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The article presents an abstract of the research paper "Diet, lipids and brain development." Formation of a myelin sheath is one of the fundamental and necessary events in the normal development of the central nervous system in vertebrates. Myelinogenesis is basically a postnatal process in rodents.

High‐mobility group box‐1 (HMGB‐1) acts as a pro‐inflammatory cytokine contributing to the occurrence of many central inflammatory and infectious disorders. Brain mast cells (MCs) are the first responders to peripheral inflammatory stimulation because of their rapid response to external stimuli coupled with their release of preformed and newly synthesized reactive chemicals. Little is known about the involvement of brain MCs in the pro‐inflammatory effects of HMGB‐1 on the central nervous system (CNS). Thus, we investigated the activation process of MCs by HMGB‐1 and explored whether this process is involved in the pro‐inflammatory effects of HMGB‐1 on the CNS. In this study, we used P815 cells to study the activating role of HMGB‐1 on MCs and to explore its potential mechanism in vitro. In an in vivo study, adult male Sprague‐Dawley rats received i.c.v. injection of sterile saline or cromoglycate (stabilizer of MCs) 30 min prior to i.p. injection of HMGB‐1. Increased levels of tumor necrosis factor and IL‐1β were observed in the P815 cells, as well as in the rats' brains, after HMGB‐1 treatment. Pretreatment with the receptor of advanced glycation endproducts (RAGE)‐siRNA inhibited the HMGB‐1‐induced inflammatory process in the P815 cells. Activation of the RAGE/nuclear factor‐κB (NF‐κB) pathway was observed in both the P815 cells and rats' brains. In addition, HMGB‐1 induced the accumulation of brain MCs in the hippocampal CA1 region, and the blood–brain barrier was disrupted. Pretreatment with cromoglycate, a stabilizer of MCs, mitigated these HMGB‐1‐induced pro‐inflammatory processes in rats. These findings indicate that brain MCs are involved in the pro‐inflammatory effect of HMGB‐1 on the CNS, probably via activating the RAGE/NF‐κB pathway. [ABSTRACT FROM AUTHOR]

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet ( HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein ( FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation ( LKO) on the effect of high-fat diet ( HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. [ABSTRACT FROM AUTHOR]

The mechanisms underlying developmental myelination have therapeutic potential following CNS injury and degeneration. We report that transplanted central glial (CG)-4 cells had a diminished myelinating capacity in myelin-deficient ( md) rats when cells express a mutated form of Tau (Tau [688]), which binds Fyn but not the microtubules. In the brain of the md rats, Tau [688]-transfected CG-4 cells displayed a decrease in cellular process outgrowth and myelination; in the spinal cord the extent of myelination rostral and caudal to the injection site was decreased. In contrast, control Tau [605]-transfected CG-4 cells formed long cellular processes and substantial areas of myelin both in the brain and spinal cord. In culture, Tau [688]-transfected CG-4 cells displayed a decrease in cellular process outgrowth, and Fyn localized largely in the cell body, not the processes. Thus, Tau in oligodendrocytes plays a key role in myelination, and a functional Tau-Fyn interaction might have therapeutic potential during demyelination and myelin repair following CNS injury and degeneration. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (ApoE), encoded by the apolipoprotein E gene (APOE), plays an important role in the pathogenesis of Alzheimer’s disease (AD). The APOE ε4 variant is strongly associated with AD. APOE promoter polymorphisms have also been reported to associate with higher AD risk. Mouse models of APOE expression have long been used to study the pathogenesis of AD. Elucidating the role of the APOE gene in AD requires understanding of how its regulation differs between mouse and human APOE genes, and how the differences influence AD risk. We compared the structure and function of both the human APOE gene promoter (hAPOEP) and mouse APOE gene promoter (mAPOEP) regions. Homology is less than 40% at 180 bp or more upstream of the two species’ transcription start site (TSS, +1). Functional analysis revealed both similarities and important differences between the two sequences, significantly affected by human versus rodent cell line origin. We likewise probed nuclear extracts from several cell lines of different origins (astrocytic, glial, and neuronal) and mouse brain with specific hAPOEP and mAPOEP fragments. Each fragment shared DNA–protein interactions with the other but, notably, also bound distinct factors, demonstrated by gel shift and southwestern analyses. We determined possible identities for these distinct factors. These results suggest that regulation of mouse and human APOE genes may be sufficiently unique to justify the use of both the human APOE promoter sequence in transgenic rodent models and non-rodent AD models for studying factors involved in AD pathogenesis. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the study "Lipid Signal Molecules and their Regulation During Oxidative Stress in the Developing Brain." The research paper for the study would be presented in the 30th Annual Meeting of the American Society for Neurochemistry, on March 14-17, 1999, in New Orleans, Louisiana.

The article presents an abstract of a study that analyzed the role of the Delta3 isoform of Ca2+/calmodulin-dependent protein kinase II in brain-derived neurotrophic factor (BDNF) gene expression in the central nervous system. RT-PCR showed that the mRNA containing exon IV and exon V was found to be in abundance in cerebellum and NG1O8-15 cells.