Effect of interferon-α on tyrosine hydroxylase and catecholamine levels in the brain of rats

Kumai, Toshio; Tateishi, Tetsuya; Tanaka, Michitaka; Watanabé, Masanosuké; Shimizu, Hiromi; Kobayashi, Shigeru

doi:10.1016/s0024-3205(00)00660-3

Cited by 39 publications

(33 citation statements)

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“…; Kumai et al, 2000;Shuto et al, 1997;Sunami et al, 2000). Our results are consistent with these observations and suggest that increased basal ganglia resting state glucose metabolism in IFN-a-treated patients may be indicative of altered dopaminergic activity, as is seen in patients with Parkinson's disease (PD).…”

supporting

confidence: 88%

Basal Ganglia Hypermetabolism and Symptoms of Fatigue during Interferon-α Therapy

Capuron

Pagnoni

Demetrashvili

et al. 2007

Neuropsychopharmacol

209

175

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Interferon (IFN)-a is a cytokine of the innate immune response that is well known for inducing behavioral alterations and has been used to study effects of cytokines on the nervous system. Limited data, however, are available on the sites of action of IFN-a within the brain and their relationship with specific IFN-a-induced symptoms. Using a longitudinal design, whole-brain metabolic activity as assessed by fluorine-18-labeled fluorodeoxyglucose uptake and positron emission tomography was examined before and 4 weeks after IFN-a administration in patients with malignant melanoma. Changes in metabolic activity in relevant brain regions were then correlated with IFN-a-induced behavioral changes. IFN-a administration was associated with widespread bilateral increases in glucose metabolism in subcortical regions including the basal ganglia and cerebellum. Decreases in dorsal prefrontal cortex glucose metabolism were also observed. Prominent IFN-a-induced behavioral changes included lassitude, inability to feel, and fatigue. Correlational analyses revealed that self-reported fatigue (specifically as assessed by the 'energy' subscale of the Visual Analog Scale of Fatigue) was associated with increased glucose metabolism in the left nucleus accumbens and putamen. These data indicate that IFN-a as well as other cytokines of the innate immune response may target basal ganglia nuclei, thereby contributing to fatigue-related symptoms in medically ill patients.

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supporting

confidence: 88%

Basal Ganglia Hypermetabolism and Symptoms of Fatigue during Interferon-α Therapy

Capuron

Pagnoni

Demetrashvili

et al. 2007

Neuropsychopharmacol

209

175

View full text Add to dashboard Cite

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“…Kumai et al reported that 7-day s.c. injection of 300 000 IU/kg IFN-α per day raised NE and DA levels in the cerebral cortex, hypothalamus and medulla oblongata. 25 However, such changes were not observed after 4-and 14-day treatment in the present study, suggesting that increased NE and DA levels represent subacute and transient effects of IFN-α therapy.…”

Section: Discussioncontrasting

confidence: 80%

“…11,[22][23][24][25][26][27] Divergent results might be attributable to methodological differences. To the best of our knowledge, this report is the first to address both the dose-dependent and the temporal effects of peripherally administered IFN-α on various brain regions.…”

Section: Discussionmentioning

confidence: 99%

Chronic intraperitoneal injection of interferon‐α reduces serotonin levels in various regions of rat brain, but does not change levels of serotonin transporter mRNA, nitrite or nitrate

Sato¹,

Suzuki²,

Yokoyama³

et al. 2006

Psychiatry Clin Neurosci

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Interferon-α therapy is associated with a high rate of depression, but the pathophysiological mechanisms remain unclear. The purpose of the present study was to investigate the effects of i.p. administered interferon-α on monoaminergic neurotransmission in the brain. The levels of monoamines and associated metabolites were measured in various regions of the rat brain using a high-performance liquid chromatography-electrochemical detection system. The serotonin transporter mRNA levels were also measured using in situ hybridization. After 1 day, dopamine turnover was diminished in the cortex. Norepinephrine turnover was decreased in most regions tested after 4 days. However, these changes were transient. After 14 days, serotonin turnover was increased in the frontal cortex and hippocampus in rats given a dose of 20 000 IU/kg; in the frontal cortex, hippocampus, amygdala, thalamus, hypothalamus and brainstem in those on 200 000 IU/kg; and in the thalamus and hypothalamus in those on 2 000 000 IU/kg (all P < 0.05). However, 14-day treatment did not significantly change serotonin transporter mRNA levels. Next, the question of whether interferon-α affects monoamine levels via induction of nitric oxide (NO), was investigated. However, there were no changes in either NO 2 -or NO 3 -, as markers of NO production, in any brain regions after 14-day treatment. These results suggest that chronic peripheral administration of interferon-α induces metabolic changes in the central serotonin system. Further investigation is needed to determine exactly how this cytokine affects the central serotonin system and to assess whether a central serotonin abnormality is involved in interferon-induced depression.

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“…Initial evidence that inflammation can affect brain DA originates from neurochemical and behavioral studies in rodents administered acute or subchronic IFN-α that measured DA and/or DA metabolites in concert with depressive behaviors and changes in locomotor activity (Kamata et al, 2000;Kitagami et al, 2003;Kumai et al, 2000;Sato et al, 2006;Shuto et al, 1997). Some studies reported increases (Kumai et al, 2000;Sato et al, 2006), whereas others have reported decreases (Kamata et al, 2000;Kitagami et al, 2003;Shuto et al, 1997) in brain DA and/or metabolites following acute or subchronic IFN-α administration.…”

Section: Biochemical and Behavioral Studies In Laboratory Animalsmentioning

confidence: 99%

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Felger

Treadway

2016

Neuropsychopharmacol

319

237

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Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.

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Effect of interferon-α on tyrosine hydroxylase and catecholamine levels in the brain of rats

Cited by 39 publications

References 0 publications

Basal Ganglia Hypermetabolism and Symptoms of Fatigue during Interferon-α Therapy

Basal Ganglia Hypermetabolism and Symptoms of Fatigue during Interferon-α Therapy

Chronic intraperitoneal injection of interferon‐α reduces serotonin levels in various regions of rat brain, but does not change levels of serotonin transporter mRNA, nitrite or nitrate

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

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