Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus

Ketogenic diet, a high fat and low carbohydrate diet, has been used as a non-pharmacological treatment in refractory epilepsy since 1920. In recent years, it has demonstrated to be effective in the treatment of numerous neurological and non-neurological diseases. Some neurological and neuropsychiatr...

Full description

Bibliographic Details
Main Authors: Leticia Granados-Rojas, Karina Jerónimo-Cruz, Tarsila Elizabeth Juárez-Zepeda, Miguel Tapia-Rodríguez, Armando R. Tovar, Rodolfo Rodríguez-Jurado, Liliana Carmona-Aparicio, Noemí Cárdenas-Rodríguez, Elvia Coballase-Urrutia, Matilde Ruíz-García, Pilar Durán
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-07-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnins.2020.00673/full
_version_ 1818958546706890752
author Leticia Granados-Rojas
Karina Jerónimo-Cruz
Tarsila Elizabeth Juárez-Zepeda
Miguel Tapia-Rodríguez
Armando R. Tovar
Rodolfo Rodríguez-Jurado
Liliana Carmona-Aparicio
Noemí Cárdenas-Rodríguez
Elvia Coballase-Urrutia
Matilde Ruíz-García
Pilar Durán
author_facet Leticia Granados-Rojas
Karina Jerónimo-Cruz
Tarsila Elizabeth Juárez-Zepeda
Miguel Tapia-Rodríguez
Armando R. Tovar
Rodolfo Rodríguez-Jurado
Liliana Carmona-Aparicio
Noemí Cárdenas-Rodríguez
Elvia Coballase-Urrutia
Matilde Ruíz-García
Pilar Durán
author_sort Leticia Granados-Rojas
collection DOAJ
description Ketogenic diet, a high fat and low carbohydrate diet, has been used as a non-pharmacological treatment in refractory epilepsy since 1920. In recent years, it has demonstrated to be effective in the treatment of numerous neurological and non-neurological diseases. Some neurological and neuropsychiatric disorders are known to be caused by gamma-aminobutyric acid (GABA)-mediated neurotransmission dysfunction. The strength and polarity of GABA-mediated neurotransmission are determined by the intracellular chloride concentration, which in turn is regulated by cation-chloride cotransporters NKCC1 and KCC2. Currently, it is unknown if the effect of ketogenic diet is due to the modulation of these cotransporters. Thus, we analyzed the effect of a ketogenic diet on the cation-chloride cotransporters expression in the dentate gyrus. We estimated the total number of NKCC1 immunoreactive (NKCC1-IR) neuronal and glial cells by stereology and determined KCC2 labeling intensity by densitometry in the molecular and granule layers as well as in the hilus of dentate gyrus of rats fed with normal or ketogenic diet for 3 months. The results indicated that ketogenic diet provided during 3 months increased KCC2 expression, but not NKCC1 in the dentate gyrus of the rat. The significant increase of KCC2 expression could explain, at least in part, the beneficial effect of ketogenic diet in the diseases where the GABAergic system is altered by increasing its inhibitory efficiency.
first_indexed 2024-12-20T11:27:28Z
format Article
id doaj.art-63e79cf4130443a0bb8e9147cc4e93f4
institution Directory Open Access Journal
issn 1662-453X
language English
last_indexed 2024-12-20T11:27:28Z
publishDate 2020-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neuroscience
spelling doaj.art-63e79cf4130443a0bb8e9147cc4e93f42022-12-21T19:42:20ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-07-011410.3389/fnins.2020.00673473516Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate GyrusLeticia Granados-Rojas0Karina Jerónimo-Cruz1Tarsila Elizabeth Juárez-Zepeda2Miguel Tapia-Rodríguez3Armando R. Tovar4Rodolfo Rodríguez-Jurado5Liliana Carmona-Aparicio6Noemí Cárdenas-Rodríguez7Elvia Coballase-Urrutia8Matilde Ruíz-García9Pilar Durán10Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Mexico City, MexicoLaboratorio de Neurociencias, Instituto Nacional de Pediatría, Mexico City, MexicoLaboratorio de Neurociencias, Instituto Nacional de Pediatría, Mexico City, MexicoUnidad de Microscopía, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, MexicoDepartamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartamento de Anatomía Patológica, Instituto Nacional de Pediatría, Mexico City, MexicoLaboratorio de Neurociencias, Instituto Nacional de Pediatría, Mexico City, MexicoLaboratorio de Neurociencias, Instituto Nacional de Pediatría, Mexico City, MexicoLaboratorio de Neurociencias, Instituto Nacional de Pediatría, Mexico City, MexicoServicio de Neurología, Instituto Nacional de Pediatría, Mexico City, MexicoLaboratorio de Biología Animal Experimental, Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, MexicoKetogenic diet, a high fat and low carbohydrate diet, has been used as a non-pharmacological treatment in refractory epilepsy since 1920. In recent years, it has demonstrated to be effective in the treatment of numerous neurological and non-neurological diseases. Some neurological and neuropsychiatric disorders are known to be caused by gamma-aminobutyric acid (GABA)-mediated neurotransmission dysfunction. The strength and polarity of GABA-mediated neurotransmission are determined by the intracellular chloride concentration, which in turn is regulated by cation-chloride cotransporters NKCC1 and KCC2. Currently, it is unknown if the effect of ketogenic diet is due to the modulation of these cotransporters. Thus, we analyzed the effect of a ketogenic diet on the cation-chloride cotransporters expression in the dentate gyrus. We estimated the total number of NKCC1 immunoreactive (NKCC1-IR) neuronal and glial cells by stereology and determined KCC2 labeling intensity by densitometry in the molecular and granule layers as well as in the hilus of dentate gyrus of rats fed with normal or ketogenic diet for 3 months. The results indicated that ketogenic diet provided during 3 months increased KCC2 expression, but not NKCC1 in the dentate gyrus of the rat. The significant increase of KCC2 expression could explain, at least in part, the beneficial effect of ketogenic diet in the diseases where the GABAergic system is altered by increasing its inhibitory efficiency.https://www.frontiersin.org/article/10.3389/fnins.2020.00673/fullketogenic dietNKCC1KCC2dentate gyrusoptical fractionatoroptical density
spellingShingle Leticia Granados-Rojas
Karina Jerónimo-Cruz
Tarsila Elizabeth Juárez-Zepeda
Miguel Tapia-Rodríguez
Armando R. Tovar
Rodolfo Rodríguez-Jurado
Liliana Carmona-Aparicio
Noemí Cárdenas-Rodríguez
Elvia Coballase-Urrutia
Matilde Ruíz-García
Pilar Durán
Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus
Frontiers in Neuroscience
ketogenic diet
NKCC1
KCC2
dentate gyrus
optical fractionator
optical density
title Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus
title_full Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus
title_fullStr Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus
title_full_unstemmed Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus
title_short Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus
title_sort ketogenic diet provided during three months increases kcc2 expression but not nkcc1 in the rat dentate gyrus
topic ketogenic diet
NKCC1
KCC2
dentate gyrus
optical fractionator
optical density
url https://www.frontiersin.org/article/10.3389/fnins.2020.00673/full
work_keys_str_mv AT leticiagranadosrojas ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT karinajeronimocruz ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT tarsilaelizabethjuarezzepeda ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT migueltapiarodriguez ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT armandortovar ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT rodolforodriguezjurado ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT lilianacarmonaaparicio ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT noemicardenasrodriguez ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT elviacoballaseurrutia ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT matilderuizgarcia ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus
AT pilarduran ketogenicdietprovidedduringthreemonthsincreaseskcc2expressionbutnotnkcc1intheratdentategyrus