Elsevier

Neuroscience

Volume 199, 29 December 2011, Pages 491-500
Neuroscience

Regeneration, Repair, and Developmental Neuroscience
Research Paper
Nerve growth factor (NGF) immunoreactive neurons in the juvenile rat hippocampus: response to acute and long-term high-light open-field (HL-OF) or forced swim (FS) stress stimulation

https://doi.org/10.1016/j.neuroscience.2011.10.013Get rights and content

Abstract

This study aimed at examining and comparing the influence of two different stress stimuli on the density (number of cells/mm2) of nerve growth factor (NGF) containing neurons in the hippocampal CA1 and CA3 pyramidal cell layers and the dentate gyrus (DG) granule cell layer in juvenile rats (P28; P-postnatal day). The high-light open-field (HL-OF) test and forced swim (FS) test were employed to investigate the effects of a single, 15-min acute exposure and repeated (15 min daily for 21 days) long-term exposure to stress. In order to detect NGF-ir neurons, immunohistochemical (-ir) techniques were used. In comparison with nonstressed animals, acute and long-term HL-OF or FS stimulation resulted in a marked increase (P<0.001) in the density of NGF-ir containing cells in all the hippocampal structures. The frequency of stress application (acute vs. long-term), however, did not have a substantial impact on the studied parameter, with the exception of the CA3 sector, where a decreased density (P<0.001) of NGF-ir neurons was observed after long-term exposure to FS. It may be concluded that a rise in the density of NGF-ir neurons in the juvenile rat hippocampus after exposure to HL-OF or FS stressors could have affected the activity of the hypothalamic-pituitary-adrenocortical (HPA) stress axis. Prolonged HL-OF or FS stress was probably aggravating enough not to trigger the habituation process. The type of stressor applied (HL-OF vs. FS) was not essentially a factor determining the density of NGF-ir cells in the hippocampus.

Highlights

▶NGF is expressed in hippocampal cells of juvenile rats. ▶We studied the effects of acute and long-term HL-OF and FS stress on NGF-ir cells. ▶Both types of stimulations led to an increase in the density of NGF-ir cells. ▶After long-term HL-OF or FS stress habituation did not occur in juvenile rats.

Section snippets

Animals

Twenty-five Wistar Han rats were housed with their mothers (one mother with five pups per cage) from birth until the end of the experiment, when they reached 28 days of age (P28; P-postnatal day). The animals were kept in impoverished polycarbonate cages (T. IV, 56 cm×36 cm ×20 cm+7 cm cage lid) containing only sawdust on the floor, but they had free access to water and food pellets. Temperature (21±1 °C) and lighting (light on from 7:00 am–7:00 pm) regimens were maintained at constant levels

NGF-immunoreactive cells in hippocampal structures (CA1, CA3, and DG) in P28 control rats

In juvenile (P28) control rats, NGF-ir cells were observed in the pyramidal layer of the CA1 and CA3 areas, as well as in the granular layer of the DG subregion of the hippocampus (Fig. 1, Fig. 2, Fig. 3A, Fig. 1, Fig. 2, Fig. 3B–B′). The density of NGF-ir cells in CA1 and CA3 was comparable (CA1: 1403.62±95.54, CA3: 1348.13±87.27), but in DG the number was slightly higher (1738.19±82.06) (Fig. 1, Fig. 2, Fig. 3A). Varying intensity of NGF immunostaining was observed in the somata (cytoplasm)

Discussion

Our experiment demonstrated that both acute and long-term HL-OF or FS stress resulted in a statistically significant increase in the density of NGF-ir neurons in juvenile (P28) rats in all investigated hippocampal regions.

An immunohistochemical study showed that NGF-ir neurons occurred in the pyramidal cell layers of CA1 and CA3 and in the DG granular cell layer of the unstressed juvenile rats. The presence of NGF-immunoreactive cells in these areas during early postnatal life has been reported

Conclusions

Applied stress stimuli (HL-OF or FS) led to an increase in the density of NGF-ir neurons in the hippocampus of juvenile rats, which might have affected HPA axis activity. In hippocampal structures acute vs. chronic stress stimulation was not reflected in the changes of the density of NGF containing neurons after HL-OF or FS. Long-term HL-OF or FS stressors were probably so aggravating that the phenomenon of habituation did not occur. The type of stress stimulus (HL-OF vs. FS) was generally not

Acknowledgments

This study was supported by funds from the Polish Committee of Scientific Research (research project No N401 011 31/0168). We would like to thank, Dr. Jerzy Diewiątkowski for statistic analysis.

References (89)

  • F. Cirulli et al.

    Early maternal separation increases NGF expression in the developing rat hippocampus

    Pharmacol Biochem Behav

    (1998)
  • G. Conti et al.

    Immunohistochemical evaluation of the protein expression of nerve growth factor and its TrkA receptor in rat limbic regions following electroshock seizures

    Neurosci Res

    (2009)
  • L.H. Conti et al.

    Rat strain-dependent effects of repeated stress on the acoustic startle response

    Behav Brain Res

    (2003)
  • J.F. Cryan et al.

    Assessing antidepressant activity in rodents: recent developments and future needs

    Trends Pharmacol Sci

    (2002)
  • R.S. Duman et al.

    A neurotrophic model for stress-related mood disorders

    Biol Psychiatry

    (2006)
  • L. Enthoven et al.

    Effects of maternal deprivation of CD1 mice on performance in the water maze and swim stress

    Behav Brain Res

    (2008)
  • K.A. Fenoglio et al.

    Hippocampal neuroplasticity induced by early-life stress: functional and molecular aspects

    Front Neuroendocrinol

    (2006)
  • E. Fuchs et al.

    Chronic social stress: effects on limbic brain structures

    Physiol Behav

    (2003)
  • M. Hadjiconstantinou et al.

    Changes in plasma nerve growth factor levels in older adults associated with chronic stress

    J Neuroimmunol

    (2001)
  • F.S. Hall et al.

    Differential basis of strain and rearing effects on open-field behavior in Fawn Hooded and Wistar rats

    Physiol Behav

    (2000)
  • R. Hellweg et al.

    Moderate lesion of the rat cholinergic septohippocampal pathway increases hippocampal nerve growth factor synthesis: Evidence for long-term compensatory changes?

    Brain Res Mol Brain Res

    (1997)
  • J.P. Herman et al.

    Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness

    Front Neuroendocrinol

    (2003)
  • M. Hristova et al.

    Metabolic syndrome—neurotrophic hypothesis

    Med Hypotheses

    (2006)
  • V. Lessmann et al.

    Neurotrophin secretion: current facts and future prospects

    Prog Neurobiol

    (2003)
  • L. Marais et al.

    Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus

    Neurosci Res

    (2008)
  • C.M. McCormick et al.

    Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory

    Prog Neuropsychopharmacol Biol Psychiatry

    (2010)
  • C.M. McCormick et al.

    Investigations of HPA function and the enduring consequences of stressors in adolescence in animal models

    Brain Cogn

    (2010)
  • C.M. McCormick et al.

    Effects of chronic social stress in adolescence on anxiety and neuroendocrine response to mild stress in male and female rats

    Behav Brain Res

    (2008)
  • B.S. McEwen

    Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators

    Eur J Pharmacol

    (2008)
  • P. Muigg et al.

    Altered brain activation pattern associated with drug-induced attenuation of enhanced depression-like behavior in rats bred for high anxiety

    Biol Psychiatry

    (2007)
  • J.M. Pizarro et al.

    Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice

    Brain Res

    (2004)
  • L. Prut et al.

    The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review

    Eur J Pharmacol

    (2003)
  • R.D. Romeo et al.

    Pubertal maturation and time of day differentially affect behavioral and neuroendocrine responses following an acute stressor

    Horm Behav

    (2006)
  • S. Scaccianoce et al.

    Nerve growth factor brain concentration and stress: changes depend on type of stressor and age

    Int J Dev Neurosci

    (2000)
  • O. Schulte-Herbrüggen et al.

    Differential regulation of nerve growth factor and brain-derived neurotrophic factor in a mouse model of learned helplessness

    Exp Neurol

    (2006)
  • N. Sousa et al.

    Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement

    Neuroscience

    (2000)
  • E.A. Stone et al.

    Reduced evoked fos expression in activity-related brain regions in animal models of behavioral depression

    Prog Neuropsychopharmacol Biol Psychiatry

    (2007)
  • L. Tapia-Arancibia et al.

    Physiology of BDNF: focus on hypothalamic function

    Front Neuroendocrinol

    (2004)
  • S. Von Richthofen et al.

    Effects of different kinds of acute stress on nerve growth factor content in rat brain

    Brain Res

    (2003)
  • J.I. Webster Marketon et al.

    Stress hormones and immune function

    Cell Immunol

    (2008)
  • S.W. Zhu et al.

    Influence of differential housing on emotional behaviour and neurotrophin levels in mice

    Behav Brain Res

    (2006)
  • M. aan het Rot et al.

    Neurobiological mechanisms in major depressive disorder

    CMAJ

    (2009)
  • J.P. Aggleton et al.

    Contrasting hippocampal and perirhinal cortex function using immediate early gene imaging

    Q J Exp Psychol

    (2005)
  • D.G. Amaral et al.

    Hippocampal formation

  • Cited by (0)

    View full text