Repeated Injections of Interferon-α A/D in Balb/c Mice: Behavioral Effects

Dunn, Ariel; Crnic, Linda S.

doi:10.1006/brbi.1993.1011

Cited by 49 publications

(16 citation statements)

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“…In contrast to previous reports (Corssmit et al, 1996;Dunn and Crnic, 1993;Gisslinger et al, 1993;Menzies et al, 1996), there were no significant changes in food intake, motor activities, or plasma glucocorticoid levels, all of which have been (Cameron and Gould, 1994;Gould et al, 1997;Mattson et al, 2003;van Praag et al, 1999), in the rats given IFN-a for a week. The differences in the results may be explained by differences in the doses of IFN-a used; we used much lower doses than that used in a previous study reporting these effects (Dunn and Crnic, 1993), as these adverse events associated with IFN-a have been shown to be dose-dependent (Dunn and Crnic, 1993;Kirkwood et al, 1985). Consistent with the results of previous studies in which interferons were shown to stimulate the production of inflammatory cytokines in peripheral immunocytes (Haq and Maca, 1986;Sissolak et al, 1992;Taylor and Grossberg, 1998), IFN-a increased IL-1b immunoreactivity in hippocampal astrocytes, and the amount of the active form of IL-1b protein in the hippocampus, as shown by Western blotting.…”

Section: Interferon Suppresses Neurogenesis N Kaneko Et Alcontrasting

confidence: 99%

Suppression of Cell Proliferation by Interferon-Alpha through Interleukin-1 Production in Adult Rat Dentate Gyrus

Kaneko

Kudo

Mabuchi

et al. 2006

Neuropsychopharmacol

136

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The therapeutic use of interferon-alpha (IFN-a), a proinflammatory cytokine, is known to cause various neuropsychiatric adverse effects. In particular, depression occurs in 30-45% of patients, frequently interrupting treatment. IFN-a-treated animals also show depression-like behaviors. However, mechanisms underlying the depression caused by IFN-a remain to be defined. Recently, a decrease in adult hippocampal neurogenesis was revealed as a possible neuropathological mechanism of depression. Therefore, we investigated the effect of subchronic IFN-a treatment on neurogenesis in the adult rat dentate gyrus (DG). Immediately after the administration of IFN-a for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later. Also, an increase in the level of interleukin-1beta (IL-1b), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-a. Furthermore, coadministration of an IL-1 receptor antagonist completely blocked the IFN-a-induced suppression of the cell-proliferative activity in the DG. Our results indicate that IFN-a suppresses neurogenesis in the DG, and that IL-1b plays an essential role in the suppression. The decreased cell proliferation caused by IFN-a-induced IL-1b may be responsible, at least in part, for IFN-a-induced depression.

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Section: Interferon Suppresses Neurogenesis N Kaneko Et Alcontrasting

confidence: 99%

Suppression of Cell Proliferation by Interferon-Alpha through Interleukin-1 Production in Adult Rat Dentate Gyrus

Kaneko

Kudo

Mabuchi

et al. 2006

Neuropsychopharmacol

136

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“…Unlike paralysis in experimental autoimmune encephalomyelitis (EAE) 2 or experimental autoimmune myasthenia gravis (EAMG), 4 muscular weakness in this type of myopathy cannot be determined by an obvious visual score. Strength-assessing methods which have been used in other experimental models, such as the length of time an animal can hang from a cage top or swim in a tank, 4,8,14 are not very quantitative and can be very hard on the animal. Force transduction strength testing is noninvasive, and the same animal can be tested frequently without great distress.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous myopathy in the SJL/J mouse: Pathology and strength loss

et al. 1997

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“…One mechanism by which IFN-alpha is believed to induce behavioural symptoms is through alteration of dopamine neurotransmission and basal ganglia function. For example, animal studies have shown that chronic IFN-alpha administration induces a robust depression in motor activity and reduces dopamine concentrations in the mouse brain (Dunn and Crnic, 1993;Shuto et al, 1997). Moreover, Parkinson-like motor symptoms have been described in patients treated with IFNalpha for chronic hepatitis C, and levodopa, an intermediate in dopamine biosynthesis, has been shown to significantly ameliorate IFN-alpha-induced akathisia, a symptom of "inner" motor restlessness often associated with dopamine blockade by antipsychotic medications (Sunami et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C

Majer

Welberg

Capuron

et al. 2008

Brain, Behavior, and Immunity

105

102

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Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behavior. Previous studies suggest that altered basal ganglia function may contribute to IFN-alpha-induced neuropsychological and behavioural changes. To further examine IFN-alpha effects on neuropsychological functions related to basal ganglia (as well as other brain regions), and explore the relationship between altered neuropsychological function and IFN-alphainduced depression and fatigue, a selected subset of the Cambridge Neuropsychological Test Automated Battery was administered to 32 hepatitis C patients at baseline (Visit 1) and following 12 weeks (Visit 2) of either no treatment (n=12) or treatment with IFN-alpha plus ribavirin (n=20). Symptoms of depression and fatigue were assessed using the Montgomery-Asberg Depression Rating Scale and the Multi-Dimensional Fatigue Inventory. Compared to control subjects, patients treated with IFN-alpha/ribavirin exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task and slower response times in the rapid visual information processing task, a task of sustained attention. Decreased motor speed on the five-choice movement segments of the reaction time task were in turn correlated with increased symptoms of depression and fatigue (R=0.47, p<.05 and R=0.48, p<.05, respectively). IFN-alpha/ ribavirin treatment had no effects on executive function, decision time in the reaction time task, or target detection accuracy in the sustained attention task. Motor slowing and its correlation with psychiatric symptoms suggest that altered basal ganglia function may contribute to the pathogenesis of IFN-alpha-induced behavioural changes.

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Repeated Injections of Interferon-α A/D in Balb/c Mice: Behavioral Effects

Cited by 49 publications

References 0 publications

Suppression of Cell Proliferation by Interferon-Alpha through Interleukin-1 Production in Adult Rat Dentate Gyrus

Suppression of Cell Proliferation by Interferon-Alpha through Interleukin-1 Production in Adult Rat Dentate Gyrus

Spontaneous myopathy in the SJL/J mouse: Pathology and strength loss

IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C

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