Chronic Swimming Exercise Ameliorates Low-Soybean-Oil Diet-Induced Spatial Memory Impairment by Enhancing BDNF-Mediated Synaptic Potentiation in Developing Spontaneously Hypertensive Rats.

Exercise and low-fat diets are common lifestyle modifications used for the treatment of hypertension besides drug therapy. However, unrestrained low-fat diets may result in deficiencies of low-unsaturated fatty acids and carry contingent risks of delaying neurodevelopment. While aerobic exercise shows positive neuroprotective effects, it is still unclear whether exercise could alleviate the impairment of neurodevelopment that may be induced by certain low-fat diets. In this research, developing spontaneously hypertensive rats (SHR) were treated with chronic swimming exercise and/or a low-soybean-oil diet for 6 weeks. We found that performance in the Morris water maze was reduced and long-term potentiation in the hippocampus was suppressed by the diet, while a combination treatment of exercise and diet alleviated the impairment induced by the specific low-fat diet. Moreover, the combination treatment effectively increased the expression of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartic acid receptor (NMDAR), which were both down-regulated by the low-soybean-oil diet in the hippocampus of developing SHR. These findings suggest that chronic swimming exercise can ameliorate the low-soybean-oil diet-induced learning and memory impairment in developing SHR through the up-regulation of BDNF and NMDAR expression.

Downregulation of lncRNA X Inactive Specific Transcript (XIST) Suppresses Cell Proliferation and Enhances Radiosensitivity by Upregulating mir-29c in Nasopharyngeal Carcinoma Cells.

BACKGROUND LncRNA X inactive specific transcript (XIST) was reported to function as an oncogene in nasopharyngeal carcinoma cells (NPC) by sponging miR-34a-5p. However, the role of XIST in modulating the radiosensitivity of NPC cells and its mechanism still remain undefined. MATERIAL AND METHODS The expressions of XIST and miR-29c in NPC cells were evaluated by qRT-PCR. CNE1 and CNE2 cells were transfected with si-XIST, pcDNA-XIST, miR-29c mimics, anti-miR-29c, or respective controls by Lipofectamine 2000. The effects of XIST knockdown and miR-29c overexpression on cell proliferation, survival fraction, and γ-H2AX expression were investigated by CCK-8 assay, colony formation assay, immunofluorescence, and Western blot, respectively. Luciferase reporter assay and qRT-PCR analysis were performed to confirm whether XIST interacts with miR-29c and regulates its expression. RESULTS XIST was upregulated and miR-29c was downregulated in NPC cells. The expressions of XIST and miR-29c changed reversely in response to irradiation. Knockdown of XIST and miR-29c overexpression both resulted in a dramatic suppression of cell proliferation, a marked enhancement of radiosensitivity, and an obvious increase of γ-H2AX foci formation in NPC cells. Luciferase reporter assay and qRT-PCR analysis demonstrated that XIST interacts with miR-29c and negatively regulates its expression. Moreover, miR-29c inhibition abrogated XIST knockdown-induced cell proliferation inhibition and radiosensitivity increase in NPC cells. CONCLUSIONS XIST knockdown suppressed cell proliferation and enhanced radiosensitivity of NPC cells by upregulating miR-29c, providing a novel therapeutic target to improve radiotherapy efficiency for patients with NPC.

Effects of repetitive transcranial magnetic stimulation on synaptic plasticity and apoptosis in vascular dementia rats.

This study aims to determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) protects pyramidal cells from apoptosis and promotes hippocampal synaptic plasticity in a vascular dementia (VaD) rat model. Following establishment of a VaD rat model using two-vessel occlusion (2VO), learning and memory were evaluated via the Morris Water Maze (MWM), hippocampal CA1 neuron ultrastructure was examined via electron microscopy, and hippocampal synaptic plasticity was assessed by long-term potentiation (LTP). Western blot was used to detect the expression of N-methyl-d-aspartic acid receptor 1 (NMDAR1), Bcl-2, and Bax. Compared with VaD group, rats treated with low-frequency rTMS had reduced-escape latencies, increased swimming time in the target quadrant (P<0.05), and significantly less synaptic structure damage. LTP at hippocampal CA3-CA1 synapses was enhanced (P<0.05). Low-frequency rTMS significantly up-regulated NMDAR1 and Bcl-2 expression and down-regulated Bax expression. Low-frequency rTMS improves learning and memory, protects the synapse, and increases synaptic plasticity in VaD model rats. Increased Bcl-2 expression and reduced Bax expression may be a novel protective mechanism of low-frequency rTMS treatment for VaD.

Functional connectivity among spike trains in neural assemblies during rat working memory task.

Working memory refers to a brain system that provides temporary storage to manipulate information for complex cognitive tasks. As the brain is a more complex, dynamic and interwoven network of connections and interactions, the questions raised here: how to investigate the mechanism of working memory from the view of functional connectivity in brain network? How to present most characteristic features of functional connectivity in a low-dimensional network? To address these questions, we recorded the spike trains in prefrontal cortex with multi-electrodes when rats performed a working memory task in Y-maze. The functional connectivity matrix among spike trains was calculated via maximum likelihood estimation (MLE). The average connectivity value Cc, mean of the matrix, was calculated and used to describe connectivity strength quantitatively. The spike network was constructed by the functional connectivity matrix. The information transfer efficiency Eglob was calculated and used to present the features of the network. In order to establish a low-dimensional spike network, the active neurons with higher firing rates than average rate were selected based on sparse coding. The results show that the connectivity Cc and the network transfer efficiency Eglob vaired with time during the task. The maximum values of Cc and Eglob were prior to the working memory behavior reference point. Comparing with the results in the original network, the feature network could present more characteristic features of functional connectivity.

Repetitive transcranial magnetic stimulation increases excitability of hippocampal CA1 pyramidal neurons.

Repetitive transcranial magnetic stimulation (rTMS) is able to induce alteration in cortical activity and excitability that outlast the period of stimulation, which is long-term depre-ssion (LTD) or long-term potentiation (LTP)-like. Accumulating evidence shows that Na(+), Ca(2+) and K(+) channels are important for the regulation of neuronal excitability. To investigate the possible mechanisms of rTMS on regulation of intrinsic excitability in hippocampal neurons, the male or female Sprague-Dawley rats aged 2-3 d or 7-8 d were treated with 14 or 7-d's low frequency (1 Hz) rTMS (400 stimuli/d), respectively. After that, the effects of rTMS on ion channels such as Na(+)-channel, A-type K(+)-channel and Ca(2+)-channel in rat hippocampal CA1 pyramidal neurons were performed by standard whole-cell patch-clamp technique. The results showed that the peak amplitude and maximal rise slope of evoked single action potential (AP) were significantly increased after 14-d's rTMS treatment. Meanwhile, the AP threshold was significantly more depolarized in neurons after 14-d's rTMS treatment than neurons in control group that without rTMS treatment. The spontaneous excitatory post-synaptic currents (sEPSCs) frequency and amplitude of CA1 pyramidal neurons in groups with rTMS treatment (both 7 d and 14 d) were obviously increased compared with the age-matched control group. Furthermore, we found that electrophysiological properties of Na(+)-channel were markedly changed after rTMS treatment, including negative-shifted activation and inactivation curves, as well as fasten recovery rate. After rTMS application, the IA amplitude of K(+)-channel was reduced; the activation and inactivation curves of K(+)-channel were significantly shifted to right. Time constant of recovery from inactivation was also more rapid. Moreover, rTMS induced an obvious increment in the maximal current peak amplitude of Ca(2+)-channel. At the same time, there was a significant rightward shift in the activation curve and inactivation curves of Ca(2+)-channel. These data suggest that rTMS can enhance the AP and sEPSCs of hippocampal CA1 neurons. Altered electrophysiological properties of Na(+)-channel, A-type K(+) channels and Ca(2+) channels contribute to the underling mechanisms of rTMS-induced up-regulation of neural excitability.

Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) reverses Aß(1-42)-mediated memory deficits in rats.

Accumulating evidence shows the disruption of hippocampal neurotrophins secretion leads to memory deficits in Alzheimer's disease (AD) animal models. Invasive injection of exogenous neurotrophins into hippocampus reverses spatial memory deficits, but its clinical application is limited by traumatic brain injury during the injection procedure. Notably, recent studies have demonstrated that noninvasive repetitive transcranial magnetic stimulation (rTMS) increases endogenous neurotrophins contents in the brain of normal rats. Whether low-frequency rTMS can reverse Aß(1-42)-mediated decrease in hippocampal neurotrophins contents and spatial memory impairment is still unclear. Here, we reported that severe deficit in long-term potentiation (LTP) and spatial memory were observed in an Aß(1-42)-induced toxicity rat model. Furthermore, neurotrophins (NGF and BDNF) and NMDA-receptor levels were decreased after Aß injection. However, low-frequency rTMS markedly reversed the decrease in neurotrophins contents. And the rTMS-induced increment of neurotrophins up-regulated hippocampal NMDA-receptor expression. Moreover, low-frequency rTMS rescued deficits in LTP and spatial memory of rats with Aß-injection. These results indicate that low-frequency rTMS noninvasively and effectively increases hippocampal neurotrophins and NMDA-receptor contents in Aß(1-42)-induced toxicity model rats, which helps to enhance hippocampal LTP and reverses Aß(1-42)-mediated memory deficits.