Chronic Stress Decreases the Number of Parvalbumin-Immunoreactive Interneurons in the Hippocampus: Prevention by Treatment with a Substance P Receptor (NK1) Antagonist

Czéh, Boldizsár; Simon, Mária; Hart, Marieke G. C. van der; Schmelting, Barthel; Hesselink, Mayke B.; Fuchs, Eberhard

doi:10.1038/sj.npp.1300581

Cited by 123 publications

(95 citation statements)

References 98 publications

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“…Furthermore, parvalbumin immunoreactive neurons are reduced in the hippocampus of tree shrews after chronic psychosocial stress (Czeh et al, 2005), as well as in Octodon degus after repeated separation stress (Seidel et al, 2008), whereas calbindin immunoreactive neurons were significantly reduced in the CA1 of the hippocampus of mice after inescapable electric foot shocks paradigm (Huang et al, 2010). On these bases, the defects of hippocampal GABAergic markers in SERT À/À animals may contribute to the anxious/depressive phenotype observed in these animals (Olivier et al, 2008).…”

Section: Discussionmentioning

confidence: 91%

Developmental Influence of the Serotonin Transporter on the Expression of Npas4 and GABAergic Markers: Modulation by Antidepressant Treatment

Guidotti

Calabrese

Auletta

et al. 2011

Neuropsychopharmacol

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Alterations of the serotonergic system are involved in the pathophysiology of mood disorders and represent an important target for its pharmacological treatment. Genetic deletion of the serotonin transporter (SERT) in rodents leads to an anxious and depressive phenotype, and is associated with reduced neuronal plasticity as indicated by decreased brain-derived neurotrophic factor (Bdnf) expression levels. One of the transcription factors regulating Bdnf is the neuronal PAS domain protein 4 (Npas4), which regulates activitydependent genes and neuroprotection, and has a critical role in the development of GABA synapses. On the basis of these premises, we investigated the expression of Npas4 and GABAergic markers in the hippocampus and prefrontal cortex of homozygous (SERT À/À ) and heterozygous (SERT + /À ) knockout rats, and analyzed the effect of long-term duloxetine treatment on the expression of these targets. We found that Npas4 expression was reduced in both the brain structures of adult SERT + /À and SERT À/À animals. This effect was already present in adolescent SERT À/À , and could be mimicked by prenatal exposure to the antidepressant fluoxetine. Moreover, SERT À/À rats showed a strong impairment of the GABAergic system, as indicated by the reduction of several markers, including the vesicular transporter (Vgat), glutamic acid decarboxylase-67 (Gad67), the receptor subunit GABA A receptor, gamma 2 (GABA A -g2), and calciumbinding proteins that label subgroups of the GABAergic neurons. Interestingly, chronic treatment with the antidepressant duloxetine was able to restore the physiological levels of Npas4 and GABAergic markers in SERT À/À rats, although some differences in the modulation of GABAergic genes exist between hippocampus and prefrontal cortex. Our results demonstrate that SERT knockout rats, an animal model of mood disorders, have reduced Npas4 expression that correlates with decreased expression of Bdnf exon I and IV. These changes lead to an impairment of the GABAergic system that may contribute to the anxious and depressive phenotype associated with inherited SERT downregulation.

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Section: Discussionmentioning

confidence: 91%

Developmental Influence of the Serotonin Transporter on the Expression of Npas4 and GABAergic Markers: Modulation by Antidepressant Treatment

Guidotti

Calabrese

Auletta

et al. 2011

Neuropsychopharmacol

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“…The heightened response to stress in peripubertal MAM rats would make these rats more vulnerable to the effect of stress and influence normal development of these structures. For example, parvalbumin interneurons are sensitive to stress (Czeh et al, 2005;Hu et al, 2010) and would likely be affected. And indeed, the loss of parvalbumin interneurons in the hippocampus initiated in juvenile rats and progressed into adulthood (Gill and Grace, 2014).…”

Section: Discussionmentioning

confidence: 99%

Amygdala Hyperactivity in MAM Model of Schizophrenia is Normalized by Peripubertal Diazepam Administration

Grace

2016

Neuropsychopharmacol

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In addition to prefrontal cortex (PFC) and hippocampus, amygdala may have a role in the pathophysiology of schizophrenia, given its pivotal role in emotion and extensive connectivity with the PFC and hippocampus. Moreover, abnormal activities of amygdala may be related to the anxiety observed in schizophrenia patients and at-risk adolescents. These at-risk subjects demonstrated heightened levels of anxiety, which are correlated with the onset of psychosis later in life. Similarly, rats that received methyl azoxymethanol acetate (MAM) gestationally exhibited higher levels of anxiety peripubertally. In the current study, the heightened anxiety was also observed in adult MAM animals, as well as higher firing rates of BLA neurons in both peripubertal and adult MAM rats. In addition, the power of BLA theta oscillations of adult MAM rats showed a larger increase in response to conditioned stimuli (CS). We showed previously that administration of the antianxiety drug diazepam during the peripubertal period prevents the hyperdopaminergic state in adult MAM rats. In this study, we found that peripubertal diazepam treatment reduced heightened anxiety, decreased BLA neuron firing rates and attenuated the CS-induced increase in BLA theta power in adult MAM rats, supporting a persistent normalization by this treatment. This study provides a link between BLA hyperactivity and anxiety in schizophrenia model rats and that circumvention of stress may prevent the emergence of pathology in the adult.

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“…An intensive line of research suggested that stress and excessive glucocorticoids can have such effects and eventually lead to overt neuronal loss by exacerbating the neurotoxicity that is induced by other hippocampal insults [79]. A recent study presented evidence suggesting that chronic (5 weeks) psychosocial stress in tree shrews might lead to decreased number of GABAergic interneurons in all hippocampal areas except in CA1 [80]. Interestingly, antidepressant treatment, notably by NK1R (a novel neurokinin 1 receptor antagonist), and partially by the selective serotonin reuptake inhibitor (SSRI) fluoxetine prevented the stress-induced reduction of the number of interneurons, when administered from the second week of stress [80].…”

Section: Clinical and Preclinical Evidence For The Network Hypothesismentioning

confidence: 99%

A Model for the Involvement of Neural Cell Adhesion Molecules in Stress-Related Mood Disorders

Sandi

Bisaz²

2007

Neuroendocrinology

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Critical interactions between genetic and environmental factors – among which stress is one of the most potent non-genomic factors – are involved in the development of mood disorders. Intensive work during the past decade has led to the proposal of the network hypothesis of depression [Castren E: Nat Rev Neurosci 2005;6:241–246]. In contrast to the earlier chemical hypothesis of depression that emphasized neurochemical imbalance as the cause of depression, the network hypothesis proposes that problems in information processing within relevant neural networks might underlie mood disorders. Clinical and preclinical evidence supporting this hypothesis are mainly based on observations from depressed patients and animal stress models indicating atrophy (with basic research pointing at structural remodeling and decreased neurogenesis as underlying mechanisms) and malfunctioning of the hippocampus and prefrontal cortex, as well as the ability of antidepressant treatments to have the opposite effects. A great research effort is devoted to identify the molecular mechanisms that are responsible for the network effects of depression and antidepressant actions, with a great deal of evidence pointing at a key role of neurotrophins (notably the brain-derived neurotrophic factor) and other growth factors. In this review, we present evidence that implicates alterations in the levels of the neural cell adhesion molecules of the immunoglobulin superfamily, NCAM and L1, among the mechanisms contributing to stress-related mood disorders and, potentially, in antidepressant action.

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Chronic Stress Decreases the Number of Parvalbumin-Immunoreactive Interneurons in the Hippocampus: Prevention by Treatment with a Substance P Receptor (NK1) Antagonist

Cited by 123 publications

References 98 publications

Developmental Influence of the Serotonin Transporter on the Expression of Npas4 and GABAergic Markers: Modulation by Antidepressant Treatment

Developmental Influence of the Serotonin Transporter on the Expression of Npas4 and GABAergic Markers: Modulation by Antidepressant Treatment

Amygdala Hyperactivity in MAM Model of Schizophrenia is Normalized by Peripubertal Diazepam Administration

A Model for the Involvement of Neural Cell Adhesion Molecules in Stress-Related Mood Disorders

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