Anemia of cancer (AC) may contribute to cancer-related fatigue and impair quality of life. Improved understanding of the pathogenesis of AC could facilitate better treatment, but animal models to study AC are lacking. We characterized four syngeneic C57BL/6 mouse cancers that cause AC. Mice with two different rapidly-growing metastatic lung cancers developed the characteristic findings of anemia of inflammation (AI), with dramatically different degrees of anemia. Mice with rapidly-growing metastatic melanoma also developed a severe anemia by 14 days, with hematologic and inflammatory parameters similar to AI. Mice with a slow-growing peritoneal ovarian cancer developed an iron-deficiency anemia, likely secondary to chronically impaired nutrition and bleeding into the peritoneal cavity. Of the four models, hepcidin mRNA levels were increased only in the milder lung cancer model. Unlike in our model of systemic inflammation induced by heat-killed Brucella abortus, ablation of hepcidin in the ovarian cancer and the milder lung cancer mouse models did not affect the severity of anemia. Hepcidin-independent mechanisms play an important role in these murine models of AC.
Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino--(methylsulfonyl)butanamide hydrochloride abolished ECTinduced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.
Because hepcidin overproduction mimics anemia of inflammation and absence of hepcidin protects against the acute hypoferremia seen in response to inflammation, hepcidin is presumed to be necessary for the development of anemia of inflammation (AI, anemia of chronic disease). However no independent studies have tested this hypothesis. Using two mouse models of anemia of inflammation and hepcidin deficient mice, we sought to determine whether hepcidin is necessary for the development of anemia of inflammation. Hepcidin knockout mice maintained on a standard iron diet were largely protected against AI. However, these mice have severe iron overload prior to the onset of inflammation, which may protect them against AI. We therefore sought to prevent the development of iron overload prior to the onset of inflammation by restricting dietary iron immediately after weaning. Hepcidin knockout mice without baseline iron overload developed anemia as severe as wild type mice and this anemia was iron restricted. Therefore, hepcidin is not necessary for the development of anemia in some inflammatory diseases. Hepcidin antagonists may not be effective in treating some patients with AI.
Because hepcidin overproduction mimics anemia of inflammation and absence of hepcidin protects against the acute hypoferremia seen in response to inflammation, hepcidin is presumed to be necessary for the development of anemia of inflammation (AI, anemia of chronic disease). However no independent studies have tested this hypothesis. Using two mouse models of anemia of inflammation and hepcidin deficient mice, we sought to determine whether hepcidin is necessary for the development of anemia of inflammation. Hepcidin knockout mice maintained on a standard iron diet were largely protected against AI. However, these mice have severe iron overload prior to the onset of inflammation, which may protect them against AI. We therefore sought to prevent the development of iron overload prior to the onset of inflammation by restricting dietary iron immediately after weaning. Hepcidin knockout mice without baseline iron overload developed anemia as severe as wild type mice and this anemia was iron restricted. Therefore, hepcidin is not necessary for the development of anemia in some inflammatory diseases. Hepcidin antagonists may not be effective in treating some patients with AI.
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