The metaplastic effects of cordycepin in hippocampal CA1 area of rats.

Metaplasticity is referred to adjustment in the requirements for induction of synaptic plasticity based on the prior history of activity. Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), has been considered to be the neural processes underlying learning and memory. Previous observations that cordycepin (an adenosine derivative) improved learning and memory seemed to be contradictory to the findings that cordycepin inhibited LTP. Therefore, we speculated that the conflicting reports of cordycepin might be related to metaplasticity. In the current study, population spike (PS) in hippocampal CA1 area of rats was recorded by using electrophysiological method in vivo. The results showed that cordycepin reduced PS amplitude in hippocampal CA1 with a concentration-dependent relationship, and high frequency stimulation (HFS) failed to induce LTP when cordycepin was intrahippocampally administrated but improved LTP magnitude when cordycepin was pre-treated. Cordycepin increased LTD induced by activating N-Methyl-D-aspartate (NMDA) receptors and subsequently facilitated LTP induced by HFS. Furthermore, we found that 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptors antagonist, could block the roles of cordycepin on LTD and LTP. Collectively, cordycepin was able to modulate metaplasticity in hippocampal CA1 area of rats through adenosine A1 receptors. These findings would be helpful to reconcile the conflicting reports in the literatures and provided new insights into the mechanisms underlying cognitive function promotions with cordycepin treatment.

Neuroprotection of cordycepin in NMDA-induced excitotoxicity by modulating adenosine A1 receptors.

Cerebral ischemia impairs physiological form of synaptic plasticity such as long-term potentiation (LTP). Clinical symptoms of cognitive dysfunction resulting from cerebral ischemia are associated with neuron loss and synaptic function impairment in hippocampus. It has been widely reported that cordycepin displays neuroprotective effect on ameliorating cognitive dysfunction induced by cerebral ischemia. Therefore, it is necessary to study whether cordycepin recovers cognitive function after brain ischemia through improving LTP induction. However, there has been very little discussion about the effects of cordycepin on LTP of cerebral ischemia so far. In the present study, we investigated the effects of cordycepin on LTP impairment and neuron loss induced by cerebral ischemia and excitotoxicity, using electrophysiological recording and Nissl staining techniques. The models were obtained by bilateral common carotid artery occlusion (BCCAO) and intrahippocampal NMDA microinjection. We also explored whether adenosine A1 receptors involve in the neuroprotection of cordycepin by using western blot. We found that cordycepin remarkably alleviated LTP impairment and protected pyramidal cell of hippocampal CA1 region against cerebral ischemia and excitotoxicity. Meanwhile, cordycepin prevented the reduction on adenosine A1 receptor level caused by ischemia but did not alter the adenosine A2A receptor level in hippocampal CA1 area. The improvement of LTP in the excitotoxic rats after cordycepin treatment could be blocked by DPCPX, a selective antagonist of adenosine A1 receptor. In summary, our findings provided new insights into the mechanisms of cordycepin neuroprotection in excitotoxic diseases, which is through regulating adenosine A1 receptor to improve LTP formation and neuronal survival.

Important candidate genes for abdominal fat content identified by linkage disequilibrium and fixation index information.

Selection for rapid growth in chickens has always been accompanied by increased fat deposition and excessive fat deposition, especially abdominal fat, cannot only decrease feed efficiency but also cause many diseases. Finding the candidate genes associated with abdominal fat deposition is essential for breeding. To identify these candidate genes, we applied linkage disequilibrium and selection signature analysis using chicken 60 k single nucleotide polymorphism (SNP) chips in two broiler lines divergently selected for abdominal fat content for 11 generations. After quality control, 46,033 SNPs were left for analysis. Using these SNPs, we found that r2 was 0.06 to 0.14 in the lean line and 0.07 to 0.13 in the fat line for all 28 chromosomes (except GGA16). Pairwise SNP distances <25 kb showed a mean r2 = 0.33 in the lean line and r2 = 0.32 in the fat line. The fixation index (FST) analysis was carried out and 46 SNPs with the top 0.1% of the FST value was detected as the loci with selection signatures. Besides FST, hapFLK was also used to detect selection signatures for abdominal fat content. A total of 11 genes, including transient receptor potential cation channel subfamily C member 4, estrogen related receptor gamma, fibroblast growth factor 13, G-protein-signaling modulator 2, RAR related orphan receptor A, phospholipase A2 group X, mitochondrial ribosomal protein L28, metadherin, calcitonin receptor like receptor, serine/threonine kinase 39, and nuclear factor I A, were detected as the important candidate genes for abdominal fat deposition based on their basic functions. The results of the present study may benefit the understanding of genetic mechanism of abdominal fat deposition in chicken.

Effects of cordycepin on spontaneous alternation behavior and adenosine receptors expression in hippocampus.

Cordycepin, an adenosine analogue, has been reported to improve cognitive function. Important roles on learning and memory of adenosine and its receptors, such as adenosine A1 and A2A receptors (A1R and A2AR), also have been shown. Therefore, we assume that the improvement of learning and memory induced by cordycepin is likely related to hippocampal adenosine content and adenosine receptor density. Here we investigated the effects of cordycepin on the short-term spatial memory by using a spontaneous alternation behavior (SAB) test in Y-maze, and then examined hippocampal adenosine content and A1R and A2AR densities. We found that orally administrated cordycepin (at dosages of 5 and 10mg/kg twice daily for three weeks) significantly increased the percent of relative alternation of mice in SAB but not altered body weight, hippocampus weight and hippocampal adenosine content. Furthermore, cordycepin decreased A2AR density in hippocampal subareas; however, cordycepin only reduced the A1R density in DG but not CA1 or CA3 region. Our results suggest that cordycepin exerts a nootropic role possibly through modulating A2AR density of hippocampus, which further support the concept that it is mostly A2AR rather than A1R to control the adaptive processes of memory performance. These findings would be helpful to provide a new window into the pharmacological properties of cordycepin for cognitive promotion.

Changes in Plasma Lipid Levels and Antioxidant Activities in Rats after Supplementation of Obtusifolin.

Obtusifolin, an anthraquinone from Cassia obtusifolia seeds, has been reported to reduce blood lipid levels in diabetic rats induced by streptozocin. However, it remains unclear whether obtusifolin possesses a lipid-lowering effect on hyperlipidemia caused by a high-fat diet. Moreover, hyperlipidemia is known to impair the endothelial function by causing oxidative stress. Therefore, in the present study, we investigated the antidyslipidemic and antioxidant effects of obtusifolin in hyperlipidemic rats induced by a high-fat diet. Rats with oral fat emulsion were used as our hyperlipidemic model. We measured the body weight of the rats, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, as well as nitric oxide, malondialdehyde, and superoxide dismutase. Our results showed that oral obtusifolin application significantly reversed the changes induced by hyperlipidemia in body weight, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Furthermore, obtusifolin treatment increased serum superoxide dismutase and nitric oxide, but reduced malondialdehyde. Collectively, our findings suggest that obtusifolin may improve hyperlipidemia by enhancing antioxidant activity. This study indicates a potential therapeutic importance of obtusifolin for ameliorating lipid dysfunction induced by a high-fat diet.