Differential anxiety-like responses in NOD/ShiLtJ and C57BL/6J mice following experimental autoimmune encephalomyelitis induction and oral gavage

Abstract

Oral gavage is commonly used in pre-clinical drug evaluation, but is potentially aversive and may induce behavioral effects independent of compounds under investigation. This study examined the combined effects of repeated oral gavage and disease induction on anxiety-like behavior in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. The C57BL/6J and NOD/ShiLtJ EAE variants were exposed to sham-EAE induction or untreated control conditions, and either daily oral gavage or home cage conditions. Anxiety-like behavior was subsequently assessed in the elevated plus maze. C57BL/6J mice exhibited increased anxiety-like behavior, relative to NOD/ShiLtJ mice, in response to repeated gavage, whereas sham-EAE induction and repeated gavage were associated with increased anxiety-like behavior in NOD/ShiLtJ mice. Thus, exposure to the induction procedure and repeated gavage differentially altered subsequent anxiety-like behavior in the two EAE variants. Future pre-clinical studies should rely on prior evaluation of parameters of the experimental design using sham-EAE mice. Additionally, less aversive administration routes should be utilized wherever possible to ensure that procedures do not distort effects of the therapeutic under investigation.

Platelet Depletion is Effective in Ameliorating Anxiety-Like Behavior and Reducing the Pro-Inflammatory Environment in the Hippocampus in Murine Experimental Autoimmune Encephalomyelitis

“…C57BL/6J mice were obtained from the Animal Resource Centre (Perth, Australia) and housed under standard conditions at 23 °C and 12:12 light:dark cycle, on standard rodent chow (Barastoc, Rat and Mouse Feed, Ridley AgriProducts, Harristown, QLD, Australia) with food and water ad libitum [44]. All procedures were approved by the institutional Animal Ethics Committee and performed strictly in accordance with regulations set by the National Health and Medical Research Council of Australia.…”

“…All procedures were approved by the institutional Animal Ethics Committee and performed strictly in accordance with regulations set by the National Health and Medical Research Council of Australia. Only female mice aged 12–16 weeks were used in experimentation, due to the well-documented differences in disease incidence (3F:1M) and clinical sub-types (relapsing–remitting clinical course being more common in women) in MS [44]. MOG 33–55 -induced EAE was performed as previously described [45].…”

Autoimmune encephalomyelitis in NOD mice is not initially a progressive multiple sclerosis model

“…In addition, NOD/ShiLtJ mice were from stock bred at the La Trobe University. 32 Animal procedures were approved by the Institutional Animal Care and Use Committee at the La Trobe Institute, Australia. 23,32…”

“…16 Animals were injected intraperitoneally with 200 ng Bordetella pertussis toxin immediately and 24 h after each injection of antigen, as described previously. 16,32,33 These are the immunodominant myelin peptides associated with H-2A g7 reactivity in ABH mice. [33][34][35] Animals were scored as 0 = normal; 1 = limp tail; 2 = impaired righting reflex; 3 = hindlimb paresis; 4 = hindlimb paralysis; 5 = moribund (endpoint) as described previously.…”

“…16,33 Alternatively, animals (9-12 week) were immunized with 200 lg MOG residues 35-55 (MOG ) peptide emulsified in Freunds complete adjuvant supplemented with 4 mg/mL M. tuberculosis on day 0 and 350 ng intravenous B. pertussis toxin on day 0 and day 2. 23,32 These mice were scored as: 0 = no signs, 1 = limp tail, 2 = hindlimb weakness, 3 = hindlimb weakness with at least one paralyzed hindlimb, 4 = paralysis of both hindlimbs and weakness of one forelimb, 5 = moribund. 23 Animals were randomly assigned to treatments and the studies were scored blinded to induction agent.…”