Alteration of hippocampal Egr3, GABA A receptors, Il-1ß, Il6 and Ccl3 expression in audiogenic tremor mice after seizure.

Neuroinflammation plays a protective role in the brain; however, in neurological diseases such as epilepsy, overactivated neuroinflammation, along with overexpression of inflammatory mediators, can cause neuronal tissue damage, which can trigger seizures due to loss of ionic or neurotransmitter homeostasis. Therefore, we aimed to evaluate mRNA expression levels of proinflammatory cytokines, early growth response factor 3 (Egr3), and GABA A receptors in the hippocampus of naive audiogenic mutant tremor mice, and stimulated tremor mice after a seizure. Gene expression of Il-1ß, Il-6, Tnf-α, Ccl2, Ccl3, Egr3, Gabra1, and Gabra4 from hippocampal samples of naive and stimulated tremor mice were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Relative to resistant mice, Ccl3 gene expression was increased and Il6 was decreased in the hippocampus of naïve tremor mice. Thirty minutes after a seizure, Ccl3 and Il-1ß mRNA expression were decreased (p < 0.0001; p = 0.0034, respectively) while Il6 was increased (p = 0.0052) in stimulated tremor mice, relative to naïve animals. In addition, Egr3, Gabra1, and Gabra4 mRNA expression was decreased in the hippocampus of naive tremor mice, relative to resistant mice, which increased 30 minutes after a seizure (p = 0.0496; p = 0.0447, and p = 0.0011, respectively), relative to naïve animals. In conclusion, overexpression of Ccl3 in the hippocampus of naive tremor mice, followed by downregulation soon after seizure in stimulated tremor mice, could be involved in changes in the blood-brain barrier (BBB) permeability in epilepsy. Il-1ß may be involved in hippocampal downregulation of GABA A receptors of naive tremor mice, characterizing an important mechanism in audiogenic seizures triggering. Hippocampal alterations of proinflammatory cytokines, Egr3, and GABA A receptors in tremor mice reinforce them as an alternative tool to modeling temporal lobe epilepsy.

Behavioral and neurochemical characterization of the spontaneous mutation tremor, a new mouse model of audiogenic seizures.

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss-Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21 cM) and D14Mit115 (38.21 cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p = .0012), serotonin (5HT; p = .0083), 5-hydroxyindoleacetic acid (5-HIAA; p = .0032), γ-amino butyric acid (GABA; p = .0123), glutamate (p = .0217) and aspartate (p = .0124). In opposition, the content of glycine (p = .0168) and the vanillylmandelic acid (VMA)/NOR ratio (p = .032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.

Administration of meloxicam to improve the welfare of mice in research: a systematic review (2000 - 2020).

Although laboratory animals experience pain as a necessary component of the objectives of experimental protocols, the level of pain should be minimized through use of an adequate analgesic regimen. The non-steroidal anti-inflammatory drug meloxicam may be beneficial in alleviating post-operative pain in mice, although no regimen has been demonstrated as universally efficacious owing to differences in experimental protocols, strain, sex, and incomplete descriptions of methodology in the literature. The aim of this systematic literature review was to identify potential applications of meloxicam for pain management in experimental mice and to evaluate the general quality of study design. Searches of MEDLINE, Scopus and CAB Direct databases elicited 94 articles published between January 2000 and April 2020 that focused on the analgesic efficacy of meloxicam in the management of momentary or persistent pain in mice. The extracted data showed that most articles were deficient in descriptions of housing, husbandry, group size calculation and humane endpoint criteria, while few described adverse effects of the drug. A wide range of dosages of meloxicam was identified with analgesic efficiencies that varied considerably according to the different models or procedures studied. It was impossible to correlate the extracted data into a single meta-analysis because of the differences in experimental protocols and strains employed, the low representation of female mice in the studies, and incomplete descriptions of the methodology applied. We conclude that meloxicam has potential application for pain management in mice but that the dosage must be adjusted carefully according to the experimental procedures. Moreover, authors must take more care in designing their studies and in describing the methodology employed.

Behavioral and neurochemical characterization of the spontaneous mutation tremor, a new mouse model of audiogenic seizures

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss–Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21cM) and D14Mit115 (38.21cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p=.0012), serotonin (5HT; p=.0083), 5-hydroxyindoleacetic acid (5-HIAA; p=.0032), gama-amino butyric acid (GABA; p=.0123), glutamate (p=.0217) and aspartate (p=.0124). In opposition, the content of glycine (p=.0168) and the vanillylmandelic acid (VMA)/NOR ratio (p=.032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.

Behavioral and neurochemical characterization of the spontaneous mutation tremor, a new mouse model of audiogenic seizures

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss–Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21cM) and D14Mit115 (38.21cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p=.0012), serotonin (5HT; p=.0083), 5-hydroxyindoleacetic acid (5-HIAA; p=.0032), gama-amino butyric acid (GABA; p=.0123), glutamate (p=.0217) and aspartate (p=.0124). In opposition, the content of glycine (p=.0168) and the vanillylmandelic acid (VMA)/NOR ratio (p=.032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.