Memantine treatment reduces the expression of the K+/Cl- cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABAA receptor activation in mice

Gemma Molinaro, Giuseppe Battaglia, Barbara Riozzi, Luisa Di Menna, Liborio Rampello, Valeria Bruno, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K+/Cl- co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl- concentrations, which drive Cl- influx in response to GABAA receptor activation, we monitored the behavioural response to the GABAA receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABAA receptors that might contribute to the therapeutic and/or toxic effects of the drug.

Original languageEnglish
Pages (from-to)75-79
Number of pages5
JournalBrain Research
Volume1265
DOIs
Publication statusPublished - Apr 10 2009

Fingerprint

Memantine
GABA-A Receptors
Cerebral Cortex
Hippocampus
Diazepam
Rotarod Performance Test
Symporters
Poisons
Brain-Derived Neurotrophic Factor
Pharmaceutical Preparations
Alzheimer Disease
Neurons
potassium-chloride symporters

Keywords

  • BDNF
  • Diazepam
  • GABA receptor
  • KCC2
  • Memantine
  • Rotarod test

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

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abstract = "A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K+/Cl- co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl- concentrations, which drive Cl- influx in response to GABAA receptor activation, we monitored the behavioural response to the GABAA receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABAA receptors that might contribute to the therapeutic and/or toxic effects of the drug.",
keywords = "BDNF, Diazepam, GABA receptor, KCC2, Memantine, Rotarod test",
author = "Gemma Molinaro and Giuseppe Battaglia and Barbara Riozzi and {Di Menna}, Luisa and Liborio Rampello and Valeria Bruno and Ferdinando Nicoletti",
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AU - Molinaro, Gemma

AU - Battaglia, Giuseppe

AU - Riozzi, Barbara

AU - Di Menna, Luisa

AU - Rampello, Liborio

AU - Bruno, Valeria

AU - Nicoletti, Ferdinando

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N2 - A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K+/Cl- co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl- concentrations, which drive Cl- influx in response to GABAA receptor activation, we monitored the behavioural response to the GABAA receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABAA receptors that might contribute to the therapeutic and/or toxic effects of the drug.

AB - A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K+/Cl- co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl- concentrations, which drive Cl- influx in response to GABAA receptor activation, we monitored the behavioural response to the GABAA receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABAA receptors that might contribute to the therapeutic and/or toxic effects of the drug.

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