Effects of neonatal dexamethasone treatment on hippocampal synaptic function

Hsiao Ju Lin, Chiung Chun Huang, Kuei-Sen Hsu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objective: Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Surprisingly, little is known about the long-term neurodevelopmental outcomes of this therapy. Methods: Using a schedule of tapering doses of DEX similar to that used in premature infants, we examined the consequences of neonatal DEX treatment on hippocampal synaptic plasticity of infants and associative memory later in their lives. Results: Neonatal DEX treatment changed the direction of synaptic plasticity, favoring low-frequency, stimulation-induced, long-term depression and opposing the induction of long-term potentiation by high-frequency stimulation in adolescent (5-week-old) rats, but these alterations disappeared in young adult (8-week-old) rats. The effects of DEX on long-term depression and long-term potentiation were found to correlate with an increase in the autophosphorylation of Ca2+/ calmodulin-dependent protein kinase II and a decrease in the protein phosphatase 1 activity. Neonatal DEX treatment also disrupted memory retention in 5-week-old (but not 8-week-old) rats subjected to passive avoidance learning tasks. Interpretation: These results suggest that neonatal DEX treatment alters hippocampal synaptic plasticity and contextual fear memory formation in later life, but these impairments apparently are not permanent.

Original languageEnglish
Pages (from-to)939-951
Number of pages13
JournalAnnals of Neurology
Volume59
Issue number6
DOIs
Publication statusPublished - 2006 Jun 1

Fingerprint

Dexamethasone
Neuronal Plasticity
Long-Term Potentiation
Premature Infants
Therapeutics
Depression
Avoidance Learning
Protein Phosphatase 1
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Glucocorticoids
Lung Diseases
Fear
Young Adult
Appointments and Schedules
Chronic Disease
Morbidity

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Lin, Hsiao Ju ; Huang, Chiung Chun ; Hsu, Kuei-Sen. / Effects of neonatal dexamethasone treatment on hippocampal synaptic function. In: Annals of Neurology. 2006 ; Vol. 59, No. 6. pp. 939-951.
@article{b5b241fa823a4c0390cada75bd41aa08,
title = "Effects of neonatal dexamethasone treatment on hippocampal synaptic function",
abstract = "Objective: Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Surprisingly, little is known about the long-term neurodevelopmental outcomes of this therapy. Methods: Using a schedule of tapering doses of DEX similar to that used in premature infants, we examined the consequences of neonatal DEX treatment on hippocampal synaptic plasticity of infants and associative memory later in their lives. Results: Neonatal DEX treatment changed the direction of synaptic plasticity, favoring low-frequency, stimulation-induced, long-term depression and opposing the induction of long-term potentiation by high-frequency stimulation in adolescent (5-week-old) rats, but these alterations disappeared in young adult (8-week-old) rats. The effects of DEX on long-term depression and long-term potentiation were found to correlate with an increase in the autophosphorylation of Ca2+/ calmodulin-dependent protein kinase II and a decrease in the protein phosphatase 1 activity. Neonatal DEX treatment also disrupted memory retention in 5-week-old (but not 8-week-old) rats subjected to passive avoidance learning tasks. Interpretation: These results suggest that neonatal DEX treatment alters hippocampal synaptic plasticity and contextual fear memory formation in later life, but these impairments apparently are not permanent.",
author = "Lin, {Hsiao Ju} and Huang, {Chiung Chun} and Kuei-Sen Hsu",
year = "2006",
month = "6",
day = "1",
doi = "10.1002/ana.20885",
language = "English",
volume = "59",
pages = "939--951",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

Effects of neonatal dexamethasone treatment on hippocampal synaptic function. / Lin, Hsiao Ju; Huang, Chiung Chun; Hsu, Kuei-Sen.

In: Annals of Neurology, Vol. 59, No. 6, 01.06.2006, p. 939-951.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of neonatal dexamethasone treatment on hippocampal synaptic function

AU - Lin, Hsiao Ju

AU - Huang, Chiung Chun

AU - Hsu, Kuei-Sen

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Objective: Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Surprisingly, little is known about the long-term neurodevelopmental outcomes of this therapy. Methods: Using a schedule of tapering doses of DEX similar to that used in premature infants, we examined the consequences of neonatal DEX treatment on hippocampal synaptic plasticity of infants and associative memory later in their lives. Results: Neonatal DEX treatment changed the direction of synaptic plasticity, favoring low-frequency, stimulation-induced, long-term depression and opposing the induction of long-term potentiation by high-frequency stimulation in adolescent (5-week-old) rats, but these alterations disappeared in young adult (8-week-old) rats. The effects of DEX on long-term depression and long-term potentiation were found to correlate with an increase in the autophosphorylation of Ca2+/ calmodulin-dependent protein kinase II and a decrease in the protein phosphatase 1 activity. Neonatal DEX treatment also disrupted memory retention in 5-week-old (but not 8-week-old) rats subjected to passive avoidance learning tasks. Interpretation: These results suggest that neonatal DEX treatment alters hippocampal synaptic plasticity and contextual fear memory formation in later life, but these impairments apparently are not permanent.

AB - Objective: Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Surprisingly, little is known about the long-term neurodevelopmental outcomes of this therapy. Methods: Using a schedule of tapering doses of DEX similar to that used in premature infants, we examined the consequences of neonatal DEX treatment on hippocampal synaptic plasticity of infants and associative memory later in their lives. Results: Neonatal DEX treatment changed the direction of synaptic plasticity, favoring low-frequency, stimulation-induced, long-term depression and opposing the induction of long-term potentiation by high-frequency stimulation in adolescent (5-week-old) rats, but these alterations disappeared in young adult (8-week-old) rats. The effects of DEX on long-term depression and long-term potentiation were found to correlate with an increase in the autophosphorylation of Ca2+/ calmodulin-dependent protein kinase II and a decrease in the protein phosphatase 1 activity. Neonatal DEX treatment also disrupted memory retention in 5-week-old (but not 8-week-old) rats subjected to passive avoidance learning tasks. Interpretation: These results suggest that neonatal DEX treatment alters hippocampal synaptic plasticity and contextual fear memory formation in later life, but these impairments apparently are not permanent.

UR - http://www.scopus.com/inward/record.url?scp=33744819699&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744819699&partnerID=8YFLogxK

U2 - 10.1002/ana.20885

DO - 10.1002/ana.20885

M3 - Article

C2 - 16718693

AN - SCOPUS:33744819699

VL - 59

SP - 939

EP - 951

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 6

ER -