Cargando…
Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat
The loop diuretic bumetanide (Bumex) is thought to have antiepileptic properties via modulate GABA(A) mediated signaling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signaling, we sought to investigate wh...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219661/ https://www.ncbi.nlm.nih.gov/pubmed/25369049 http://dx.doi.org/10.1371/journal.pone.0106692 |
_version_ | 1782342613246935040 |
---|---|
author | Ko, Meng Chang Lee, Min Chong Amstislavskaya, Tamara G. Tikhonova, Maria A. Yang, Yi-Ling Lu, Kwok-Tung |
author_facet | Ko, Meng Chang Lee, Min Chong Amstislavskaya, Tamara G. Tikhonova, Maria A. Yang, Yi-Ling Lu, Kwok-Tung |
author_sort | Ko, Meng Chang |
collection | PubMed |
description | The loop diuretic bumetanide (Bumex) is thought to have antiepileptic properties via modulate GABA(A) mediated signaling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signaling, we sought to investigate whether they also affect hippocampal function. The current study was performed to evaluate the possible role of NKCC1 on the hippocampal function. Brain slice extracellular recording, inhibitory avoidance, and western blot were applied in this study. Results showed that hippocampal Long-term potentiation was attenuated by suprafusion of NKCC1 inhibitor bumetanide, in a dose dependent manner. Sequent experiment result showed that Intravenous injection of bumetanide (15.2 mg/kg) 30 min prior to the training session blocked inhibitory avoidance learning significantly. Subsequent control experiment's results excluded the possible non-specific effect of bumetanide on avoidance learning. We also found the phosphorylation of hippocampal MAPK was attenuated after bumetanide administration. These results suggested that hippocampal NKCC1 may via MAPK signaling cascade to possess its function. |
format | Online Article Text |
id | pubmed-4219661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42196612014-11-12 Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat Ko, Meng Chang Lee, Min Chong Amstislavskaya, Tamara G. Tikhonova, Maria A. Yang, Yi-Ling Lu, Kwok-Tung PLoS One Research Article The loop diuretic bumetanide (Bumex) is thought to have antiepileptic properties via modulate GABA(A) mediated signaling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signaling, we sought to investigate whether they also affect hippocampal function. The current study was performed to evaluate the possible role of NKCC1 on the hippocampal function. Brain slice extracellular recording, inhibitory avoidance, and western blot were applied in this study. Results showed that hippocampal Long-term potentiation was attenuated by suprafusion of NKCC1 inhibitor bumetanide, in a dose dependent manner. Sequent experiment result showed that Intravenous injection of bumetanide (15.2 mg/kg) 30 min prior to the training session blocked inhibitory avoidance learning significantly. Subsequent control experiment's results excluded the possible non-specific effect of bumetanide on avoidance learning. We also found the phosphorylation of hippocampal MAPK was attenuated after bumetanide administration. These results suggested that hippocampal NKCC1 may via MAPK signaling cascade to possess its function. Public Library of Science 2014-11-04 /pmc/articles/PMC4219661/ /pubmed/25369049 http://dx.doi.org/10.1371/journal.pone.0106692 Text en © 2014 Ko et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ko, Meng Chang Lee, Min Chong Amstislavskaya, Tamara G. Tikhonova, Maria A. Yang, Yi-Ling Lu, Kwok-Tung Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat |
title | Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat |
title_full | Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat |
title_fullStr | Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat |
title_full_unstemmed | Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat |
title_short | Inhibition of NKCC1 Attenuated Hippocampal LTP Formation and Inhibitory Avoidance in Rat |
title_sort | inhibition of nkcc1 attenuated hippocampal ltp formation and inhibitory avoidance in rat |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219661/ https://www.ncbi.nlm.nih.gov/pubmed/25369049 http://dx.doi.org/10.1371/journal.pone.0106692 |
work_keys_str_mv | AT komengchang inhibitionofnkcc1attenuatedhippocampalltpformationandinhibitoryavoidanceinrat AT leeminchong inhibitionofnkcc1attenuatedhippocampalltpformationandinhibitoryavoidanceinrat AT amstislavskayatamarag inhibitionofnkcc1attenuatedhippocampalltpformationandinhibitoryavoidanceinrat AT tikhonovamariaa inhibitionofnkcc1attenuatedhippocampalltpformationandinhibitoryavoidanceinrat AT yangyiling inhibitionofnkcc1attenuatedhippocampalltpformationandinhibitoryavoidanceinrat AT lukwoktung inhibitionofnkcc1attenuatedhippocampalltpformationandinhibitoryavoidanceinrat |