Systemic tumor necrosis factor-alpha decreases brain stimulation reward and increases metabolites of serotonin and dopamine in the nucleus accumbens of mice

Heesch, Floor van; Prins, Jolanda; Korte-Bouws, G.A.H.; Westphal, Koen G.C.; Lemstra, Suzanne; Olivier, Berend; Kraneveld, Aletta D.; Korte, S. Mechiel

doi:10.1016/j.bbr.2013.07.038

Cited by 46 publications

(20 citation statements)

References 29 publications

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“…Recently, it has been demonstrated that TNF-α raised the brain monoamine metabolism, which caused anhedonia in mice. TNF-α has elevated the dopamine metabolite homovanillic acid without disturbing dopamine levels itself [ 86 ]. On the basis of above-mentioned observation, TNF-α not only enhanced serotonin transporter activity, but also the activity of dopamine transporter in the brain, resulting in depression symptoms.…”

Section: The Pathophysiologic Role Of Tnf-α In Depressionmentioning

confidence: 99%

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

Zhang

Baloch

2016

IJMS

164

100

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Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α), play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies.

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Section: The Pathophysiologic Role Of Tnf-α In Depressionmentioning

confidence: 99%

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

Zhang

Baloch

2016

IJMS

164

100

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“…TNF- α, IL-6, IL-1) as well as decreased expression of brain derived neurotrophic factor (BDNF) in the hippocampus [ 54 ]. The peripheral administration of TNF-α in rodents results in anhedonic behavior in conjunction with an increase in extracellular level of serotonin metabolites in the nucleus accumbens [ 55 ]. It is well documented that cytokines, including TNF-α, induce the enzyme indoleamine 2, 3- dioxygenase (IDO), which leads to serotonin deprivation by converting tryptophan in kynurenine (KYN).…”

Section: The Role Of Tnf-α In the Patho-physiology Of Mddmentioning

confidence: 99%

The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments

Bortolato¹,

Carvalho²,

Soczynska³

et al. 2015

117

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Abstract:Major depressive disorder is a highly prevalent, chronic and recurring disorder, associated with substantial impairment in cognitive and interpersonal functions. Accumulating evidence suggests that inflammatory processes play an important role in the etio-pathogenesis, phenomenology, comorbidity and treatment of MDD. Suboptimal remission rates and the persistence of cognitive deficits contribute to functional impairment in MDD inviting the need for the development of mechanistically novel and domain specific treatment approaches. The MEDLINE/ Pubmed database was searched from inception to February, 9 th , 2014 with combinations of the following search terms: 'TNF-alpha', 'depression', 'infliximab', 'etanercept', 'adalimumab', 'golimumab' and 'certolizumab'. Preclinical and clinical evidence linking TNF-α to MDD pathophysiology were reviewed as well as the current status of TNF-α modulators as novel agents for the treatment of MDD. Experimental models and clinical studies provide encouraging preliminary evidence for the efficacy of TNF-α antagonists in mitigating depressive symptoms and improving cognitive deficits. Further studies are warranted to confirm these data in larger randomized controlled trials in primary psychiatric populations. Translational research provides a promising perspective that may aid the development and/or repurposing of mechanism-based treatments for depressive symptoms and cognitive impairment in MDD.

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“…in non-anaesthetized mice. TNF was reconstituted in dH 2 O vehicle and, based on previous studies (Bluthé et al, 1994;van Heesch et al, 2013), injected daily at a concentration of 20 or 40 ng/g body weight (in a 25 g mouse, equivalent to 0.5 and 1.0 μg/day, respectively) on consecutive days. Mice were maintained in littermate pairs with both mice per pair assigned to the same dose group.…”

Section: Experiments With Repeated Ip Tnf Injectionmentioning

confidence: 99%

“…Whilst only a small number of such studies have been conducted to date, they have yielded supportive evidence for important TNF effects. In mice, acute TNF administration in the periphery led to reduced body weight and less social exploration (Bluthé et al, 1994) and reduced operant self-stimulation of lateral hypothalamus (van Heesch et al, 2013). Acute delivery of TNF into the lateral brain ventricles (intracerebroventricular, i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

Differential effects of peripheral and brain tumor necrosis factor on inflammation, sickness, emotional behavior and memory in mice

Klaus

Paterna

Marzorati

et al. 2016

Brain, Behavior, and Immunity

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Tumor necrosis factor alpha (TNF) is increased in depression and clinical-trial evidence indicates that blocking peripheral TNF has some antidepressant efficacy. In rodents, peripheral or intracerebroventricular TNF results in sickness e.g. reduced body weight, altered emotional behavior and impaired memory. However, the underlying pathways and responsible brain regions are poorly understood. The aim of this mouse study was to increase understanding by comparing the effects of sustained increases in TNF in the circulation, in brain regions impacted by increased circulating TNF, or specific brain regions. Increased peripheral TNF achieved by repeated daily injection (IP-TNF) or osmotic pump resulted in decreased body weight, decreased saccharin (reward) consumption, and increased memory of an aversive conditioned stimulus. These effects co-occurred with increased plasma interleukin-6 and increased IPderived TNF in brain peri-ventricular regions. An adenovirus-associated viral TNF vector (AAV-TNF) was constructed, brain injection of which resulted in dose-dependent, sustained and region-specific TNF expression, and was without effect on blood cytokine levels. Lateral ventricle AAV-TNF yielded increased TNF in the same brain regions as IP-TNF. In contrast to IP-TNF it was without effect on body weight, saccharin consumption and fear memory, although it did increase anxiety. Hippocampal AAV-TNF led to decreased body weight. It increased conditioning to but not subsequent memory of an aversive context, suggesting impaired consolidation; it also increased anxiety. Amygdala AAV-TNF was without effect on body weight and aversive stimulus learning-memory, but reduced saccharin consumption and increased anxiety. This study adds significantly to the evidence that both peripheral and brain region-specific increases in TNF lead to both sickness and depression-and anxiety disorder-relevant behavior and do so via different pathways. It thereby highlights the complexity in terms of indirect and direct pathways via which increased TNF can act and which need to be taken into account when considering it as a therapeutic target. AbstractTumor necrosis factor alpha (TNF) is increased in depression and clinical-trial evidence indicates that blocking peripheral TNF has some antidepressant efficacy. In rodents, peripheral or intracerebroventricular TNF results in sickness e.g. reduced body weight, altered emotional behavior and impaired memory. However, the underlying pathways and responsible brain regions are poorly understood. The aim of this mouse study was to increase understanding by comparing the effects of sustained increases in TNF in the circulation, in brain regions impacted by increased circulating TNF, or specific brain regions.Increased peripheral TNF achieved by repeated daily injection (IP-TNF) or osmotic pump resulted in decreased body weight, decreased saccharin (reward) consumption, and increased memory of an aversive conditioned. These effects co-occurred with increased plasma interleukin-6 and increased I...

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Systemic tumor necrosis factor-alpha decreases brain stimulation reward and increases metabolites of serotonin and dopamine in the nucleus accumbens of mice

Cited by 46 publications

References 29 publications

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments

Differential effects of peripheral and brain tumor necrosis factor on inflammation, sickness, emotional behavior and memory in mice

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Systemic tumor necrosis factor-alpha decreases brain stimulation reward and increases metabolites of serotonin and dopamine in the nucleus accumbens of mice

Cited by 46 publications

References 29 publications

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

The Involvement of TNF-&#945; in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments

Differential effects of peripheral and brain tumor necrosis factor on inflammation, sickness, emotional behavior and memory in mice

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Product

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The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments