Amprolium exposure alters mice behavior and metabolism in vivo

Abstract

Background Thiamine deficiency ( TD ) models have been developed, mainly using the thiamine analog pyrithiamine. Other analogs have not been used in rodents. We aimed to evaluate the effects and mechanisms of intraperitoneal (ip) amprolium‐induced TD in mice. We also evaluated the associated pathogenesis using antioxidant and anti‐inflammatory compounds (Trolox, dimethyl sulfoxide). Methods Male mice were separated into two groups, one receiving a standard diet (control animals), and the other a TD diet (deficient groups) for 20 days. Control mice were further subdivided into three groups receiving daily ip injections of saline (NaCl 0.9%; Cont group), Tolox (Tr group) or dimethyl sulfoxide ( DMSO ; Dmso group). The three TD groups received amprolium (Amp group), amprolium and Trolox (Amp+Tr group), or amprolium and DMSO (Amp+Dmso group). The animals were subjected to behavioral tests and then euthanized. The brain and viscera were analyzed. Results Amprolium exposure induced weight loss with hyporexia, reduced the behavioral parameters (locomotion, exploratory activity, and motor coordination), and induced changes in the brain (lower cortical cell viability) and liver (steatosis). Trolox co‐treatment partially improved these conditions, but to a lesser extent than DMSO . Conclusions Amprolium‐induced TD may be an interesting model, allowing the deficiency to develop more slowly and to a lesser extent. Amprolium exposure also seems to involve oxidative stress and inflammation, suggested as the main mechanisms of cell dysfunction in TD .

Thiamine Deficiency Causes Long-Lasting Neurobehavioral Deficits in Mice

“…Adult male Swiss mice, when treated with thiamine antagonist pyrithiamine in conjunction with a TD diet, showed a reduction in locomotor activity during the course of dietary treatment [ 48 ]. Another thiamine antagonist, amprolium, also decreased the locomotor activity of mice when either treated alone with a high dose and extended period [ 49 ] or combined with a TD diet [ 50 ]. In our model, we only used a TD diet without adding a thiamine antagonist.…”

ERK1/2 modulation in the central nervous system of male and female thiamine-deficient mice with amprolium

“…22 The sample size was chosen based on pilot studies and previous experience. 12 Nest building material was provided, and all cages contained enrichment such as a tunnel. The animals were always handled with sterile gloves, and the material for nests and bedding (autoclaved shavings) was monitored daily and changed every three days.…”

“…The deficient groups received thiamine-deficient AIN-93TD chow (0.0 mg thiamine hydrochloride per kilogram of feed; PRAG Soluc¸ões Biocieˆncias) during periods of deficiency induction. 5,6,12 The constituents of the thiamine-deficient diet were identical to those of the standard diet, except for a lack of vitamins.…”

“…10 Recent relevant studies have demonstrated significant behavioral and metabolic disorders in thiamine-deficient mice with amprolium. 11,12 Furthermore, there has recently been a significant movement to include both sexes in animal studies. 13 However, biological differences between males and females occur in several respects, which may restrict the use of both sexes in research.…”

The Effects of Genetic Mutations and Drugs on the Activity of the Thiamine Transporter, SLC19A2

“…Approximately 60 SLC19A2 variants have been associated with TRMA (Supplemental Table 1 ) ( 5 , 9 ), yet few have been functionally characterized to date. A mouse model of dietary thiamine deficiency (TD) has been used extensively to evaluate the effects of systemic thiamine depletion on neurological functions ( 10 ). However, there are no studies employing the TD model (or any in vivo system) to evaluate the impact of systemic thiamine depletion on erythropoiesis and megaloblastic anemia.…”