Dataset Information

Dopamine System, NMDA Receptor and EGF Family Expressions in Brain Structures of Bl6 and 129Sv Strains Displaying Different Behavioral Adaptation.

ABSTRACT: C57BL/6NTac (Bl6) and 129S6/SvEvTac (129Sv) mice display different coping strategies in stressful conditions. Our aim was to evaluate biomarkers related to different adaptation strategies in the brain of male 129Sv and Bl6 mice. We focused on signaling pathways related to the dopamine (DA) system, N-methyl-D-aspartate (NMDA) receptor and epidermal growth factor (EGF) family, shown as the key players in behavioral adaptation. Mice from Bl6 and 129Sv lines were divided into either home cage controls (HCC group) or exposed to repeated motility testing and treated with saline for 11 days (RMT group). Distinct stress responses were reflected in severe body weight loss in 129Sv and the increased exploratory behavior in Bl6 mice. Besides that, amphetamine caused significantly stronger motor stimulation in Bl6. Together with the results from gene expression (particularly Maob), this study supports higher baseline activity of DA system in Bl6. Interestingly, the adaptation is reflected with opposite changes of DA markers in dorsal and ventral striatum. In forebrain, stress increased the gene expressions of Egf-Erbb1 and Nrg1/Nrg2-Erbb4 pathways more clearly in 129Sv, whereas the corresponding proteins were significantly elevated in Bl6. We suggest that not only inhibited activity of the DA system, but also reduced activity of EGF family and NMDA receptor signaling underlies higher susceptibility to stress in 129Sv. Altogether, this study underlines the better suitability of 129Sv for modelling neuropsychiatric disorders than Bl6.

SUBMITTER: Varul J

PROVIDER: S-EPMC8227283 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Mouse strains differ significantly in their behaviors and responses to pathogenic and pharmacological agents. This study seeks to characterize behavioral and metabolomic profiles of two widely used mouse lines, 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6), to acute administration of lipopolysaccharide (LPS). LPS caused a significant suppression of locomotor activity and a decline in body weight (BW) in both strains within 24 h. However, the BW loss was more pronounced in Bl6 than in 129Sv. Comparison of strains revealed clear differences between their metabolomic profiles. According to the general linear model analysis (GLM), the 1.5 h LPS challenge in Bl6 caused a decrease of propionylcarnitine (C3), glucogenic amino acids, and acetylornithine (Ac-Orn), whereas the response of 129Sv included decreased concentrations of short-chain acylcarnitines (SCACs), citrulline, and elevation of glycerophospholipid (PCaa C42:0) and sphingolipid [SM(OH)C16:1]. 24 h after LPS administration, robust alterations in lipid profile were observed in both strains. LPS treatment caused elevation of sphingolipids, phosphatidylcholine diacyls (PCaa) as well as a decrease in lysophosphatidylcholines (LysoPC). However, the number of elevated PCaa and sphingolipids was considerably higher in 129Sv. In addition to lipids, 24 h LPS challenge in Bl6 mice induced increased levels of kynurenine (KYN), putrescine and decreased levels of citrulline, hexoses, Ac-Orn, and PC acyl-alkyl (PCae 38:2) as well as severe BW loss. In contrast, the 24 h LPS challenge in 129Sv mice induced increased levels of KYN, long-chain acylcarnitines (LCACs) and decreased levels of citrulline as well as moderate BW loss. Altogether, our study revealed both similarities and differences in response to LPS in Bl6 and 129Sv strains. For major differences, Bl6 mice showed stronger reduction of BW 24 h after LPS treatment, accompanied by significantly reduced levels of hexoses, the ratio between LysoPC16:1/LysoPC16:0, and elevated levels of neuroprotective putrescine. In 129Sv mice, the BW loss was milder, accompanied by increased levels of hydroxylated LCACs, probably reflecting shifts in oxidative metabolism of fatty acids. One may suggest that LPS caused stronger hypometabolic state in the Bl6 mice than in the 129Sv strain. Altogether, this study confirms that Bl6 and 129Sv mice display vastly distinct adaptation capacities independent from the nature of stressful challenge.

Project description:The main goal of the study was to characterize the behavioral and metabolomic profiles of repeated administration (for 11 days) of d-amphetamine (AMPH, 3 mg/kg i. p.), indirect agonist of dopamine (DA), in widely used 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6) mouse strains. Acute administration of AMPH (acute AMPH) induced significantly stronger motor stimulation in Bl6. However, repeated administration of AMPH (repeated AMPH) caused stronger motor sensitization in 129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH induced an elevation of isoleucine and leucine, branched chain amino acids (BCAA), whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines [asymmetric dimethylarginine (ADMA), alpha-aminoadipic acid (alpha-AAA), kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in 129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:2, lysoPC a C20:4), phosphatidylcholine (PC) diacyls (PC aa C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4) and alkyl-acyls (PC ae C38:4, PC ae C40:4). However, repeated AMPH increased the levels of valine and isoleucine, long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1), PC diacyls (PC aa C38:4, PC aa C38:6, PC aa C42:6), PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:3) and sphingolipids [SM(OH)C22:1, SM C24:0] compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after repeated AMPH compared to saline in 129Sv. The established changes probably reflect a shift in energy metabolism toward lipid molecules in 129Sv because of reduced level of hexoses. Pooled data from both strains showed that the elevation of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral sensitization. Simultaneously a significant decline of hexoses, citrulline, ADMA, and kynurenine occurred. The reduced levels of kynurenine, ADMA, and citrulline likely reflect altered function of N-methyl-D-aspartate (NMDA) and NO systems caused by repeated AMPH. Altogether, 129Sv strain displays stronger sensitization toward AMPH and larger variance in metabolite levels than Bl6.

Dataset Information

Dopamine System, NMDA Receptor and EGF Family Expressions in Brain Structures of Bl6 and 129Sv Strains Displaying Different Behavioral Adaptation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets