Effect of ramosetron, a 5-HT3 receptor antagonist on the severity of seizures and memory impairment in electrical amygdala kindled rats

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT3 receptor on the severity of seizures and learning and memory impairment by electrical kindling of amygdala in rats. The amygdala kindling was conducted in a chronic kindling manner in male Wistar rats. In fully kindled animals, ramosetron (as a potent and selective 5-HT3 receptor antagonist) was microinjected unilaterally (ad doses of 1, 10 or 100 µg/0.5 µl) into the EC 5 min before the novel object recognition (NOR) and Y-maze tests or kindling stimulations. Applying ramosetron at the concentration of 100 μg/0.5 µl (but not at 1 and 10 µg/0.5 µl) reduced afterdischarge (AD) duration and increased stage 4 latency in the kindled rats. Moreover, the obtained data from the NOR test showed that treatment by ramosetron (10 and 100 µg/0.5 µl) increased the discrimination index in the fully kindled animals. Microinjection of ramosetron (10 and 100 µg/0.5 µl) in fully kindled animals reversed the kindling induced changes in the percentage of spontaneous alternation in Y-maze task. The findings demonstrated an anticonvulsant role for a selective 5-HT3 receptor antagonist microinjected into the EC, therefore, suggesting an excitatory role for the EC 5-HT3 receptors in the amygdala kindling model of epilepsy. This anticonvulsive effect was accompanied with a restoring effect on cognitive behavior in NOR and Y-maze tests.

Quantitative assessment of the central versus peripheral effect of intravenous clonidine using baroreflex equilibrium diagrams

Clonidine is a first-generation central antihypertensive that reduces sympathetic nerve activity (SNA). Although clonidine also exerts peripheral vasoconstriction, the extent to which this vasoconstriction offsets the centrally mediated arterial pressure (AP)-lowering effect remains unknown. In anesthetized rats (n = 8), we examined SNA and AP responses to stepwise changes in carotid sinus pressure under control conditions and after intravenous low-dose (2 μg/kg) and high-dose clonidine (5 μg/kg). In the baroreflex equilibrium diagram analysis, the operating-point AP under the control condition was 115.2 (108.5–127.7) mmHg [median (25th–75th percentile range)]. While the operating-point AP after low-dose clonidine was not significantly different with or without the peripheral effect, the operating-point AP after high-dose clonidine was higher with the peripheral effect than without [81.3 (76.2–98.2) mmHg vs. 70.7 (57.7–96.9), P < 0.05]. The vasoconstrictive effect of clonidine partly offset the centrally mediated AP-lowering effect after high-dose administration.

Adipose tissue macrophages in aging-associated adipose tissue function

Abstract“Inflammaging” refers to the chronic, low-grade inflammation that characterizes aging. Aging, like obesity, is associated with visceral adiposity and insulin resistance. Adipose tissue macrophages (ATMs) have played a major role in obesity-associated inflammation and insulin resistance. Macrophages are elevated in adipose tissue in aging. However, the changes and also possibly functions of ATMs in aging and aging-related diseases are unclear. In this review, we will summarize recent advances in research on the role of adipose tissue macrophages with aging-associated insulin resistance and discuss their potential therapeutic targets for preventing and treating aging and aging-related diseases.

Differences in olfactory habituation between orthonasal and retronasal pathways

The odorant arrives at nasal olfactory epithelium ortho- and retronasally. This experiment aimed to study the potential different olfactory habituation in orthonasal and retronasal pathways. 68 subjects were stimulated by constant airflow with an odor (50% phenethyl alcohol, PEA or 5% n-butyl acetate, BA) presented ortho- or retronasally. Participants rated the perceived odor intensity (0–10 points) per minute until the odor sensation disappeared. We also investigated the cross-habituation: when the subjects achieved full habituation, continue to rate odor intensity in a different pathway after instantly switching the odor stimulation pathway. The olfactory habituation curve was drawn. The differences of ratings between the orthonasal and retronasal olfaction at different time points and between male and female subjects were analyzed. The two odor intensity ratings decreased as the time extended, share the same “fast followed by slow” type. The ratings of orthonasal olfaction decreased faster than that of retronasal. The intensity rating of PEA of male retronasal approach was lower than that of female at the 5th min (p = 0.018). When orthonasal full habituation achieved, there was significant difference between the intensity ratings and the initial ratings of the retronasal stimulation pathway (p < 0.0001), and vice versa. We found obvious habituation as well as cross-habituation in both orthonasal and retronasal olfaction. The habituation of orthonasal olfaction was faster than that of retronasal olfaction. These different habituations were related to the gender.

Swimming training and Plantago psyllium ameliorate cognitive impairment and glucose tolerance in streptozotocin–nicotinamide-induced type 2 diabetic rats

Brain malfunction is common in diabetic patients. On the other hand, a growing body of research points to the beneficial effect of medicinal plants and exercise training on insulin sensitivity and brain function. Therefore, the aim of the present study was to investigate the effect of co-administration of swimming training and Plantago psyllium (mixed with standard pelleted food at a weight ratio of 5%) on learning and memory impairment and glucose tolerance in type 2 diabetic rats. For this purpose, 10 healthy and 40 rats with type 2 diabetes were randomly allocated to five groups: healthy sedentary control group (Con), sedentary diabetic group (D), diabetic group subjected to swimming training (D + Tr), diabetic group receiving P. psyllium (D + Ps), and diabetic group subjected to swimming training and receiving P. psyllium (D + Ps + Tr). Diabetes was induced by a single intraperitoneal injection of nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) separately with 15 min intervals. Experimental groups were treated with swimming training and P. psyllium independently and simultaneously for 12 weeks. Lipid profile and food intake were measured and also, glucose tolerance was evaluated by glucose area under the curve (AUCg) using an oral glucose tolerance test. Passive avoidance learning (PAL) and memory were evaluated by shuttle box test and cognitive memory was assessed by novel object recognition (NOR) and elevated plus-maze (EPM) tests. Diabetic rats exhibited a significant increase in food intake, lipid profile, and AUCg compared to healthy rats. Step-through latency in the PAL acquisition trial (STL-a) and retention test (STL-r) were significantly lower in diabetic rats than in the control group. In the diabetic group without treatment, time spent in the dark compartment increased compared to the control group in the shuttle box test. Discrimination index and distance traveled reduced in diabetic rats. On the other hand, swimming training and P. psyllium alleviated food intake, lipid profile, and glucose tolerance in diabetic rats. Also, the STL-a, STL-r, discrimination index, and distance travelled in the D + Ps + Tr group were significantly more than the diabetic group. Results showed that 12 weeks of swimming training and receiving P. psyllium improved memory deficit in streptozotocin–nicotinamide-induced type 2 diabetic rats possibly through hypolipidemic and hypoglycemic effects. These results suggest that the administration of swimming training and P. psyllium simultaneously might be an effective intervention for the treatment of diabetes-induced behavioral deficits.

Diurnal variations in muscle and liver glycogen differ depending on the timing of exercise

It has been suggested that glycogen functions not only in carbohydrate energy storage, but also as molecular sensors capable of activating lipolysis. This study aimed to compare the variation in liver and muscle glycogen during the day due to different timing of exercise. Nine healthy young men participated in two trials in which they performed a single bout of exercise at 70% of their individual maximal oxygen uptake for 60 min in the post-absorptive (morning) or post-prandial (afternoon) state. Liver and muscles glycogen levels were measured using carbon magnetic resonance spectroscopy (13C MRS). Diurnal variations in liver and muscle glycogen compared to baseline levels were significantly different depending on the timing of exercise. The effect of the timing of exercise on glycogen fluctuation is known to be related to a variety of metabolic signals, and the results of this study will be useful for future research on energy metabolism.

Brain is modulated by neuronal plasticity during postnatal development

Neuroplasticity is referred to the ability of the nervous system to change its structure or functions as a result of former stimuli. It is a plausible mechanism underlying a dynamic brain through adaptation processes of neural structure and activity patterns. Nevertheless, it is still unclear how the plastic neural systems achieve and maintain their equilibrium. Additionally, the alterations of balanced brain dynamics under different plasticity rules have not been explored either. Therefore, the present article primarily aims to review recent research studies regarding homosynaptic and heterosynaptic neuroplasticity characterized by the manipulation of excitatory and inhibitory synaptic inputs. Moreover, it attempts to understand different mechanisms related to the main forms of synaptic plasticity at the excitatory and inhibitory synapses during the brain development processes. Hence, this study comprised surveying those articles published since 1988 and available through PubMed, Google Scholar and science direct databases on a keyword-based search paradigm. All in all, the study results presented extensive and corroborative pieces of evidence for the main types of plasticity, including the long-term potentiation (LTP) and long-term depression (LTD) of the excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs).

Cardioprotective responses to aerobic exercise-induced physiological hypertrophy in zebrafish heart

Herein, we aimed to establish an aerobic exercise-induced physiological myocardial hypertrophy zebrafish (Danio rerio) model and to explore the underlying molecular mechanism. After 4 weeks of aerobic exercise, the AMR and Ucrit of the zebrafish increased and the hearts were enlarged, with thickened myocardium, an increased number of myofilament attachment points in the Z-line, and increased compaction of mitochondrial cristae. We also found that the mTOR signaling pathway, angiogenesis, mitochondrial fusion, and fission event, and mitochondrial autophagy were associated with the adaptive changes in the heart during training. In addition, the increased mRNA expression of genes related to fatty acid oxidation and antioxidation suggested that the switch of energy metabolism and the maintenance of mitochondrial homeostasis induced cardiac physiological changes. Therefore, the zebrafish heart physiological hypertrophy model constructed in this study can be helpful in investigating the cardioprotective mechanisms in response to aerobic exercise.

Shen Qi Li Xin formula improves chronic heart failure through balancing mitochondrial fission and fusion via upregulation of PGC-1α

Background Our previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear. Methods H&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress. Results In vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress. Conclusion Overall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical.

From digestion and absorption to innate immunity and health care: water and food intake may contribute to IL-22 in ILC3-dependent mucosal immunity in the jejunum

In this review, with our current studies we demonstrated medical evidence that water and food intake are useful for IL-22-related mucosal immunity-dependent maintenance of health care. The traditional Japanese health care practices recommend daily consumption of suitable volume of water. However, immunological mechanisms that support of the traditional practices are still unsolved. We focused on type 3 innate lymphoid cells (ILC3s), because the ILC3s are mainly housed in the lamina propria of the jejunum. IL-22 released from the ILC3 is transported through mesenteric lymph in collaboration with the albumin-mediated movement of consumed water. Thus, water intake-mediated upregulation of IL-22-dependent mucosal immunity contributes to the traditional Japanese health care practices. We also reviewed current studies that food intake-mediated increase in VIP-dependent neuronal activity in the small intestine and the food intake included with tryptophan-derived metabolites may accelerate the IL-22 in ILC3s-dependent mucosal immunity and then contribute in keeping health care.