TY - JOUR
T1 - Enhanced conditioning of adverse memories in the mouse modified swim test is associated with neuroinflammatory changes - Effects that are susceptible to antidepressants
AU - Pavlov, D.
AU - Gorlova, A.
AU - Bettendorff, L.
AU - Kalueff, A.A.
AU - Umriukhin, A.
AU - Proshin, A.
AU - Lysko, A.
AU - Landgraf, R.
AU - Anthony, D.C.
AU - Strekalova, T.
N1 - Funding Information:
The authors' work reported here was supported by the Horizon 2020 Research and Innovation Program under Grant No. 728018 (Eat2beNICE, to KPL and TS), (EURON mobility grant 2019 to TS, DP and LB), and ?5?100? Russian Research Excellence program (to TS and KPL). LB is Research Director of the F.R.S.-FNRS (Belgium).
Funding Information:
The authors' work reported here was supported by the Horizon 2020 Research and Innovation Program under Grant No. 728018 (Eat2beNICE, to KPL and TS), (EURON mobility grant 2019 to TS, DP and LB), and “5–100” Russian Research Excellence program (to TS and KPL). LB is Research Director of the F.R.S.-FNRS (Belgium).
Publisher Copyright:
© 2020 The Authors
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Deficient learning and memory are well-established pathophysiologic features of depression, however, mechanisms of the enhanced learning of aversive experiences associated with this disorder are poorly understood. Currently, neurobiological mechanisms of enhanced retention of aversive memories during depression, and, in particular, their relation to neuroinflammation are unclear. As the association between major depressive disorder and inflammation has been recognized for some time, we aimed to address whether neuroinflammatory changes are involved in enhanced learning of adversity in a depressive state. To study this question, we used a recently described mouse model of enhanced contextual conditioning of aversive memories, the modified forced swim model (modFST). In this model, the classic two-day forced swim is followed by an additional delayed session on Day 5, where increased floating behaviour and upregulated glycogen synthase kinase-3 (GSK-3) are context-dependent. Here, increased time spent floating on Day 5, a parameter of enhanced learning of the adverse context, was accompanied by hypercorticosteronemia, increased gene expression of GSK-3 alpha, GSK-3 beta, c-Fos, cyclooxygenase-1 (COX-1) and pro-inflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), and elevated concentrations of protein carbonyl, a marker of oxidative stress, in the prefrontal cortex and hippocampus. There were significant correlations between cytokine levels and GSK-3 beta gene expression. Two-week administration of compounds with antidepressant properties, imipramine (7 mg/kg/day) or thiamine (vitamin B1; 200 mg/kg/day) ameliorated most of the modFST-induced changes. Thus, enhanced learning of adverse memories is associated with pro-inflammatory changes that should be considered for optimizing pharmacotherapy of depression associated with enhanced learning of aversive memories.
AB - Deficient learning and memory are well-established pathophysiologic features of depression, however, mechanisms of the enhanced learning of aversive experiences associated with this disorder are poorly understood. Currently, neurobiological mechanisms of enhanced retention of aversive memories during depression, and, in particular, their relation to neuroinflammation are unclear. As the association between major depressive disorder and inflammation has been recognized for some time, we aimed to address whether neuroinflammatory changes are involved in enhanced learning of adversity in a depressive state. To study this question, we used a recently described mouse model of enhanced contextual conditioning of aversive memories, the modified forced swim model (modFST). In this model, the classic two-day forced swim is followed by an additional delayed session on Day 5, where increased floating behaviour and upregulated glycogen synthase kinase-3 (GSK-3) are context-dependent. Here, increased time spent floating on Day 5, a parameter of enhanced learning of the adverse context, was accompanied by hypercorticosteronemia, increased gene expression of GSK-3 alpha, GSK-3 beta, c-Fos, cyclooxygenase-1 (COX-1) and pro-inflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), and elevated concentrations of protein carbonyl, a marker of oxidative stress, in the prefrontal cortex and hippocampus. There were significant correlations between cytokine levels and GSK-3 beta gene expression. Two-week administration of compounds with antidepressant properties, imipramine (7 mg/kg/day) or thiamine (vitamin B1; 200 mg/kg/day) ameliorated most of the modFST-induced changes. Thus, enhanced learning of adverse memories is associated with pro-inflammatory changes that should be considered for optimizing pharmacotherapy of depression associated with enhanced learning of aversive memories.
KW - brain
KW - cytokines
KW - depression
KW - enhanced learning of adverse memories
KW - glutamate release
KW - glycogen synthase kinase-3 (gsk-3)
KW - glycogen-synthase kinase-3
KW - inflammatory markers
KW - major depression
KW - mice
KW - model
KW - oxidative stress
KW - pathophysiology
KW - pathways
KW - posttraumatic-stress-disorder
KW - tnf
KW - PATHWAYS
KW - Oxidative stress
KW - POSTTRAUMATIC-STRESS-DISORDER
KW - GLUTAMATE RELEASE
KW - TNF
KW - Enhanced learning of adverse memories
KW - BRAIN
KW - DEPRESSION
KW - Cytokines
KW - GLYCOGEN-SYNTHASE KINASE-3
KW - MODEL
KW - INFLAMMATORY MARKERS
KW - PATHOPHYSIOLOGY
KW - Major depression
KW - Glycogen synthase kinase-3 (GSK-3)
KW - Mice
U2 - 10.1016/j.nlm.2020.107227
DO - 10.1016/j.nlm.2020.107227
M3 - Article
C2 - 32325189
SN - 1074-7427
VL - 172
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
M1 - 107227
ER -