Individual Differences in Behavioural Despair Predict Brain GSK-3beta Expression in Mice: The Power of a Modified Swim Test

Abstract

While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test with an additional session occurring on Day 5 following the initial exposure. Unexpectedly, floating behaviour and brain glycogen synthase kinase-3 beta (GSK-3beta) mRNA levels, a factor of synaptic plasticity as well as a marker of distress and depression, were increased during the additional swimming session that was prevented by imipramine. Observed increases of GSK-3beta mRNA in prefrontal cortex during delayed testing session correlated with individual parameters of behavioural despair that was not found in the classic Porsolt test. Repeated swim exposure was accompanied by a lower pGSK-3beta/GSK-3beta ratio. A replacement of the second or the final swim sessions with exposure to the context of testing resulted in increased GSK-3beta mRNA level similar to the effects of swimming, while exclusion of the second testing prevented these changes. Together, our findings implicate the activation of brain GSK-3beta expression in enhanced contextual conditioning of adverse memories, which is associated with an individual susceptibility to a depressive syndrome.

Longitudinal Association between n-3 Long-Chain Polyunsaturated Fatty Acid Intake and Depressive Symptoms: A Population-Based Cohort Study in Japan

“…Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two major n -3 long-chain polyunsaturated fatty acids ( n -3 LCPUFA) derived from fish and shellfish; they are essential for maintaining cellular membrane function and affect neurotransmitter release and modify receptor binding [ 15 ]. We should pay attention to the potential mechanisms that originate from models for depression with limitation when it comes to the comparability with human depression/depressive symptoms [ 16 , 17 ]; however, experimental studies have shown that these fatty acids have anti-inflammatory [ 18 ], antioxidative [ 19 ], neuroprotective [ 20 ], and neurogenesis effects [ 21 ]. These factors may also be important in protecting against depression and inflammation-related diseases [ 22 ].…”

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

“…The Porsolt test (PT) is a validated test evaluating depressive-like behaviors and coping strategies [ 79 , 80 ]. In the present study, we assessed depressive-like behavior with PT since depression is frequently identified in elderly individuals, also at subthreshold levels and with a high prevalence in the community-dwelling elderly individuals [ 81 , 82 ].…”

Gsk3β aggravates the depression symptoms in chronic stress mouse model

“…Reports have suggested that GSK-3β might have a broader function in regulation of the behavioral domain. However, there have been contradictory results concerning GSK-3β expression and activity in some studies of depressive models [10][11][12][13]. Therefore, a depressive mice model was established to study the role of GSK-3β and related signalling pathways.…”