Mid-long term forecasting of reservoir inflow using the coupling of time-varying filter-based empirical mode decomposition and gated recurrent unit.

Accurate and reliable runoff forecast is beneficial to watershed planning and management and scientific operation of water resources system. However, due to the comprehensive influence of climatic conditions, geographical environment, and human activities, the runoff series is nonlinear and non-stationary, and there are still great challenges in mid-long term runoff forecasting. In order to improve the prediction accuracy, a novel model TVF-EMD-PE-PSO-GRU (TEPPG) was proposed in this study. Firstly, several intrinsic mode functions (IMFs) were obtained by decomposing the original runoff series by time-varying filter-based empirical mode decomposition (TVF-EMD). Secondly, the permutation entropy (PE) algorithm was used to calculate the complexity of each IMF, and the IMF with similar complexity was combined. Then, the gated recurrent unit (GRU) model based on particle swarm optimization (PSO) was used to predict each IMF after merging. Finally, the prediction results of each IMF were superimposed to obtain the final results. And compared with three models such as TVF-EMD-PSO-GRU, extreme-point symmetric mode decomposition coupled gated recurrent unit and particle swarm optimization (ESMD-PSO-GRU), complete ensemble empirical mode decomposition with adaptive noise coupled gated recurrent unit, and particle swarm optimization (CEEMDAN-PSO-GRU). The monthly and annual runoff forecasting of Tangnaihai hydrological station in the upper reaches of the Yellow River and Cuntan hydrological station in the upstream of the Yangtze River was taken as examples to test the performance of the model. The results show that, compared with the other three models, the TEPPG model had the highest prediction accuracy and was relatively stable in both monthly and annual runoff forecasts. Thus, the proposed method was developed to support the decision-making of water resource system.

Activation and blockade of 5-HT6 receptor in the medial septum-diagonal band recover working memory in the hemiparkinsonian rats.

Working memory impairment is a common symptom occurred in Parkinson's disease (PD). The medial septum-diagonal band (MS-DB) complex and 5-HT6 receptor are involved in modulation of cognition. However, their roles in working memory in PD are still unknown. Here, we used behavioral, neurochemical and immunohistochemical approaches to assess the role of MS-DB 5-HT6 receptor in working memory in unilateral 6-hydroxydopamie (6-OHDA)-induced PD rats. Intra-MS-DB injection of 5-HT6 receptor agonist WAY208466 (3, 6 and 12 µg/rat) enhanced working memory and increased dopamine (DA) and noradrenaline (NA) levels in the medial prefrontal cortex (mPFC) and hippocampus in sham and 6-OHDA-lesioned rats. The dose that produced significant effect on working memory in 6-OHDA-lesioned rats was lower than that in sham rats, indicating hypersensitivity of 5-HT6 receptor after lesioning. Intra-MS-DB injection of 5-HT6 receptor antagonist SB258585 (2, 4 and 8 µg/rat) alleviated working memory deficits and increased DA level in the mPFC and hippocampus and NA level in the mPFC in 6-OHDA-lesioned rats while having no effect in sham rats, suggesting that SB258585 did not change normal cognitive status. These results suggest that activation and blockade of MS-DB 5-HT6 receptor recovered working memory in 6-OHDA-lesioned rats, which is probably related to changes in monoamine levels in the mPFC and hippocampus.

Kv7.2 subunit-containing M-type potassium channels in the lateral habenula are involved in the regulation of working memory in parkinsonian rats.

Although the lateral habenula (LHb) is involved in the regulation of multiple brain functions and this region expresses abundant M-type potassium channel (M-channel) subunits Kv7.2 and Kv7.3, the role of M-channels in regulating working memory is unclear, particularly in Parkinson's disease (PD). Here we tested the effects of activation and blockade of LHb M-channels on working memory by the T-maze rewarded alternation test in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra compacta (SNc). The SNc lesion induced working memory impairment, increased the firing rate of LHb neurons, decreased dopamine (DA) level in the ventral medial prefrontal cortex (vmPFC) and reduced the expression of Kv7.2 subunit in the LHb. Intra-LHb injection of M-channel activator retigabine induced enhancement of working memory in SNc sham-lesioned and SNc-lesioned rats; conversely, the injection of M-channel blocker XE-991 impaired working memory in the two groups of rats. However, doses producing significant effects in SNc-lesioned rats were higher than those in SNc sham-lesioned rats. Further, intra-LHb injection of retigabine decreased the firing rate of LHb neurons and increased release of DA and serotonin (5-HT) in the vmPFC, while XE-991 increased the firing rate and decreased DA and 5-HT release in the two groups of rats. Compared with SNc sham-lesioned rats, the duration of M-channel activation and blockade action on the firing rate of the neurons and release of DA and 5-HT was significantly shortened in SNc-lesioned rats, which was consistent with reduced expression of Kv7.2 subunit in the LHb after lesioning the SNc. Collectively, these findings suggest involvement of LHb Kv7.2 subunit-containing M-channels in working memory impairment in SNc-lesioned rats, and that enhanced or impaired working memory after activation or blockade of M-channels in the LHb is related to the changes in the firing activity of LHb neurons and DA and 5-HT release in the vmPFC.

Alpha-synuclein induces microglial migration via PKM2-dependent glycolysis.

After spinal cord injury, microglial cells are activated and converted to an M1 phenotype. Emerging evidence supports the hypothesis that glucose reprogramming accompanies microglial activation. What contributes to the activation of microglia and glucose reprogramming, however, remains unclear. In the current study, we investigated the role and underlying mechanism of a-synuclein in regulating the aerobic glycolysis in microglia. We found that a-synuclein contributed to the reprogramming of glucose metabolism in microglia by promoting glycolysis and inhibiting mitochondrial biogenesis and oxidative phosphorylation. Further studies demonstrated that pyruvate kinase M2 (PKM2), a rate-limiting enzyme in glycolysis, mediated glucose reprogramming regulated by a-synuclein. A co-immunoprecipitation assay and Western blot assay demonstrated that a-synuclein interacted with PKM2. Further studies demonstrated that knockdown of PKM2 in a-synuclein-exposed microglia markedly reduced glycolysis and lactate production. Additionally, a-synuclein exposure promoted migration abilities in glucose-cultured microglia, whereas migration ability was suppressed in PKM2 knockdown microglia. Additionally, the PKM2 activator TEPP-46 promoted migration ability in a-synuclein-treated microglia, compared to treatment with a-synuclein alone. In conclusion, we demonstrate a PKM2-dependent glycolysis of a-synuclein in microglial.

Α-synuclein induces microglial cell migration through stimulating HIF-1α accumulation.

Microglial cell migration and infiltration plays a critical role in spinal cord injury after thoracoabdominal aortic surgery. In our previous study, α-synuclein, a presynaptic protein was shown to be released from injured neurons and cause microglial cell activation. Here, we aimed to explore the effect of α-synuclein on microglial cell migration. Primary microglial cells were isolated from Sprague-Dawley rats and then exposed different doses (0.2, 0.4, and 0.6 µM) of α-synuclein oligomers. The mRNA and protein levels of HIF-1α were then analyzed by qRT-PCR and Western blot. Cell migration was examined by a 96-well Boyden chamber. Moreover, toll-like receptor (TLR) 2-expression as well as TLR7/8-expression was inhibited by specific siRNA transfection. HIF-1α was overexpressed by Ad-HIF-1α transfection. In the results, α-synuclein was found to stimulate HIF-1α accumulation in microglial cells in a dose-dependent manner. Silencing HIF-1α expression dampened α-synuclein induced microglial cell migration. Furthermore, blockade of TLR7/8 expression but not TLR2 expression reduced HIF-1α accumulation in microglial cells. In addition, overexpressed HIF-1α, along with Src, prompted caveolin-1 expression and phosphorylation, as well as migration in microglial cells. Α-synuclein acts via TLR7/8 and enhances HIF-1α expression, which might play a regulatory role in microglial cell migration. © 2017 Wiley Periodicals, Inc.

Elevated neuronal α-synuclein promotes microglia activation after spinal cord ischemic/reperfused injury.

The present study aimed to investigate the mechanism of injured neurons caused by ischemia/reperfusion in the induction of microglia activation. Spinal neurons were prepared and exposed to ischemic/reperfused conditions. The α-synuclein protein levels in these cells were analyzed by western blot, immunofluorescence, or enzyme-linked immunosorbent assay. Ischemia/reperfusion exposure led to elevated α-synuclein protein expression and release. Furthermore, when cocultured with injured neurons or supernatants from injured neurons, nitric oxide generation, H2O2 production, and tumor necrosis factor-α expression were promoted in microglia. Nevertheless, this effect was impeded by pretreatment of the α-synuclein antibody in the supernatants from injured neurons. Moreover, toll-like receptor 2 (TLR2) rather than TLR3 or TLR4 mediated microglia activation by α-synuclein. This process involved p38 MAPK and NF-κB activation, the inhibition of which resulted in reduced NADPH oxidase 2 (Nox2) in microglia. In conclusion, ischemia/reperfusion-injured neurons could express and release increased levels of α-synuclein and cause microglia activation through TLR2 both in vitro and in vivo.

Decreased response of interneurons in the medial prefrontal cortex to 5-HT1A receptor activation in the rat 6-hydroxydopamine Parkinson model.

This study examined the response of interneurons in the medial prefrontal cortex (mPFC) to 5-HT1A receptor agonist 8-OH-DPAT and change in expression of 5-HT1A receptor on glutamate decarboxylase 67 (GAD67)-positive neurons in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc). Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT dose-dependently inhibited the firing rate of the interneurons at all doses tested in sham-operated rats. In 6-OHDA-lesioned rats, 8-OH-DPAT, at the same doses, also inhibited the firing rate of the interneurons, whereas the inhibition was significant only at a high cumulative dose. Furthermore, injection of 8-OH-DPAT into the mPFC inhibited the interneurons in sham-operated rats, while having no effect on firing rate of the interneurons in 6-OHDA-lesioned rats. In contrast to sham-operated rats, SNc lesion reduced the expression of 5-HT1A receptor on GAD67-positive neurons in the prelimbic cortex, a sub-region of the mPFC. Our results indicate that degeneration of the nigrostriatal pathway leads to decreased response of mPFC interneurons to 5-HT1A receptor activation, which attributes to the down-regulation of 5-HT1A receptor expression in these interneurons.