Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats

Makoto Mizuno, Kiyofumi Yamada, Ana Olariu, Hiroyuki Nawa, Toshitaka Nabeshima

Research output: Contribution to journalArticle

402 Citations (Scopus)

Abstract

Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These resuits suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

Original languageEnglish
Pages (from-to)7116-7121
Number of pages6
JournalJournal of Neuroscience
Volume20
Issue number18
Publication statusPublished - 15-09-2000

Fingerprint

Brain-Derived Neurotrophic Factor
Maintenance
Oligonucleotides
Messenger RNA
Short-Term Memory
Hippocampus
Spatial Memory
Intraventricular Infusions
Neuronal Plasticity
Long-Term Potentiation
Antisense Oligonucleotides
Nerve Growth Factors
Frontal Lobe
Therapeutics
Locomotion
Nitric Oxide Synthase
Body Weight
Learning
Food

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

@article{420f9bac8bda49da97e939f10a8f0a5f,
title = "Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats",
abstract = "Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These resuits suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.",
author = "Makoto Mizuno and Kiyofumi Yamada and Ana Olariu and Hiroyuki Nawa and Toshitaka Nabeshima",
year = "2000",
month = "9",
day = "15",
language = "English",
volume = "20",
pages = "7116--7121",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "18",

}

Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. / Mizuno, Makoto; Yamada, Kiyofumi; Olariu, Ana; Nawa, Hiroyuki; Nabeshima, Toshitaka.

In: Journal of Neuroscience, Vol. 20, No. 18, 15.09.2000, p. 7116-7121.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats

AU - Mizuno, Makoto

AU - Yamada, Kiyofumi

AU - Olariu, Ana

AU - Nawa, Hiroyuki

AU - Nabeshima, Toshitaka

PY - 2000/9/15

Y1 - 2000/9/15

N2 - Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These resuits suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

AB - Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These resuits suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

UR - http://www.scopus.com/inward/record.url?scp=0034666119&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034666119&partnerID=8YFLogxK

M3 - Article

C2 - 10995859

AN - SCOPUS:0034666119

VL - 20

SP - 7116

EP - 7121

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 18

ER -