Original articleChronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis
Introduction
Repetitive transcranial magnetic stimulation (rTMS) is currently being evaluated in the treatment of major depression in various clinical trials. Indeed, several lines of evidence resulting from both preclinical Fleischmann et al 1995, Zyss et al 1997, Keck et al 2001 and clinical Padberg et al 1999, Berman et al 2000, George et al 1999 studies support the notion that rTMS may have antidepressant properties; however, there is still a profound lack of knowledge concerning the putative effects at the molecular and cellular level underlying the observed clinical effects (Post and Keck 2001). Previously, we demonstrated that in certain conditions, long-term rTMS of left frontal brain regions may induce neuroprotective-like effects both in vitro and in vivo (Post et al 1999). In addition, we could show that long-term rTMS induces changes in the expression of brain-derived neurotrophic factor (BDNF) and cholecystokinin, which are similar to those reported after antidepressant drug treatment and electroconvulsive seizures (Müller et al 2000). These data support the hypothesis that a common molecular mechanism may underlie different antidepressant treatment strategies and emphasize the importance of animal experiments in understanding the neurobiological changes induced by rTMS.
It is widely accepted that chronic stress increases the risk of developing and is associated with affective disorders (Kendler et al 1999). Therefore, a hypothesis relating stress hormone dysregulation to causality of depression was proposed suggesting that antidepressants may act through normalization of the hypothalamic-pituitary-adrenocortical (HPA) changes (Holsboer 2000). In line with the above are the findings on chronic rTMS-induced changes in stress-induced corticotropin (ACTH) and corticosterone plasma levels in rats Keck et al 2000a, Keck et al 2001 providing evidence that rTMS of frontal brain regions attenuates the stress-induced activity of the HPA system. Moreover, basal corticosterone plasma concentrations were reported to be lowered after a single rTMS application (Hedges et al 2002).
Proliferation and maturation of functional neurons have been demonstrated to occur at a significant rate in the adult hippocampus in many different mammalian species including humans Eriksson et al 1998, Gross 2000, Van Praag et al 2002. Moreover, adult neurogenesis is an extremely dynamic process that is regulated in both a positive and negative manner by neuronal activity and environmental factors (Gould et al 2000). In addition, exposure to psychotropic drugs or stress regulates the rate of neurogenesis in adult brain, suggesting a possible role for neurogenesis in the pathophysiology and treatment of neurobiological illnesses such as depression and posttraumatic stress disorder Duman et al 1999, Duman et al 2001.
The aim of the present study was to determine whether a concomitant rTMS treatment might exert a beneficial effect on the psychosocial stress-induced decrease in adult neuron production and/or survival of the newly generated cells in the hippocampal dentate gyrus. As granule neuron production and survival is highly dependent on circulating levels of glucocorticoid hormones, we additionally monitored the effects of rTMS on plasma ACTH and corticosterone levels.
Section snippets
Animals
The animal studies were conducted in accordance with the Guide for the Care and Use of Laboratory Animals of the Government of Bavaria, and NIH guidelines. Three-month-old male Wistar rats (n = 48) were used. Animals were housed in groups of six under standard laboratory conditions in the breeding unit of the Max Planck Institute of Psychiatry under standard laboratory conditions (12/12 hours light/dark cycle, food and water ad libitum). Two weeks before the experiment, all rats were housed
Stress-induced elevation of ACTH and corticosterone is normalized by rTMS treatment
To characterize the basal activity of the HPA system, blood samples were taken for hormone concentration measurements at the end of the 18 days of treatment. The mean values of ACTH and corticosterone (cort) levels in each group are displayed in Figure 1. Basal plasma ACTH and cort levels were comparable in the control and control + rTMS rats. Exposure to chronic psychosocial stress induced a substantial elevation both in plasma ACTH (+94%) and corticosterone (+97%) levels. Two-way ANOVA
Discussion
The present study was designed to examine the effects of concomitant rTMS treatment on plasma stress hormone levels and on neurogenesis in the hippocampal dentate gyrus of the adult rat during chronic psychosocial stress. Repetitive transcranial magnetic stimulation (20 Hz) of frontal brain regions normalized the stress-induced elevation of plasma ACTH and corticosterone, herewith confirming our previous results Keck et al 2000a, Keck et al 2001. An important finding of this study is that the
Acknowledgements
The authors would like to thank Monika Rücker for skillful technical assistance. The magnetic stimulation device was kindly provided by DANTEC/Medtronic, Skovlunde, Denmark.
This project was supported by the German Federal Research Ministry within the promotional emphasis “Competence Nets in Medicine” Kompetenznetz Depression & Suizidalität; subproject 4.5 (MEK), and the network “Gepulste Magnet-Stimulation des Gehirns in der Therapie Neuropsychologischer Erkankungen” (0311467B) (EF). AKF was
References (51)
- et al.
A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression
Biol Psychiatry
(2000) - et al.
Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus
Neuroscience
(1994) - et al.
Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat
Neuroscience
(1993) - et al.
Cellular targets and trophic functions of neurotrophin-3 in the developing rat hippocampus
Neuron
(1992) - et al.
Neural plasticity to stress and antidepressant treatment
Biol Psychiatry
(1999) - et al.
The influence of females upon aggression in domesticated male rats (Rattus norvegicus)
Anim Behav
(1977) - et al.
The effect of transcranial magnetic stimulation of rat brain on behavioral models of depression
Brain Res
(1995) - et al.
Regulation of hippocampal neurogenesis in adulthood
Biol Psychiatry
(2000) - et al.
Transcranial magnetic stimulation (TMS) effects on testosterone, prolactin, and corticosterone in adult male rats
Biol Psychiatry
(2002) The corticosteroid receptor hypothesis of depression
Neuropsychopharmacology
(2000)
Repetitive transcranial magnetic stimulation induces active coping strategies and attenuates the neuroendocrine stress response in rats
J Psychiatr Res
Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders
Peptides
Neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation in a psychopathological animal model are suggestive of antidepressant-like effects
Neuropsychopharmacology
Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats
Brain Res
Increased neurogenesis in a model of electroconvulsive therapy
Biol Psychiatry
Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain
Neuropsychopharmacology
Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depressionComparative study of fast, slow and sham rTMS
Psychiatry Res
Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression
Lancet
Transcranial magnetic stimulation as a therapeutic tool in psychiatryWhat do we know about the neurobiological mechanisms?
J Psychiatr Res
The brain mineralocorticoid receptorGreedy for ligand, mysterious in function
Eur J Pharmacol
Neurogenesis in the dentate gyrus of the rat following electroconvulsive shock seizures
Exp Neurol
Preliminary comparison of behavioral and biochemical effects of chronic transcranial magnetic stimulation and electroconvulsive shock in the rat
Biol Psychiatry
The control on neuronal birth and survival
Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus
J Neurosci
Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway
Neuroscience
Cited by (297)
Astrocyte-derived lactate in stress disorders
2024, Neurobiology of DiseaseEmotional behaviors as well as the hippocampal reelin expression in C57BL/6N male mice chronically treated with corticosterone
2023, Pharmacology Biochemistry and BehaviorDorsal Dentate Gyrus, a Key Regulator for Mood and Psychiatric Disorders
2023, Biological PsychiatryInflammation increases the development of depression behaviors in male rats after spinal cord injury
2021, Brain, Behavior, and Immunity - Health