Effects of long-term infliximab and tocilizumab treatment on anxiety-like behavior and cognitive function in naive rats.
Animals
Antibodies, Monoclonal, Humanized
/ pharmacology
Anxiety
/ drug therapy
Behavior, Animal
/ drug effects
Brain
/ drug effects
Brain-Derived Neurotrophic Factor
/ metabolism
Cognition
/ drug effects
Gene Expression Regulation
/ drug effects
Infliximab
/ pharmacology
Interleukin-6
/ antagonists & inhibitors
Rats
Treatment Outcome
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
Anxiety
BDNF
Infliximab
Memory
Tocilizumab
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
03
05
2021
accepted:
16
09
2021
revised:
16
09
2021
pubmed:
28
9
2021
medline:
5
3
2022
entrez:
27
9
2021
Statut:
ppublish
Résumé
Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function. Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8 weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment. Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain.
Sections du résumé
BACKGROUND
BACKGROUND
Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function.
METHODS
METHODS
Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8 weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
RESULTS
RESULTS
Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment.
CONCLUSIONS
CONCLUSIONS
Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain.
Identifiants
pubmed: 34569017
doi: 10.1007/s43440-021-00328-x
pii: 10.1007/s43440-021-00328-x
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Bdnf protein, rat
0
Brain-Derived Neurotrophic Factor
0
Il6 protein, rat
0
Interleukin-6
0
Tumor Necrosis Factor-alpha
0
Infliximab
B72HH48FLU
tocilizumab
I031V2H011
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
84-95Informations de copyright
© 2021. Maj Institute of Pharmacology Polish Academy of Sciences.
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