Elsevier

Neuroscience Research

Volume 53, Issue 2, October 2005, Pages 129-139
Neuroscience Research

Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly

https://doi.org/10.1016/j.neures.2005.06.008Get rights and content

Abstract

Daily restraint for 3 weeks was shown to atrophy dendrites of hippocampal pyramidal neurons in rats. Brain-derived neurotrophic factor (BDNF), which maintains neuronal survival and morphology, has been shown to decrease in response to acute stress. Plasma glucocorticoid (GC) and serotonergic projections from the raphe nuclei play major roles in reducing BDNF synthesis in the hippocampus. We investigated BDNF mRNA levels there, together with plasma GC levels, GC receptors in the hippocampus/hypothalamus and 5-HT synthesizing enzyme, tryptophan hydroxylase in the raphe nuclei, in animals chronically stressed for 1–3 weeks, using in situ hybridization and immunohistochemistry. In these animals, BDNF mRNA levels were significantly decreased in the hippocampus after 6 h of restraint, but the ability of restraint to reduce BDNF synthesis seemed less robust than that seen in acute stress models. HPA axis response to stress in these animals assessed by plasma GC levels was delayed and sustained, and the GC receptor in the paraventricular hypothalamic nucleus was increased at 1 week. Tryptophan hydroxylase immunoreactivity was increased in the median raphe nucleus at 2–3 weeks. Repetitive stress-induced reduction of BDNF may partly contribute to the neuronal atrophy/death and reduction of hippocampal volume observed both in animals and humans suffering chronic stress and/or depression.

Section snippets

Experimental animals

Male Sprague–Dawley rats were purchased from SLC Japan, and housed two rats per cage at least for 1 week before they were used for experiment. All animals were maintained with free access to food and tap water and under standard conditions, with lights on between 08:00 h and 20:00 h and room temperature controlled at 24 °C. All the experiments were approved by the Animal Research Committee of Wakayama Medical University and carried out in accordance with the National Institute of Health Guide for

Effects of repeated stress on the gain in body weight and HPA axis response

Rats in 1–3W-stress groups showed significant reduction in body weight gain compared to the unstressed controls. At the end of 1–3 weeks of stress period (8 weeks of age), the average body weights of rats were as follows: 302.3 ± 5.5 g (the control group), 243.7 ± 5.6 g (1W-stress group), 215.7 ± 3.9 g (2W-stress group) and 206.7 ± 4.6 g (3W-stress group). The average daily food intake in 3W-stress group was about 25% less than that in the control group. They screamed and struggled to escape for the first

Discussion

The present study has demonstrated that immediately after the last session of restraint repeated for 1–3 weeks, BDNF mRNA in the hippocampus showed significant reduction compared to the controls. Such a periodic reduction in hippocampal BDNF mRNA induced by repetitive restraints may possibly contribute to the hippocampal neuronal atrophy observed in this stress model (Watanabe et al., 1992). The hippocampal BDNF mRNA is negatively correlated with plasma GC levels. It is well documented that

Acknowledgement

This work was supported by Grant-in-Aid (13480253) for Scientific Research (B) from The Ministry of Education, Culture, Sports, Science and Technology.

References (49)

  • M. Nakazato et al.

    Decreased levels of serum brain-derived neurotrophic factor in female patients with eating disorders

    Biol. Psychiatry

    (2003)
  • M.J. Schaaf et al.

    Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone

    Brain Res.

    (1998)
  • M.J. Schaaf et al.

    Circadian variation in BDNF mRNA expression in the rat hippocampus

    Mol. Brain Res.

    (2000)
  • R. Schmidt-Kastner et al.

    Comparative study of brain-derived neurotrophic factor messenger RNA and protein at the cellular level suggests multiple roles in hippocampus, striatum and cortex

    Neuroscience

    (1996)
  • P.M. Schwartz et al.

    Abnormal cerebellar development and foliation in BDNF−/− mice reveals a role for neurotrophins in CNS patterning

    Neuron

    (1997)
  • E. Shimizu et al.

    Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants

    Biol. Psychiatry

    (2003)
  • V.B. Singh et al.

    Sound stress activation of tryptophan hydroxylase blocked by hypophysectomy and intracranial RU 38486

    Eur. J. Pharmacol.

    (1994)
  • T. Ueyama et al.

    Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain

    Neurosci. Res.

    (1997)
  • S. Umemoto et al.

    Chronic glucocorticoid administration as well as repeated stress affects the subsequent acute immobilization stress-induced expression of immediate early genes but not that of NGFI-A

    Neuroscience

    (1997)
  • V.A. Vaidya et al.

    Role of 5-HT2A receptors in the stress-induced down-regulation of brain-derived neurotrophic factor expression in rat hippocampus

    Neurosci. Lett.

    (1999)
  • Y. Watanabe et al.

    Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons

    Brain Res.

    (1992)
  • C.S. Woolley et al.

    Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons

    Brain Res.

    (1990)
  • E.C. Azmitia et al.

    An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat

    J. Comp. Neurol.

    (1978)
  • J.D. Bremner et al.

    MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder

    Am. J. Psychiatry

    (1995)
  • Cited by (0)

    View full text