Cordycepin improved the cognitive function through regulating adenosine A2A receptors in MPTP induced Parkinson's disease mice model.

BACKGROUND: Parkinson's disease (PD), the most common neurodegenerative disorder, primarily affects dopaminergic neurons in the substantia nigra (SN). In addition to severe motor dysfunction, PD patients appear apparent cognitive impairments in the late stage. Cognitive dysfunction is accompanied by synaptic transmission damage in the hippocampus. Cordycepin has been reported to alleviate cognitive impairments in neurodegenerative diseases. PURPOSE: The study aimed to estimate the protection roles of cordycepin on cognitive dysfunction in PD model and explore the potential mechanisms. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the PD model in vivo and in vitro experiments. In the in vivo experiments, the C57BL / 6 mice were intraperitoneally injected with MPTP and intragastric administration with cordycepin. Open field test (OFT) was used to estimate the exercise ability. Spontaneous alternation behavioral (SAB) and morris water maze (MWM) tests were used to evaluate the learning and memory abilities. The hippocampal slices from C57BL / 6 and Kunming mice in the in vitro experiments were used to record field excitatory postsynaptic potential (fEPSP) by electrophysiological methods. Western blotting was used to examine the level of tyrosine hydroxylase (TH) in the in vivo experiments and the levels of adenosine A1 and A2A receptors (A1R and A2AR) in the in vitro experiments, respectively. The drugs of MPTP, cordycepin, DPCPX and SCH58261 were perfused through dissolving in artificial cerebrospinal fluid. RESULTS: Cordycepin could significantly reduce the impairments on motor, exploration, spatial learning and memory induce by MPTP. MPTP reduced the amplitude of LTP in hippocampal CA1 area but cordycepin could improve LTP amplitudes. Cordycepin at dosage of 20 mg/kg also increased the TH level in SN. In the in vitro experiments, MPTP inhibited synaptic transmission in hippocampal Schaffer-CA1 pathway with a dose-dependent relationship, while cordycepin could reverse the inhibition of synaptic transmission. Furthermore, the roles of cordycepin on synaptic transmission could been attenuated in the presence of the antagonists of A1R and A2AR, DPCPX and SCH58261, respectively. Interestingly, the level of A2AR rather than A1R in hippocampus was significantly decreased in the cordycepin group as compared to the control. CONCLUSION: The present study has showed that cordycepin could improve cognitive function in the PD model induced by MPTP through regulating the adenosine A2A receptors. These findings were helpful to provide a new strategy for the dementia caused by Parkinson's disease.

Ischemia in intracerebral hemorrhage: A comparative study of small-vessel and large-vessel diseases.

OBJECTIVE: This study aimed to compare effects of cerebral small-vessel disease (cSVD) burden and cerebral artery stenosis (CAS) on acute ischemia in intracerebral hemorrhage (ICH) and their interaction with mean arterial pressure (MAP) change. METHODS: We recruited consecutive patients with acute primary ICH. Brain magnetic resonance imaging and angiography were performed to quantify diffusion-weighted imaging (DWI) lesions, CAS, and cSVD markers, which were calculated for the total cSVD score. Multivariable regression models were adopted to explore their associations by DWI lesions size (<15 vs. ≥15 mm) and median MAP change stratification. RESULTS: Of 305 included patients (mean age 59.5 years, 67.9% males), 77 (25.2%) had DWI lesions (small, 79.2%; large, 20.8%) and 67 (22.0%) had moderate and severe CAS. In multivariable analysis, small DWI lesions were independently associated with higher total cSVD score (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.36-2.41). and large DWI lesions were associated with more severe CAS (OR 2.51, 95% CI 1.17-5.38). This association was modified by MAP change (interaction p = 0.016), with stratified analysis showing an increased risk of large DWI lesions in severe CAS with greater MAP change (≥44 mmHg) (OR 3.48, 95% CI 1.13-10.74) but not with mild MAP change (<44 mmHg) (OR 1.21, 95% CI 0.20-7.34). INTERPRETATION: Total cSVD burden is associated with small DWI lesions, whereas the degree of CAS is associated with large DWI lesions, specifically with greater MAP change, suggesting that large-artery atherosclerosis may be involved in ischemic brain injury, which is different from small-vessel pathogenesis in ICH.

Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia.

Cordycepin exerted significant neuroprotective effects and protected against cerebral ischemic damage. Learning and memory impairments after cerebral ischemia are common. Cordycepin has been proved to improve memory impairments induced by cerebral ischemia, but its underlying mechanism has not been revealed yet. The plasticity of synaptic structure and function is considered to be one of the neural mechanisms of learning and memory. Therefore, we investigated how cordycepin benefits dendritic morphology and synaptic transmission after cerebral ischemia and traced the related molecular mechanisms. The effects of cordycepin on the protection against ischemia were studied by using global cerebral ischemia (GCI) and oxygen-glucose deprivation (OGD) models. Behavioral long-term potentiation (LTP) and synaptic transmission were observed with electrophysiological recordings. The dendritic morphology and histological assessment were assessed by Golgi staining and hematoxylin-eosin (HE) staining, respectively. Adenosine A1 receptors (A1R) and adenosine A2A receptors (A2AR) were evaluated with western blotting. The results showed that cordycepin reduced the GCI-induced dendritic morphology scathing and behavioral LTP impairment in the hippocampal CA1 area, improved the learning and memory abilities, and up-regulated the level of A1R but not A2AR. In the in vitro experiments, cordycepin pre-perfusion could alleviate the hippocampal slices injury and synaptic transmission cripple induced by OGD, accompanied by increased adenosine content. In addition, the protective effect of cordycepin on OGD-induced synaptic transmission damage was eliminated by using an A1R antagonist instead of A2AR. These findings revealed that cordycepin alleviated synaptic dysfunction and dendritic injury in ischemic models by modulating A1R, which provides new insights into the pharmacological mechanisms of cordycepin for ameliorating cognitive impairment induced by cerebral ischemia.

Genipin attenuates dextran sulfate sodium-induced colitis via suppressing inflammatory and oxidative responses.

Genipin is one of the major component in Gardenis fruit, which has long been used in the treatment of many chronic diseases, such as colitis. In the present study, we investigated the protective effects and mechanism of genipin on dextran sodium sulfate (DSS)-induced colitis in mice. Colitis was induced by giving 2.5% (wt/vol) DSS for 7 days. As the results show, DSS-induced body weight loss and colonic histological changes were inhibited by the treatment of genipin. DSS-induced MPO activity, MDA level, TNF-α, and IL-1ß production in colonic tissues were also suppressed by genipin. To investigate the mechanism of genipin on DSS-induced colitis, the NF-κB and Nrf2 signaling pathways were detected. The results showed genipin significantly attenuated DSS-induced NF-κB activation and increased the expression of Nrf2 and HO-1 in a dose-dependent manner. The results of the present study indicated that genipin protected mice against colitis through inhibiting inflammatory and oxidative effects.

Cordycepin improves behavioral-LTP and dendritic structure in hippocampal CA1 area of rats.

Cordycepin, an adenosine analog, has been reported to improve cognitive function, but which seems to be inconsistent with the reports showing that cordycepin inhibited long-term potentiation (LTP). Behavioral-LTP is usually used to study long-term synaptic plasticity induced by learning tasks in freely moving animals. In order to investigate simultaneously the effects of cordycepin on LTP and behavior in rats, we applied the model of behavioral-LTP induced by Y-maze learning task through recording population spikes in hippocampal CA1 region. Golgi staining and Sholl analysis were employed to assess the morphological structure of dendrites in pyramidal cells of hippocampal CA1 area, and western blotting was used to examine the level of adenosine A1 receptors and A2A receptors (A2AR). We found that cordycepin significantly improved behavioral-LTP magnitude, accompanied by increases in the total length of dendrites, the number of intersections and spine density but did not affect Y-maze learning task. Furthermore, cordycepin obviously reduced A2AR level without altering adenosine A1 receptors level; and the agonist of A2AR (CGS 21680) rather than antagonist (SCH 58261) could reverse the potentiation of behavioral-LTP induced by cordycepin. These results suggested that cordycepin improved behavioral-LTP and morphological structure of dendrite in hippocampal CA1 but did not contribute to the improvement of learning and memory. And cordycepin improved behavioral-LTP may be through reducing the level of A2AR in hippocampus. Collectively, the effects of cordycepin on cognitive function and LTP were complex and involved multiple mechanisms.

Constructing an Associative Memory System Using Spiking Neural Network.

Development of computer science has led to the blooming of artificial intelligence (AI), and neural networks are the core of AI research. Although mainstream neural networks have done well in the fields of image processing and speech recognition, they do not perform well in models aimed at understanding contextual information. In our opinion, the reason for this is that the essence of building a neural network through parameter training is to fit the data to the statistical law through parameter training. Since the neural network built using this approach does not possess memory ability, it cannot reflect the relationship between data with respect to the causality. Biological memory is fundamentally different from the current mainstream digital memory in terms of the storage method. The information stored in digital memory is converted to binary code and written in separate storage units. This physical isolation destroys the correlation of information. Therefore, the information stored in digital memory does not have the recall or association functions of biological memory which can present causality. In this paper, we present the results of our preliminary effort at constructing an associative memory system based on a spiking neural network. We broke the neural network building process into two phases: the Structure Formation Phase and the Parameter Training Phase. The Structure Formation Phase applies a learning method based on Hebb's rule to provoke neurons in the memory layer growing new synapses to connect to neighbor neurons as a response to the specific input spiking sequences fed to the neural network. The aim of this phase is to train the neural network to memorize the specific input spiking sequences. During the Parameter Training Phase, STDP and reinforcement learning are employed to optimize the weight of synapses and thus to find a way to let the neural network recall the memorized specific input spiking sequences. The results show that our memory neural network could memorize different targets and could recall the images it had memorized.

Terahertz image reconstruction based on compressed sensing and inverse Fresnel diffraction.

The introduction of compressed sensing (CS) effectively pushes the development of single-pixel THz imaging due to reducing the experimental time and avoiding raster scanning. In this work, a CS method based on photoinduced dynamic masks is employed to recover a THz diffraction field in the time domain, and an inverse Fresnel diffraction (IFD) integral is adopted to remove the influence of the diffraction and reconstruct the sharp THz spectral image in a single-pixel THz imaging system. The compatibility of the CS and IFD algorithms are validated on the simulation and experiment. Besides, the reconstruction effects are also systematically analyzed by reducing the measurement number and varying the diffraction distance, respectively. This work supplies a novel thinking for improving the practicability of single-pixel THz imaging.

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.

Implementing artificial neural networks through bionic construction.

It is evident through biology research that, biological neural network could be implemented through two means: by congenital heredity, or by posteriority learning. However, traditionally, artificial neural network, especially the Deep learning Neural Networks (DNNs) are implemented only through exhaustive training and learning. Fixed structure is built, and then parameters are trained through huge amount of data. In this way, there are a lot of redundancies in the implemented artificial neural network. This redundancy not only requires more effort to train the network, but also costs more computing resources when used. In this paper, we proposed a bionic way to implement artificial neural network through construction rather than training and learning. The hierarchy of the neural network is designed according to analysis of the required functionality, and then module design is carried out to form each hierarchy. We choose the Drosophila's visual neural network as a test case to verify our method's validation. The results show that the bionic artificial neural network built through our method could work as a bionic compound eye, which can achieve the detection of the object and their movement, and the results are better on some properties, compared with the Drosophila's biological compound eyes.

Polarization determination based on the longitudinal field of a converging terahertz wave.

Based on coherently measuring the longitudinal field of a converging terahertz (THz) wave, a polarization determination method to the THz radiation is proposed. By utilizing the method, the arbitrary uniform polarization state of a THz field can be effectively identified in a single measurement. By using the vector diffraction integral, the principle of the method is theoretically discussed in detail. The feasibility of the method is validated experimentally by measuring a THz wire grating polarizer and a THz quarter-wave plate. The method offers a powerful technical support for developing the THz polarization spectroscopy.

Confirmation of the abnormal lipid metabolism as a risk factor for the disease of leukoaraiosis.

Our purpose is to screen out medical history indicators and test indicators linked to lipid metabolism which is closely correlated to leukoaraiosis (LA), and to build assistant diagnosis model based on support vector machine (SVM), which provided theoretical evidence for genesis and development of LA. One thousand LA patients who underwent magnetic resonance imaging (MRI) examination in Imaging Department was retrospectively analyzed and divided into LA group and non-LA group in accordance with examination results. Detailed clinical statistics of the two groups were collected, including test indicators related to lipid metabolism, such as total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), medical history indicators, age, sex, diabetes, hypertension, hyperlipidemia, history of intracranial infection, history of cerebral hemorrhage, cerebral infarction, lacunar infarction and relevant biochemical indexes. The study shows that patients' incidence of LA was 31.10%; in accordance with Logistic analysis, the incidence of LA is significantly correlated to factors like age, hypertension, history of cerebral hemorrhage, cerebral infarction, lacunar infarction and triglyceride elevation; two SVMs, one including all variables and the other containing all screened variables were successfully established, and the former's accuracy, specificity and sensitivity respectively were 85.0%, 85.0% and 85.0% while the latter's 90.0%, 100.0% and 80.0%. Test indicators and medical history indicators of lipid metabolism correlated to LA were screened out successfully. Meanwhile, an effective SVM model also was built successfully, which is able to predict LA relatively accurately and can be used as assistant diagnostic tool for clinicians.