Modulation of fibroblast growth factor-2 by stress and corticosteroids: from developmental events to adult brain plasticity

doi:10.1016/S0165-0173(01)00128-X

Brain Research Reviews

Volume 37, Issues 1–3, November 2001, Pages 249-258

https://doi.org/10.1016/S0165-0173(01)00128-X Get rights and content

Abstract

Neurotrophic factors are a heterogeneous group of peptides that play important roles on brain function at different development stages. Basic fibroblast growth factor (FGF-2), one of these molecules, is highly expressed in developing and adult brain. Its expression can be regulated under different experimental situations and this may be relevant for cellular vulnerability and brain plasticity. Stress and glucocorticoid hormones produce short- and long-term effects on brain function, which can involve the regulation of specific neurotrophic factors within selected brain structures. Treatments with corticosterone or dexamethasone up-regulate FGF-2 expression in different rat brain regions as well as in cultured astroglial cells. A similar elevation of FGF-2 biosynthesis is also observed in several brain regions following an acute restraint stress. This response is rapid and transient and, as FGF-2 is neuroprotective, may represent a defense mechanism through which the brain may limit the deleterious effect of stress over time. Moreover exposure to corticosterone during late stage of embryonic life (E18–E20) produces a significant reduction of FGF-2 mRNA levels in the adult hippocampus of male rats as well as changes in its acute modulation in response to stress or corticosterone. These data suggest that stress-related events taking place during brain maturation can modulate the expression of FGF-2 within selected brain regions thus contributing to permanent structural and functional alterations leading to an increased vulnerability to challenging life events.

Introduction

Stress can be considered a general reaction of an organism, which can monitor internal and external conditions in order to develop proper coping strategies that will allow survival. The stress response occurs through multiple pathways involving hormones and neurotransmitters. The hypothalamic–pituitary–adrenal (HPA) system operates to control glucocorticoid hormones secreted by the adrenal glands, which are the most important steroid hormones secreted during stress. Glucocorticoids mobilize energy, increase cardiovascular tone, reinforce aspects of the immune system and modulate different systems of the body. However glucocorticoid hormones exert multiple effects on brain function and neuronal viability: such effects are thought to be relevant for several psychiatric disorders, such as depression, schizophrenia and posttraumatic stress disorders, which may involve complex alterations in brain plasticity, especially at the level of the hippocampal formation [36], [37], [62].

Section snippets

Stress, glucocorticoids and brain plasticity

The brain is indeed a key structure for the interpretation and response to stressful events. In the short run, elevation of glucocorticoids (or catecholamines) can be protective and facilitates the formation of a memory related to the stressful situation [40], [59]. However prolonged exposure to stress hormones can damage specific brain structures, such as the hippocampus, thus determining persistent functional deficits [39]. Corticosterone actions in the brain are mediated by type I

FGF-2 in developing and adult brain

FGF-2 is the prototype member of a large family of neurotrophic molecules existing in different protein isoforms (18, 21 and 22 kDa), which display selective subcellular localization thus implying different functional roles [5], [50]. FGF-2 binds to four related tyrosine kinase receptors (FGFR1–4), which exist in different splice variants and, in many respects, appear similar to other growth factor receptors [23]. FGF-2 is a potent angiogenic factor, may stimulate hematopoiesis and play an

Modulation of FGF-2 by glucocorticoid hormones: a comparison to neurotrophins

Since adrenal steroids and neurotrophic factors are important modulators of neuronal plasticity, it is feasible to hypothesize that the modulation of trophic factor expression may, at least in part, contribute to the effects brought about by these hormones on brain function. Several investigators have examined the expression of neurotrophins by circulating glucocorticoids. For example, adrenalectomy produces a significant reduction of nerve growth factor (NGF) and neurotrophin 3 (NT-3)

Modulation of FGF-2 and neurotrophins by stress

Since corticosteroids are the most important steroid hormones secreted during stress from the adrenal glands, it is expected that stress will also regulate the expression of neurotrophic molecules. Although the stress response involves activation of multiple pathways leading to increased release of neurotransmitters [48], the activation of the HPA axis represents the major hormonal component. There are substantial differences in the anatomical profile of trophic factor modulation following

Developmental events can influence the function of the HPA axis and brain plasticity in adulthood

It is well documented that during the perinatal period the development of an organism is subjected to complex environmental influences. Early work by Levine [29] has clearly demonstrated that early stimulation of neonatal rats affects their endocrine and behavioral responses later in life. Maternal care or early brief manipulation (handling) results in animals which are less emotional and, in general, better adapted and able to respond according to the demands of the environment [16]. These

Modulation of FGF-2 expression by prenatal exposure to glucocorticoids

As glucocorticoid hormones represent major players in stress-related events, we decided to investigate whether exposure to corticosterone during late pregnancy could interfere with the expression and regulation of FGF-2 in adult offspring.

Prenatal exposure to corticosterone did not produce any significant change in the body weight of male or female offspring, nor did it produce any change in the adrenal gland weight of adult animals (data not shown). The analysis of FGF-2 expression under basal

Conclusions

There are consistent data indicating that, among other trophic molecules, FGF-2 expression is strongly modulated under acute stress or exposure to corticosteroids. Moreover early exposure to these hormones produces persistent changes in the regulatory machinery of FGF-2. We propose that stress-related events taking place during brain maturation can modulate the expression of neurotrophic factors within selected brain regions thus contributing to permanent structural and functional alterations

Acknowledgements

We wish to thank Dr A. Baird for the generous gift of FGF-2 cDNA probe. Special thanks to Drs F. Ronchi and M. Spiti for contributing to part of this study.

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ReviewModulation of fibroblast growth factor-2 by stress and corticosteroids: from developmental events to adult brain plasticity

Abstract

Introduction

Section snippets

Stress, glucocorticoids and brain plasticity

FGF-2 in developing and adult brain

Modulation of FGF-2 by glucocorticoid hormones: a comparison to neurotrophins

Modulation of FGF-2 and neurotrophins by stress

Developmental events can influence the function of the HPA axis and brain plasticity in adulthood

Modulation of FGF-2 expression by prenatal exposure to glucocorticoids

Conclusions

Acknowledgements

Neuroscience

Mol. Brain Res.

FEBS Lett.

Exp. Neurol.

Curr. Opin. Neurobiol.

Brain Res.

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Mol. Brain Res.

Mol. Brain Res.

Brain Res.

Curr. Opin. Neurobiol.

J. Biol. Chem.

Mol. Brain Res.

Neuroscience

Mol. Brain Res.

Mol. Brain Res.

Dev. Brain Res.

Mol. Brain Res.

Psychoneuroendocrinology

Dev. Brain Res.

Neuron

Prog. Brain Res.

Adrenalectomy decreases nerve growth factor in young adult rat hippocampus

Proc. Natl. Acad. Sci. USA

Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo

Nature

Maternal glucocorticoid secretion mediates long-term effects of prenatal stress

J. Neurosci.

Biological roles of fibroblast growth factor-2

Endocr. Rev.

Basic fibroblast growth factor enters the nucleolus and stimulates the transcription of ribosomal genes in ABAE cells undergoing G0–G1 transition

Proc. Natl. Acad. Sci. USA

Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus

Endocrinology

Prenatal stress enhances stress- and corticotropin-releasing factor-induced stimulation of hippocampal acetylcholine release in adult rats

J. Neurosci.

Brain corticosteroid receptor balance in health and disease

Endocr. Rev.

Long-lasting induction of astrocytic basic fibroblast growth factor by repeated injections of amphetamine: blockade by concurrent treatment with a glutamate antagonist

J. Neurosci.

Requirement of endogenous basic fibroblast growth factor for sensitization to amphetamine

J. Neurosci.

Regulation of basic fibroblast growth factor and nerve growth factor mRNA by beta-adrenergic receptor activation and adrenal steroids in rat central nervous system

Mol. Pharmacol.

Review
Modulation of fibroblast growth factor-2 by stress and corticosteroids: from developmental events to adult brain plasticity