[Experiment-time affects the cognitive behavior in aged Sprague-Dawley rats].

In order to investigate if the experiment-time affects cognitive performance in aged rats in different learning and memory behavioral tests, the aged Sprague-Dawley (SD) rats were divided into two groups randomly and subjected to open field test, Morris water maze test and social discrimination test. The experiment of one group was conducted in 8:00 - 11:00 AM (AM group), and the other group in 15:00 - 18:00 PM (PM group). PM group exhibited higher locomotor activity than AM group in the open field test. Compared with AM group rats, PM group rats had significantly shorter swimming distance and escape latency to find the platform in Morris water maze training session, but no significant difference in the swimming velocity was observed between the two groups. And in probe-test, PM group spent more time in target quadrant than AM group. These results revealed that PM group showed better spatial learning and memory abilities than AM group. However, there was no significant difference between the two groups in social investigation index in social discrimination test. These results show that experiment-time may affect cognitive performance in Morris water maze but not in social discrimination task in aged rats. And the results indicate that experiment-time affects cognitive performance of aged rats selectively in different learning and memory behavioral tasks.

[Inhibitory effect of anterior cingulate cortex on spontaneous activity of thalamic ventrobasal nucleus neurons.].

The purpose of this study was to investigate the influence of electrical stimulation of anterior cingulate cortex (ACC) on spontaneous activity of neurons in thalamic ventrobasal nucleus (VB). Experiments were performed on 12 male Sprague-Dawley rats weighing 250-310 g (4-5 months old). According to Paxinos and Watson's coordinate atlas of the rat, the frontal and parietal cortical areas were exposed by craniotomy, the recording electrodes were then inserted into the VB (P 2.4-4.1 mm, R 2.0-3.5 mm, H 5.2-6.8 mm) and the stimulating electrodes into the ACC (A 1.1-3.0 mm, R 0.0-1.0 mm, H 1.5-2.4 mm). Single-unit activities were recorded extracellularly in the VB by glass micropipettes (impedance 3-8 MOmega) filled with 0.5 mol/L sodium acetate solution containing saturated Fast Green. To study the effects of ACC activation on the spontaneous activities of VB cells, single electrical pulse (0.2 ms duration) was delivered to the ACC by a concentric bipolar stainless steel electrode (0.32 mm outer diameter). An effective ACC stimulation was determined for each VB neuron by gradually increasing the current intensity from 0.1 mA until either a significant change in the spontaneous activity of the VB neuron was observed, or the current intensity reached 0.4 mA. The results showed that ACC stimulation significantly suppressed the spontaneous activities in 12 out of 53 VB neurons (22.6%). (1) After the stimulation was delivered to ACC, the spontaneous activities of different VB neurons were totally suppressed for different time span. (2) There was obvious dose-effect relevance between ACC stimulation intensity and their inhibitory effect. The duration of complete inhibition was prolonged with the increases in the intensity and number of stimulation impulses in ACC. (3) The stimulation in the ACC depressed the spontaneous activities of VB neurons in different forms and this inhibition exhibited an accumulative effect. All these results indicate that the stimulation of ACC exerts an inhibitory influence on the spontaneous activities of VB neurons.

Long-Term NMDAR Antagonism Correlates Weight Loss With Less Eating.

Memantine hydrochloride is an uncompetitive N-methyl-D-aspartate (NMDA) antagonist for treatment of moderate-to-severe Alzheimer's disease. Several studies have shown that memantine can significantly correct the binge-like eating behavior in human and animal models. People with overeating behavior are more likely to be obese. Therefore, we suppose that memantine would be a good candidate for the treatment of obesity. In this study, memantine was shown to increase weight loss in obese mice induced by high fat diet. Memantine was shown to decrease food intake without inducing abdominal discomfort and anxiety, suggesting that this compound would be a good candidate drug for obesity control.

Acid-sensing ion channel 1a contributes to hippocampal LTP inducibility through multiple mechanisms.

The exact roles of acid-sensing ion channels (ASICs) in synaptic plasticity remain elusive. Here, we address the contribution of ASIC1a to five forms of synaptic plasticity in the mouse hippocampus using an in vitro multi-electrode array recording system. We found that genetic deletion or pharmacological blockade of ASIC1a greatly reduced, but did not fully abolish, the probability of long-term potentiation (LTP) induction by either single or repeated high frequency stimulation or theta burst stimulation in the CA1 region. However, these treatments did not affect hippocampal long-term depression induced by low frequency electrical stimulation or (RS)-3,5-dihydroxyphenylglycine. We also show that ASIC1a exerts its action in hippocampal LTP through multiple mechanisms that include but are not limited to augmentation of NMDA receptor function. Taken together, these results reveal new insights into the role of ASIC1a in hippocampal synaptic plasticity and the underlying mechanisms. This unbiased study also demonstrates a novel and objective way to assay synaptic plasticity mechanisms in the brain.

Environmental risk factor assessment: a multilevel analysis of childhood asthma in China.

BACKGROUND: Rapid changes in socioeconomic environment and their diverse patterns in China raise a question: how socio-environmental factors affect childhood asthma in China. We performed a multilevel analysis based on a 2005 national survey to understand the association between environmental factors and asthma, and to provide insights on developing prevention strategies. METHODS: A multi-center, cross-sectional survey was conducted in 2018 school-aged children chosen from eight Chinese cities. Children of 6-13 years old were chosen randomly from schools of 39 centers in 8 cities. The multilevel analysis was made to assess both individual-level and city-level risk factors. The effect of gross domestic product (GDP) was further investigated by analysis of the factors. RESULTS: Analysis of city-level environmental factors showed that GDP [adjusted odds ratio (OR)=1.88], particulate matter with aerodynamic diameter ≤10 µm (PM10) (adjusted OR=1.37), and average humidity (adjusted OR=1.33) were strong risk factors. Further analysis of the factors decomposed GDP into two major factors, the first represented by urban construction, energy consumption, nitrogen dioxide concentration, and the second represented by health-system coverage. This suggested that the negative effects of GDP outweighed its positive effects on asthma. CONCLUSIONS: The prevalence of childhood asthma varies significantly in the eight Chinese cities. Socioenvironmental factors such as GDP, PM10 and average humidity are strong risk factors controlling individual attributes, suggesting that balance is needed between public health and economic development in China.

A novel derivative of xanomeline improved memory function in aged mice.

OBJECTIVE: To characterize the function of a new xanomeline-derived M1 agonist, 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate (EUK1001), the acute toxicity and the effects on synaptic plasticity and cognition of EUK1001 were evaluated. METHODS: To examine the median lethal dose (LD50) of EUK1001, a wide dose range of EUK1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice. RESULTS: EUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 micromol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. CONCLUSION: We conclude that EUK1001 can improve the age-related cognitive deficits.