Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions
Increasing evidence demonstrates that inflammatory cytokines—such as tumor necrosis factor (TNF)—are produced at low levels in the brain under physiological conditions and may be crucial for synaptic plasticity, neurogenesis, learning and memory. Here, we examined the effects of developmental TNF de...
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MDPI AG
2021-03-01
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| author | Leda Mygind Marianne Skov-Skov Bergh Vivien Tejsi Ramanan Vaitheeswaran Kate L. Lambertsen Bente Finsen Athanasios Metaxas |
| author_facet | Leda Mygind Marianne Skov-Skov Bergh Vivien Tejsi Ramanan Vaitheeswaran Kate L. Lambertsen Bente Finsen Athanasios Metaxas |
| author_sort | Leda Mygind |
| collection | DOAJ |
| description | Increasing evidence demonstrates that inflammatory cytokines—such as tumor necrosis factor (TNF)—are produced at low levels in the brain under physiological conditions and may be crucial for synaptic plasticity, neurogenesis, learning and memory. Here, we examined the effects of developmental TNF deletion on spatial learning and memory using 11–13-month-old TNF knockout (KO) and C57BL6/J wild-type (WT) mice. The animals were tested in the Barnes maze (BM) arena under baseline conditions and 48 h following an injection of the endotoxin lipopolysaccharide (LPS), which was administered at a dose of 0.5 mg/kg. Vehicle-treated KO mice were impaired compared to WT mice during the acquisition and memory-probing phases of the BM test. No behavioral differences were observed between WT and TNF-KO mice after LPS treatment. Moreover, there were no differences in the hippocampal content of glutamate and noradrenaline between groups. The effects of TNF deletion on spatial learning and memory were observed in male, but not female mice, which were not different compared to WT mice under baseline conditions. These results indicate that TNF is required for spatial learning and memory in male mice under physiological, non-inflammatory conditions, however not following the administration of LPS. Inflammatory signalling can thereby modulate spatial cognition in male subjects, highlighting the importance of sex- and probably age-stratified analysis when examining the role of TNF in the brain. |
| first_indexed | 2024-03-10T13:24:25Z |
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| language | English |
| last_indexed | 2024-03-10T13:24:25Z |
| publishDate | 2021-03-01 |
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| series | Cells |
| spelling | doaj.art-a8d01e125f29433c944b38f535f43f072023-11-21T09:48:59ZengMDPI AGCells2073-44092021-03-0110360810.3390/cells10030608Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged ConditionsLeda Mygind0Marianne Skov-Skov Bergh1Vivien Tejsi2Ramanan Vaitheeswaran3Kate L. Lambertsen4Bente Finsen5Athanasios Metaxas6Institute of Molecular Medicine, Department of Neurobiology, University of Southern Denmark, J.B. Winsløws Vej 25, DK-5000 Odense C, DenmarkDepartment of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Loviseberggata, 60456 Oslo, NorwayInstitute of Molecular Medicine, Department of Neurobiology, University of Southern Denmark, J.B. Winsløws Vej 25, DK-5000 Odense C, DenmarkInstitute of Molecular Medicine, Department of Neurobiology, University of Southern Denmark, J.B. Winsløws Vej 25, DK-5000 Odense C, DenmarkInstitute of Molecular Medicine, Department of Neurobiology, University of Southern Denmark, J.B. Winsløws Vej 25, DK-5000 Odense C, DenmarkInstitute of Molecular Medicine, Department of Neurobiology, University of Southern Denmark, J.B. Winsløws Vej 25, DK-5000 Odense C, DenmarkInstitute of Molecular Medicine, Department of Neurobiology, University of Southern Denmark, J.B. Winsløws Vej 25, DK-5000 Odense C, DenmarkIncreasing evidence demonstrates that inflammatory cytokines—such as tumor necrosis factor (TNF)—are produced at low levels in the brain under physiological conditions and may be crucial for synaptic plasticity, neurogenesis, learning and memory. Here, we examined the effects of developmental TNF deletion on spatial learning and memory using 11–13-month-old TNF knockout (KO) and C57BL6/J wild-type (WT) mice. The animals were tested in the Barnes maze (BM) arena under baseline conditions and 48 h following an injection of the endotoxin lipopolysaccharide (LPS), which was administered at a dose of 0.5 mg/kg. Vehicle-treated KO mice were impaired compared to WT mice during the acquisition and memory-probing phases of the BM test. No behavioral differences were observed between WT and TNF-KO mice after LPS treatment. Moreover, there were no differences in the hippocampal content of glutamate and noradrenaline between groups. The effects of TNF deletion on spatial learning and memory were observed in male, but not female mice, which were not different compared to WT mice under baseline conditions. These results indicate that TNF is required for spatial learning and memory in male mice under physiological, non-inflammatory conditions, however not following the administration of LPS. Inflammatory signalling can thereby modulate spatial cognition in male subjects, highlighting the importance of sex- and probably age-stratified analysis when examining the role of TNF in the brain.https://www.mdpi.com/2073-4409/10/3/608TNFLPSinflammationsickness behavioragingcognition |
| spellingShingle | Leda Mygind Marianne Skov-Skov Bergh Vivien Tejsi Ramanan Vaitheeswaran Kate L. Lambertsen Bente Finsen Athanasios Metaxas Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions Cells TNF LPS inflammation sickness behavior aging cognition |
| title | Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions |
| title_full | Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions |
| title_fullStr | Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions |
| title_full_unstemmed | Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions |
| title_short | Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions |
| title_sort | tumor necrosis factor tnf is required for spatial learning and memory in male mice under physiological but not immune challenged conditions |
| topic | TNF LPS inflammation sickness behavior aging cognition |
| url | https://www.mdpi.com/2073-4409/10/3/608 |
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