Changes in the level of fatty acids in the brain of rats during memory acquisition.

Memory acquisition is accompanied by many cellular and molecular processes, and it is not always clear what role they play. Fatty acids (FAs) are known to be important for cognitive functions, but the details of their involvement in memory processes remain unknown. We investigated FAs in the prefrontal cortex and hippocampus of rats trained to perform a task with food reinforcement. The learning consisted of two training sessions, each of which included 10 trials. The results showed that such training altered individual FAs in the brains. The most significant changes were in the prefrontal cortex, where an increase in the level of many FAs occurred, especially after the second training session: palmitic (16:0), stearic (18:0), docosahexaenoic (22:6, n-3), arachidonic (22:4, n-6), docosapentaenoic (22:5, n-6) acids. Changes in the fatty acid level after training in rats were detected only in the left hippocampus, where the levels of palmitic, docosapentaenoic, and docosahexaenoic acids changed. The changes in the right hippocampus were not significant. In both the prefrontal cortex and the left hippocampus, 72 h after training, all FAs returned to control levels. We believe that the main role of a reversible increase in FA levels during memory acquisition is to support and protect cellular processes involved in memory acquisition. Consolidation of memory traces, which occurs mainly in the neocortex, requires protection from external influences, to which FAs makes a significant contribution. They are able to improve neuronal plasticity, enhance local blood flow, improve mitochondrial processes, and suppress pro-inflammatory signals.

Interleukin-10 and PD150606 modulate expression of AMPA receptor GluA1 and GluA2 subunits under hypoxic conditions.

The goal of this study was to evaluate the effects of anti-inflammatory cytokine, interleukin-10 (IL-10), and calpain inhibitor, PD150606, on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits in rat hippocampal slices exposed to repeated brief hypoxic episodes. We studied both individual and combinatory effects of PD150606 and IL-10 on the expression of AMPA receptor subunits under hypoxic conditions for GluA1 and GluA2 as well as their phosphorylated forms - pSer831-GluA1 and pSer880-GluA2. Additionally, we studied whether brief hypoxic episodes and IL-10 may affect mRNA expression of transcriptional factors such as hypoxia-inducible factor-1α and nuclear factor κB (NF-κB). Western blotting analysis of hippocampal slice homogenates revealed that IL-10 and PD150606, both individually and in combination, ameliorate hypoxia-induced decrease in the expression of GluA1 and pSer831-GluA1, with different level of efficiency measured at 10, 50, and 90 min after hypoxia induction. Interestingly, brief hypoxic episodes did not induce any changes in the expression of GluA2 and pSer880-GluA2 subunits, whereas PD150606 showed biphasic effect, decreasing the expression of GluA2 and pSer880-GluA2 at 10 min and potentiating it at 90 min after hypoxia induction. IL-10 alone did not show any effect but was able to reverse PD150606 action on the expression of pSer880-GluA2 at 10 min and further potentiated it for GluA2 at 90 min after hypoxia. Finally, PCR analysis revealed that modulation of GluA1 and GluA2 expressions by hypoxia, and IL-10 was not associated with changes in the expression of hypoxia-inducible factor-1α and nuclear factor-κB (NF-κB) transcriptional factors.

Interleukin-10 prevents the hypoxia-induced decreases in expressions of AMPA receptor subunit GluA1 and alpha subunit of Ca(2+)/calmodulin-dependent protein kinase II in hippocampal neurons.

The goal of this study is to evaluate the effects of anti-inflammatory cytokine interleukin-10 (IL-10) on the repeated brief hypoxia-induced changes in expressions of AMPA receptor subunit GluA1 and α- and ß-subunit of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). The hypoxia-induced changes in the rat hippocampal slice CA1 neuronal activities were investigated by the method of field potentials recording. Subunit-specific antibodies staining of Western blots of hippocampal slice homogenates to characterize the receptor subunit GluA1 and α- and ß-subunit of CaMKII were used. IL-10 (1ng/ml) abolished the development of posthypoxic hyperexcitability in the CA1 pyramidal neurons induced by repeated brief hypoxia. This neuroprotective effect of IL-10 was rapidly developed within 10min after hypoxic episodes and accompanied by reversions of the hypoxia-induced decreases in expressions of AMPA receptor subunit GluA1 and α-subunit of CaMKII. These findings provide some evidence about existence of the novel mechanism underlying the rapid neuroprotective effect of anti-inflammatory cytokine IL-10 against hypoxia-induced neurological deteriorations.