Neurochemical Research

, Volume 35, Issue 7, pp 1038–1049

Chronic Unpredictable Stress Before Pregnancy Reduce the Expression of Brain-Derived Neurotrophic Factor and N-Methyl-D-Aspartate Receptor in Hippocampus of Offspring Rats Associated with Impairment of Memory

  • Yuejun Huang
  • Xuechuan Shi
  • Hongwu Xu
  • Hanhua Yang
  • Tian Chen
  • Sihong Chen
  • Xiaodong Chen
Original Paper

DOI: 10.1007/s11064-010-0152-0

Cite this article as:
Huang, Y., Shi, X., Xu, H. et al. Neurochem Res (2010) 35: 1038. doi:10.1007/s11064-010-0152-0

Abstract

To investigate the effect of stress before pregnancy on memory function and serum corticosterone (COR) levels, as well as the expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate (NMDA) 2A (NR2A) and 2B (NR2B) receptors in the hippocampus of the offspring rats when they were 2 months postnatally. Adult female Sprague-Dawley (SD) rats were divided randomly into two groups: control group (n = 8) and chronic unpredictable stress (CUS) group (n = 12). All rats were tested in the open field test and sucrose intake test before and after CUS. The memory function of their offspring were tested in the Morris water maze. Serum COR levels were determined by using a standard radioimmunoassay kit. The expression of BDNF, NR2A and NR2B in the hippocampus of the offspring rats were studied by immunoreactivity quantitative analysis and real-time RT-PCR. (1) Following CUS, reduced open field test activity and decreased sucrose consumption were observed relative to controls. (2) The Morris water maze task demonstrated increased escape latency in the offspring rats of CUS group relative to controls (P < 0.01). No-platform probe testing showed reduced crossings for offspring of CUS relative to controls (P < 0.05). (3) CUS induced a significant increase in serum COR levels of the offspring rats (P < 0.01), but no difference was observed in the body or brain weight between the offspring of the two groups. (4) Immunoreactivity quantitative analysis shows that BDNF and NR2B in the offspring of CUS group was decreased in the CA3 and DG regions of the hippocampus compared to the control group offspring, but NR2A levels were not altered between the offspring of the two groups. (5) Real-time RT-PCR demonstrated that BDNF and NR2B mRNAs were significantly decreased in the offspring of the CUS group compared with the control group (P < 0.01). No significant difference in the levels of NR2A mRNA was detected between offspring of CUS and offspring of control groups. In our study, pregestational stress can increase serum corticosterone levels and reduce the expression of BDNF and NR2B in the hippocampus of offspring. These alterations are associated with impairment of memory in the adult offspring. These data suggest that, stress before pregnancy might have a profound influence on brain development of offspring, that may persist into and be manifested in adulthood.

Keywords

Stress Offspring Memory Corticosterone Brain-derived neurotrophic factor N-methyl-D-aspartate 

Abbreviations

ANOVA

Analysis of variance

BDNF

Brain-derived neurotrophic factor

COR

Corticosterone

CUS

Chronic unpredictable stress

CRH

Corticotropin-releasing hormone

E

Embryonic

EL

Escape latency

GCs

Glucocorticoids

GR

Glucocorticoid receptors

HPA

Hypothalamic-pituitary-adrenal

LTP

Long-term potentiation

NMDA

N-methyl-D-aspartate

NR

N-methyl-D-aspartate receptor

PND

Postnatal day

RT-PCR

Reverse-transcriptase polymerase chain reaction

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Yuejun Huang
    • 1
  • Xuechuan Shi
    • 1
  • Hongwu Xu
    • 2
  • Hanhua Yang
    • 1
  • Tian Chen
    • 1
  • Sihong Chen
    • 1
  • Xiaodong Chen
    • 1
  1. 1.The Department of PediatricsThe Second Affiliated Hospital of Medical College of Shantou UniversityShantouChina
  2. 2.The Department of NeurosurgeryThe Second Affiliated Hospital of Medical College of Shantou UniversityShantouChina

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