Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders

Hippocampus serves as a pivotal role in cognitive and emotional processes,as well as in the regulation of the hypothalamus-pituitary axis.It is known to undergo mild neurodegenerative changes during normal aging and severe atrophy in Alzheimer's disease.Furthermore,dysregulation in the hippocampal function leads to epilepsy and mood disorders.In the first section,we summarized the most salient knowledge on the role of glial cell-line-derived neurotrophic factor and its receptors focused on aging,cognition and neurodegenerative and hippocampal-related neurological diseases mentioned above.In the second section,we reviewed the therapeutic approaches,particularly gene therapy,using glial cell-line-derived neurotrophic factor or its gene,as a key molecule in the development of neurological disorders.In the third section,we pointed at the potential of regenerative medicine,as an emerging and less explored strategy for the treatment of hippocampal disorders.We briefly reviewed the use of partial reprogramming to restore brain functions,non-neuronal cell reprogramming to generate neural stem cells,and neural progenitor cells as source-specific neuronal types to be implanted in animal models of specific neurodegenerative disorders.

Identification and Characterization of the Lipid Transport System in the Tarantula Grammostola rosea

Lipids due to its hydrophobic nature are transported in the hemolymph mainly by lipoproteic fractions. In the present work we studied the lipoproteic fractions present in the hemolymph of the spider Grammostola rosea. Through ultracentrifugation two lipoproteic fractions are isolated, one of high density named Gr-HDL (δ = 1.13 - 1.15 g/ml) and the other of very high density called Gr-VHDL (δ = 1.24 - 1.27 g/ml) Gr-VHDL in hemolymph is majority in relation to Gr-HDL. In this sense Gr-VHDL fraction has 98.6% of hemolymphatic proteins, and 89.3% of lipids presents in the hemolymph. Both lipoproteic fractions possess phospholipids such as majority lipids (phosphatidylcholine and phosphatidylethanolamine) and 18:1, 16:0, 18:2 and 18:0 as the major fatty acids. In order to confirm the role played by lipoproteic fractions in vitro assays with different 14C-lipid were performed. It was observed that Gr-VHDL takes up mainly free fatty acids and triacylglycerols unlike that observed for Gr-HDL in relation to phosphatidylcholine. Through electrophoresis it was observed that Gr-VHDL has three proteins: a predominant band of 68 kDa and two others of 99 and 121 kDa. Gr-HDL displayed a predominant band of 93 kDa, and other minority of 249 kDa. In conclusion, this study reports lipid characterization of the lipoproteic fractions present in the hemolymph of the tarantula, G. rosea. The role of each lipoproteic fraction in relation to lipid uptake is sustained by in vitro assays. Similarities and differences are found when it is compared to lipoproteins of only the three species of spiders studied.

Soybean Flour Improves Fatty Acid Profile and Decreases Hepatic Triglyceride Deposition in Rats Fed with Normocaloric and Hypercaloric Diet

This study investigated the effects of replacing casein with soy flour on the fatty acids profile and triglycerides metabolism in the liver of rats that were previously fed with normocaloric and hypercaloric diets based on casein. Wistar male rats were used;one group was fed with control diet (AIN-93) and another with hypercaloric diet (AIN-93 with 34.15% sucrose, 42% fat calories) for 9 weeks. Each group was then divided into two subgroups and casein was replaced with soybean in one of them, obtaining CC (control casein), CS (control soy), HC (hypercaloric casein) and HS (hypercaloric soy), which were fed for 6 weeks. We measured triglycerides in serum, and triglycerides, total lipids, fatty acids profile, the expression of apolipoprotein B (Apo B), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol-regulatory element-binding protein 1c (SREBP-1c), mitochondrial glycerol-3-phosphate acyltransferase (mGPAT), diacylglycerol acyltransferase 2 (DGAT-2), carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptors alpha (PPARα) in liver. Histological studies were also performed. When comparing HS vs. HC, a positive effect of soybean flour on hepatic triglycerides deposits was found, possibly through the reduction in DGAT-2 expression (P < 0.01) and the increase in Apo B (P < 0.001) expression. Soybean flour also decreased fat deposits in control diets when compared with casein, decreasing the DGAT-2 (P < 0.001) expression and increasing Apo B (P < 0.001), CPT-1 (P < 0.05) and PPARα (P < 0.01) expressions. Both soy diet subgroups increased unsaturated fatty acids respect to casein diets (P < 0.01). Hepatocytes showed few lipid droplets in HS, whereas a fat deposit in HC was observed. These results suggest that replacing casein with soybean flour in normocaloric and hypercaloric diets reduces triglycerides and improves fatty acids profile in rat liver.