Glycosaminoglycans of brain during development.

The concentration of hyaluronic acid, chondroitin sulfate, and heparan sulfate was measured in rat brain at 2-day intervals from birth to 1 month of age, and in 40-day-old and adult animals. The levels of all three glycosaminoglycans increased after birth to reach a peak at 7 days after which they declined steadily, attaining by 30 days concentrations within 10% of those present in adult brain. The greatest change was seen in hyaluronic acid, which decreased by 50% in 3 days, and declined to adult levels (28% of the peak concentration) by 18 days of age. Only heparan sulfate showed a significant change in metabolic activity during development (a fourfold increase in the relative specific activity of glucosamine), most of which occurred after 1 week of age. In 7-day-old rats almost 90% of the hyaluronic acid in brain is extractable by water alone, as compared to only 15% in adult animals, and this large amount of soluble hyaluronic acid in young rat brain is relatively inactive metabolically. On the basis of our data we propose that the higher amounts of hyaluronic acid found in very young brain may be responsible for the higher water content of brain at these ages, and that the hydrated hyaluronic acid serves as a matrix through which neuronal migration and differentiation may take place during early brain development.     

Modularity in vertebrate brain development and evolution.

Embryonic modularity and functional modularity are two principles of brain organization. Embryonic modules are histogenetic fields that are specified by position-dependent expression of patterning genes. Within each embryonic module, secondary and higher-level pattern formation takes places during development, finally giving rise to brain nuclei and cortical layers. Defined subsets of these structures become connected by fiber tracts to form the information-processing neural circuits, which represent the functional modules of the brain. We review evidence that a group of cell adhesion molecules, the cadherins, provides an adhesive code for both types of modularity, based on a preferentially homotypic binding mechanism. Embryonic modularity is transformed into functional modularity, in part by translating early-generated positional information into an array of adhesive cues, which regulate the binding of functional neural structures distributed across the embryonic modules. Brain modularity may provide a basis for adaptability in evolution.     

Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E

With the application of genetic and molecular biology techniques, there has been substantial progress in understanding how vitamins are transferred across the mammalian blood-brain barrier and choroid plexus into brain and CSF and how vitamin homeostasis in brain is achieved. In most cases (with the exception of the sodium-dependent multivitamin transporter for biotin, pantothenic acid, and lipoic acid), the vitamins are transported by separate carriers through the blood-brain barrier or choroid plexus. Then the vitamins are accumulated by brain cells by separate, specialized systems. This review focuses on six vitamins (B(1), B(3), B(6), pantothenic acid, biotin, and E) and the newer genetic information including relevant 'knockdown' or 'knockout' models in mice and humans. The overall objective is to integrate this newer information with previous physiological and biochemical observations to achieve a better understanding of vitamin transport and homeostasis in brain. This is especially important in view of the newly described non-cofactor vitamin roles in brain (e.g. of B(1), B(3), B(6), and E) and the potential roles of vitamins in the therapy of brain disorders.     

Role of endocannabinoids in brain development.

In addition to those functions that have been extensively addressed in this special issue, such as nociception, motor activity, neuroendocrine regulation, immune function and others, the endogenous cannabinoid system seems to play also a role in neural development. This view is based on a three-fold evidence. A first evidence emerges from neurotoxicological studies that showed that synthetic and plant-derived cannabinoids, when administered to pregnant rats, produced a variety of changes in the maturation of several neurotransmitters and their associated-behaviors in their pups, changes that were evident at different stages of brain development. A second evidence comes from studies that demonstrated the early appearance of elements of the endogenous cannabinoid system (receptors and ligands) during the brain development. The atypical location of these elements during fetal and early postnatal periods favours the notion that this system may play a role in specific molecular events related to neural development. Finally, a third evidence derives from studies using cultures of fetal glial or neuronal cells. Cannabinoid receptors are present in some of these cultured cells and their activation produced a set of cellular effects consistent with a role of this system in the process of neural development. All this likely supports that endocannabinoids, early synthesized in nervous cells, play a role in events related to development, by acting through the activation of second messenger-coupled cannabinoid receptors.     

Gangliosides in the human brain development and aging.

In this study, brain gangliosides in prenatal and postnatal human life were analyzed. Immunohistochemically, the presence of "c"-pathway of gangliosides (GQ1c) in embryonic brain was only recorded at 5 weeks of gestation. Biochemical results indicated a twofold increase in human cortex ganglioside concentration between 16 and 22 weeks of gestation. The increasing ganglioside concentration was based on an increasing GD1a ganglioside fraction in all regions analyzed except cerebellar cortex, which was characterized by increasing GT1b. In this developmental period, GD3 was found to be localized in the ventricular zone of the cortical wall. After birth, GD1b ganglioside in neuropil of granular cell layer corresponding to growing mossy fibers was expressed in cerebellar cortex. Between birth and 20/30 years of age, a cerebral neocortical difference of ganglioside composition was observed, characterized by lowest GD1a in visual cortex. Analyzing the composition of gangliosides in cortical regions during aging, they were observed to follow region-specific alterations. In frontal cortex, there was a greater decrease in GD1a and GM1 than in GT1b and GD1b, but in occipital (visual) cortex there was no change in individual gangliosides. In hippocampus, GD1a moderately decreased, whereas other fractions were stable. In cerebellar cortex, GD1b and GT1b fractions decreased with aging.     

Nicotine and brain development

Preclinical studies, using primarily rodent models, have shown acetylcholine to have a critical role in brain maturation via activation of nicotinic acetylcholine receptors (nAChRs), a structurally diverse family of ligand-gated ion channels. nAChRs are widely expressed in fetal central nervous system, with transient upregulation in numerous brain regions during critical developmental periods. Activation of nAChRs can have varied developmental influences that are dependent on the pharmacologic properties and localization of the receptor. These include regulation of transmitter release, gene expression, neurite outgrowth, cell survival, and synapse formation and maturation. Aberrant exposure of fetal and neonatal brain to nicotine, through maternal smoking or nicotine replacement therapy (NRT), has been shown to have detrimental effects on cholinergic modulation of brain development. These include alterations in sexual differentiation of the brain, and in cell survival and synaptogenesis. Long-term alterations in the functional status and pharmacologic properties of nAChRs may also occur, which result in modifications of specific neural circuitry such as the brainstem cardiorespiratory network and sensory thalamocortical gating. Such alterations in brain structure and function may contribute to clinically characterized deficits that result from maternal smoking, such as sudden infant death syndrome and auditory-cognitive dysfunction. Although not the only constituent of tobacco smoke, there is now abundant evidence that nicotine is a neural teratogen. Thus, alternatives to NRT should be sought as tobacco cessation treatments in pregnant women.