Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol-Liver-Intestine Axis Health.

Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment.

Dysfunction of the Hippocampal-Lateral Septal Circuit Impairs Risk Assessment in Epileptic Mice.

Temporal lobe epilepsy, a chronic disease of the brain characterized by degeneration of the hippocampus, has impaired risk assessment. Risk assessment is vital for survival in complex environments with potential threats. However, the underlying mechanisms remain largely unknown. The intricate balance of gene regulation and expression across different brain regions is related to the structure and function of specific neuron subtypes. In particular, excitation/inhibition imbalance caused by hyperexcitability of glutamatergic neurons and/or dysfunction of GABAergic neurons, have been implicated in epilepsy. First, we estimated the risk assessment (RA) by evaluating the behavior of mice in the center of the elevated plus maze, and found that the kainic acid-induced temporal lobe epilepsy mice were specifically impaired their RA. This experiment evaluated approach-RA, with a forthcoming approach to the open arm, and avoid-RA, with forthcoming avoidance of the open arm. Next, results from free-moving electrophysiological recordings showed that in the hippocampus, ∼7% of putative glutamatergic neurons and ∼15% of putative GABAergic neurons were preferentially responsive to either approach-risk assessment or avoid-risk assessment, respectively. In addition, ∼12% and ∼8% of dorsal lateral septum GABAergic neurons were preferentially responsive to approach-risk assessment and avoid-risk assessment, respectively. Notably, during the impaired approach-risk assessment, the favorably activated dorsal dentate gyrus and CA3 glutamatergic neurons increased (∼9%) and dorsal dentate gyrus and CA3 GABAergic neurons decreased (∼7%) in the temporal lobe epilepsy mice. Then, we used RNA sequencing and immunohistochemical staining to investigate which subtype of GABAergic neuron loss may contribute to excitation/inhibition imbalance. The results show that temporal lobe epilepsy mice exhibit significant neuronal loss and reorganization of neural networks. In particular, the dorsal dentate gyrus and CA3 somatostatin-positive neurons and dorsal lateral septum cholecystokinin-positive neurons are selectively vulnerable to damage after temporal lobe epilepsy. Optogenetic activation of the hippocampal glutamatergic neurons or chemogenetic inhibition of the hippocampal somatostatin neurons directly disrupts RA, suggesting that an excitation/inhibition imbalance in the dHPC dorsal lateral septum circuit results in the impairment of RA behavior. Taken together, this study provides insight into epilepsy and its comorbidity at different levels, including molecular, cell, neural circuit, and behavior, which are expected to decrease injury and premature mortality in patients with epilepsy.

Low-cost and easy-fabrication lightweight drivable electrode array for multiple-regions electrophysiological recording in free-moving mice.

Objective.Extracellular electrophysiology has been widely applied to neural circuit dissections. However, long-term multiregional recording in free-moving mice remains a challenge. Low-cost and easy-fabrication of elaborate drivable electrodes is required for their prevalence.Approach.A three-layer nested construct (outside diameter, OD ∼ 1.80 mm, length ∼10 mm, <0.1 g) was recruited as a drivable component, which consisted of an ethylene-vinyl acetate copolymer heat-shrinkable tube, non-closed loop ceramic bushing, and stainless ferrule with a bulge twining silver wire. The supporting and working components were equipped with drivable components to be assembled into a drivable microwire electrode array with a nested structure (drivable MEANS). Two drivable microwire electrode arrays were independently implanted for chronic recording in different brain areas at respective angles. An optic fiber was easily loaded into the drivable MEANS to achieve optogenetic modulation and electrophysiological recording simultaneously.Main results.The drivable MEANS had lightweight (∼0.37 g), small (∼15 mm × 15 mm × 4 mm), and low cost (⩽$64.62). Two drivable MEANS were simultaneously implanted in mice, and high-quality electrophysiological recordings could be applied ⩾5 months after implantation in freely behaving animals. Electrophysiological recordings and analysis of the lateral septum (LS) and lateral hypothalamus in food-seeking behavior demonstrated that our drivable MEANS can be used to dissect the function of neural circuits. An optical fiber-integrated drivable MEANS (∼0.47 g) was used to stimulate and record LS neurons, which suggested that changes in working components can achieve more functions than electrophysiological recordings, such as optical stimulation, drug release, and calcium imaging.Significance.Drivable MEANS is an easily fabricated, lightweight drivable microwire electrode array for multiple-region electrophysiological recording in free-moving mice. Our design is likely to be a valuable platform for both current and prospective users, as well as for developers of multifunctional electrodes for free-moving mice.