY. - ISSN 1072-0502. - ELETTRONICO. - 15:(2008), pp. 315-323. [10.1101/lm.929008]

Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes.

GALEOTTI, NICOLETTA;BARTOLINI, ALESSANDRO;GHELARDINI, CARLA
2008

Abstract

The administration of the ryanodine receptor (RyR) agonist 4-Cmc (0.003–9 nmol per mouse intracerebroventricularly (i.c.v.) ameliorated memory functions, whereas the RyR antagonist ryanodine (0.0001–1 nmol per mouse i.c.v.) induced amnesia in the mouse passive avoidance test. The role of the type 1, 2, and 3 RyR isoforms in memory processes was then evaluated by inhibiting the expression of the three RyR proteins in the mouse brain. A selective knockdown of the RyR isoforms was obtained by the i.c.v. administration of antisense oligonucleotides (aODNs) complementary to the sequence of RyR1, RyR2 and RyR3 proteins, as demonstrated by immunoblotting experiments. RyR1 (5–9 nmol per mouse i.c.v.) knockdown mice did not show any memory dysfunction. Conversely, RyR2 (1–7 nmol per mouse i.c.v.) and RyR3 (1–7 nmol per mouse i.c.v.) knockdown animals showed an impairment of memory processes. This detrimental effect was temporary and reversible, disappearing 7 d after the end of the aODN treatment. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous mobility and inspection activity, as revealed by the hole-board test. In conclusion, the lack of any involvement of cerebral RyR1 was demonstrated. These findings also showed the involvement of type 2 and type 3 RyR in the modulation of memory functions identifying these cerebral RyR isoforms as critical targets underlying memory processes.
2008
15
315
323
Nicoletta Galeotti; Alessandro Quattrone; Elisa Vivoli; Monica Norcini; Alessandro Bartolini; Carla Ghelardini
File in questo prodotto:
File Dimensione Formato  
articolo n. 3.pdf

accesso aperto

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Open Access
Dimensione 573.84 kB
Formato Adobe PDF
573.84 kB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/326918
Citazioni
  • ???jsp.display-item.citation.pmc??? 26
  • Scopus 54
  • ???jsp.display-item.citation.isi??? 55
social impact