The Role of Lactate in the Central Nervous System and Its Relationship with Related Diseases / 中国生物化学与分子生物学报

Lactate has always been regarded as a metabolic waste in the brain‚ and the understanding of its functions have been seriously lagging behind. In recent years‚ more and more experimental evidence has shown that lactate plays an important role in a variety of physiological and pathological processes. Among nerve cells‚ astrocytes are the main source of cells for the production and release of lactate. The cells produce lactate through aerobic glycolysis‚ which is then released to the outside of the cells via transmembrane channels and enters neurons to supply energy. In the central nervous system‚ lactate plays a significant role in homeostasis regulation. Lactate regulates the functions and activities of neurons mainly through two pathways: metabolic pathways (as energy substrates) and signal pathways (as signal molecules) ‚which is extensively manifested in the regulation of physiological processes such as neuronal energy metabolism‚ excitatory‚ plasticity‚ learning and memory‚ and nervous system development‚ as well as the pathological processes including depression‚ Alzheimer’ s disease (AD) and brain injury. There is a lactate-specific receptor (GPR81) in brain tissue‚ and lactate binds to it to regulate the intracellular second messenger. In addition‚ it was also found that lactate can modulate the excitability of neurons through unknown receptors and other functions as signal molecules. Therefore‚ this article focus on the research progress of lactate as an energy substrate and signaling molecule and its involvement in related neurological diseases‚ which may provide new ideas for the prevention and treatment of related central nervous system diseases.

The Neural Mechanisms Underlying Forgetting and Its Correlations with Nervous System Diseases / 中国生物化学与分子生物学报

Forgetting is a critical component of the memory system.On the one hand, under physiological conditions, normal forgetting helps maintain the homeostasis of the brain memory system; on the other hand, abnormal forgetting is closely related to the occurrence and development of memory- related disorders under various neural pathological conditions.In another word, forgetting is for better memory.Forgetting of unpleasant or unnecessary memories is beneficial to update new information to adapt organisms to changing environment.Abnormal forgetting is usually associated with memory-related disorders.For example, patients with Alzheimer' s disease (AD) and epilepsy have symptoms of accelerated forgetting, and post-traumatic stress disorder (PTSD) and autistic patients cannot forget unpleasant memories.Currently, the essential relation and distinction between normal forgetting under physiological conditions and abnormal forgetting under pathological conditions are still unclear, and how to improve the memory impairment of patients by regulating the forgetting proeess remains to be further studied.This review mainly foeuses on the involvement of Ras-related C3 botulinum toxin substrate 1 (Racl) , eell division cyele 42 (Cde42) , neurogenesis, microglia, dopamine and a-amino-3-hydroxy-5- methyl-4-isoxazolepropionic aeid receptors (AM PA receptors) in the regulation of forgetting under physiological conditions, and abnormal forgetting in various central pathological conditions such as AD, epilepsy, PTSD and autism, which will provide insight to the neuromolecular mechanism of forgetting and new ideas for the prevention and treatment of memory-related diseases.

Cell biological properties of microglia and its role in neurons regulation / 基础医学与临床

Microglia are resident immune cells within the brain parenchyma. In physiological conditions,microglia are highly dynamic, expressing multiple immune receptors and neurotransmitter receptors, tightly monitoring the microenvironment of central nervous system (CNS). Recent researches have revealed that these immune cells ac-tively modulate the functions of neurons,which potentially affecting neuronal activity and synaptic pruning,contrib-ute to synaptic plasticity and preventing neurotoxicity. The functional changes of microglia play an important role in the development,maturation and degeneration of the brain.

17β-estradiol protects against injury of aortic relaxation and contraction in ovariectomized rats with insulin resistance induced by fructose / 生理学报

The purpose of the present study was to investigate the effect of 17beta-estradiol (17beta-E(2)) on the structure and relaxation and contraction activity of thoracic aortas in ovariectomized rats with insulin resistance induced by fructose. Ovariectomized mature female Sprague-Dawley rats were fed with high fructose diet for 8 weeks to induce insulin resistance. Physiological dose of 17beta-E(2) (30 mug/kg) was injected subcutaneously every day for 8 weeks. Systolic blood pressure (SBP) was measured by use of tail-cuff. Serum nitric oxide (NO), estradiol (E(2)), fasting blood sugar (FBS) and fasting serum insulin (FSI) were measured respectively in each group. The insulin sensitive index (ISI) was calculated. The thoracic aortas were fixed in formalin, sliced and HE dyed. The structure of thoracic aortas, lumen breadth, media thickness, media thickness/lumen breadth ratio and media cross-section area were measured. The contraction response of thoracic aorta rings induced by L-phenylephrine (PE) and the relaxation response of thoracic aorta rings induced by ACh and sodium nitroprusside (SNP) were measured. To explore the mechanism, nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) was used. The results obtained are as follows: (1) 17beta-E(2) protected against the effect of high fructose diet, which caused an increase in SBP, hyperinsulinemia and a decrease in ISI in ovariectomized rats. (2) The structure of thoracic aortas had no significant difference among the groups. (3) Compared with the ovariectomized group (OVX) or fructose fed group (F), serum nitric oxide was significantly reduced, the contraction response of thoracic aorta rings to PE was enhanced and the relaxation response to ACh was depressed significantly in ovariectomized+fructose fed group (OVX+F). The effect of high fructose was reversed by 17beta-E(2). After pretreatment with L-NAME, the effect of 17beta-E(2), which enhanced the relaxation response of thoracic aorta rings to ACh in ovariectomized+fructose+17beta-E(2) group (OVX+F+E(2)), was partly blocked. (4) The relaxation response of thoracic aorta rings to SNP had no significant difference among the groups. (5) The contraction response of thoracic aorta rings without endothelium to PE had no significant difference among the groups. These findings suggest that 17beta-E(2) may provide protection against the effect of high fructose diet, which causes hypertension, dysfunction of endothelial cells and insulin resistance. The mechanism of this effect of 17beta-E(2) could be partly associated with the increase of NO by NOS pathway, or associated with the decrease in the level of systolic blood pressure and serum insulin, and the improvement of insulin resistance.