Search bioRxiv⌕ Search

Biology subjects

Torok, C.

Publications and source records attributed to Torok, C..

3 recordsLinked to original sources

MK2 deficiency decreases mortality during the inflammatory phase after myocardial infarction in mice

BackgroundAltering the onset, intensity, or duration of inflammation can impact the recovering hearts structure and function following myocardial infarction (MI). Substrates of MAP kinase-activated protein kinase 2 (MK2) include proteins that regulate the stability of AU-rich transcripts, including those of several pro-inflammatory cytokines. This study was to determine if MK2-deficiency impaired the inflammatory phase of post-MI wound repair. Methods and ResultsMyocardial infarctions were induced by permanent ligation of the left anterior descending coronary artery in 12-week-old male MK2+/+ and MK2-/- littermate mice. Five days post-MI, survival was 100% in MI-MK2-/- (n = 20) and 79% in MI-MK2+/+ mice (n = 29; Mandel-Cox test: P < 0.05). Area at risk and infarct size were similar. Echocardiographic imaging revealed that both systolic and diastolic LV diameters were greater in MI-MK2+/+ than MI-MK2-/- mice. MK2-deficiency did not affect the increase in wall motion score index. Infiltration of neutrophils or monocytes did not differ significantly. Cytokine and chemokine transcripts were quantified in infarcted and non-infarcted LV tissue using qPCR arrays (QIAGEN). Three days post-MI, Ifna2 was increased and Il16 was decreased in infarcted tissue from MK2-/- hearts, compared with infarcted MK2+/+ tissue, whereas in the non-infarcted MK2-/- myocardium Il27 increased and Tnfsf11, Ccl3, and Il1rn were decreased. Five days post-MI, Ctf16 and Il10 increased in infarcted MK2-/- tissue whereas in the non-infarcted MK2-/- myocardium Ccl9, Nodal, and Xcl2 increased and Il15 decreased. ConclusionsThe findings of this study suggest MK2-deficiency is an advantage during the inflammatory phase of cardiac wound repair post-MI. Clinical PerspectiveWhat is new? -The effects of MAP kinase-activated protein kinase 2 (MK2) deficiency on survival, cardiac structure and function, and the inflammatory phase of wound healing following myocardial infarction were assessed using a constitutive, pan MK2-null mouse model. -MK2-deficiency reduced mortality but did not alter area at risk or infarct size post-myocardial infarction. Inflammatory cell infiltration was also unaffected. -MK2-deficiency altered the abundance of several cytokines (increased, decreased) in infarcted and non-infarcted myocardium post-MI. What are the clinical implications? -The initial phase of wound repair post-MI involves inflammation. -The risk of damage to the myocardium and mortality may be reduced by inhibition of MK2 activity during the inflammatory phase of wound healing post-MI.

physiology↗

Explicit instruction differentially affects subcomponents of procedural learning and consolidation

Procedural memory facilitates the efficient processing of complex environmental stimuli and contributes to the acquisition of automatic behaviours and habits. Learning can occur intentionally or incidentally, yet, how the mode of learning affects procedural memory is still poorly understood. Importantly, procedural memory is a complex cognitive function composed of different subprocesses, including the acquisition and consolidation of statistical, frequency-based and sequential, order-based knowledge. Therefore, we tested how statistical and sequence knowledge develops during incidental versus intentional procedural memory formation and during consolidation. Seventy-four young adults performed either the uncued, incidental (N = 37) or the cued, intentional (N = 37) version of a probabilistic sequence learning task. Performance was retested after a 12-hour offline period, enabling us to test the effect of sleep on consolidation; therefore, half of the participants slept during the delay, while the other half had normal daily activity (PM-AM versus AM-PM design). The mode of learning (incidental versus intentional) had no effect on the acquisition of statistical knowledge, while intention to learn increased sequence learning performance. Consolidation was not affected by intention to learn: Both statistical and sequence knowledge was retained over the 12-hour delay, irrespective of the mode of learning and whether the delay included sleep or wake activity. These results suggest a time-dependent instead of sleep-dependent consolidation of both statistical and sequence knowledge. Our findings could contribute to a better understanding of how the mode of learning (intentional or incidental) affects procedural memory formation and consolidation.

neuroscience↗

Deconstructing Procedural Memory: Different Learning Trajectories and Consolidation of Sequence and Statistical Learning

Procedural learning is a fundamental cognitive function that facilitates efficient processing of and automatic responses to complex environmental stimuli. Here, we examined training-dependent and off-line changes of two sub-processes of procedural learning: namely, sequence learning and statistical learning. Whereas sequence learning requires the acquisition of order-based relationships between the elements of a sequence, statistical learning is based on the acquisition of probabilistic associations between elements. Seventy-eight healthy young adults (58 females and 20 males) completed the modified version of the Alternating Serial Reaction Time task that was designed to measure Sequence and Statistical Learning simultaneously. After training, participants were randomly assigned to one of three conditions: active wakefulness, quiet rest, or daytime sleep. We examined off-line changes in Sequence and Statistical Learning as well as further improvements after extended practice. Performance in Sequence Learning increased during training, while Statistical Learning plateaued relatively rapidly. After the off-line period, both the acquired sequence and statistical knowledge was preserved, irrespective of the vigilance state (awake, quiet rest or sleep). Sequence Learning further improved during extended practice, while Statistical Learning did not. Moreover, within the sleep group, cortical oscillations and sleep spindle parameters showed differential associations with Sequence and Statistical Learning. Our findings can contribute to a deeper understanding of the dynamic changes of multiple parallel learning and consolidation processes that occur during procedural memory formation.

neuroscience↗