神经生物学

Transgenic technology provides a powerful tool to study the function of a novel gene in the whole organism. The technology of transgenic rat production is receiving increasing attention. The rat is the model of choice in cardiovascular, endocrine, behavioral, and toxicology studies. This ...

Cloning strategies based on homology provide an attractive methodology for identifying novel members of a multigene family. The techniques are straightforward, with well-established protocols, and high-quality reagents are readily available. Most steps are relatively for ...

Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the mammalian nervous system and is an important mediator of numerous physiological effects (1). NPY elicits its manifold biological effects by interacting with at least six different G-protein-coupled receptors known ...

The Y4-receptor subtype shows high species diversity compared with the Y1-, Y2-, and Y5-receptor subtypes. The rodent Y4 receptor differs considerably in sequence, pharmacology, and distribution from the human Y4 receptor. To characterize further the intriguing species differenc ...

Our interest in G-protein signaling events involved in the specialized functions of the retinal pigment epithelium led us to investigate the pattern of G-protein-coupled receptor expression in this cell type. We used reverse transcriptase-coupled polymerase chain reaction (PCR) ...

The methods used to isolate genomic clones of a particular gene have changed significantly over the years. In particular, the characterization of genes with many exons, separated by large introns, increased the need for clones with large inserts. The average length of an insert contained wit ...

The nervous system is composed of a diverse population of cells selectively expressing different genes which ultimately determine the type of neurotransmitters and neuropeptides produced and released. Neuropeptide tyrosine (NPY) is one of the most abundant and widely expressed p ...

In studies on pluripotency and differentiation, teratocarcinoma cell lines have been used as alternatives to mouse embryonic stem cell lines. Teratocarcinoma cell lines cost less to maintain and they are easier to genetically manipulate. Their disadvantage, of course, is being deri ...

Signal transduction is a key process to transmit information from the extracellular milieu, and to elicit changes in the biological activity of target cells. Several cell signaling pathways can be targeted by neurotoxicants and developmental neurotoxicants. This chapter focuses ...

Neurotoxicological testing is mainly based on experimental animal models, but several cell and tissue culture models have been developed to study the mechanisms of neurotoxicity. In general, cells of human origin are attractive alternatives to the animal models for extrapolation of ...

A major goal of our cellular toxicology research has been the identification of novel targets of organophosphorous compounds (OPs), to which end we have studied the effects of sub-lethal concentrations of OPs on morphological and molecular end points in differentiating mammalian cell ...

Cataract formation during preclinical drug safety assessment studies can be a devastating safety finding during drug development based on the stage at which these findings usually occur. The lens explant culture models offer an extremely versatile and simple in vitro model to screen co ...

Most neurodegenerative diseases culminate in cell death, although it is not uncommon for signs of dysfunction to precede cell death in humans and animal models. There is considerable evidence that neuronal and glial cell death during development occurs through apoptosis but whether ap ...

Inflammation contributes to a wide variety of brain pathologies. In this chapter methods are described for using microglia and astrocytes in culture to investigate inflammatory processes and inflammatory neurodegeneration, including the use of neuronal/glial co-cultures a ...

Oxidative stress is implicated as one of the major underlying mechanisms in a variety of human diseases. Reactive radicals, derived primarily from molecular oxygen, readily attack a variety of critical biological molecules, including DNA, cellular proteins, and lipids. Since lipid p ...

Carbonyl group formation on protein side chains is a common biochemical marker of oxidative stress and is frequently observed in a variety of acute and chronic neurological diseases including stroke, Alzheimer’s disease, and Parkinson’s disease. Given that proteins are often the imme ...

The selective loss of melanin-containing dopaminergic neurons in the substantia nigra pars compacta and locus coeruleus has motivated a large number of preclinical studies aimed at understanding the molecular mechanisms involved in the neurodegeneration of dopaminergic ne ...

The use of various in vitro systems is expanding dramatically not only in basic research, but also to meet regulatory requirements for chemicals and products of various kinds. Further significant developments are certain to result from the use of in vitro systems for high-throughput scree ...

The use of 13C and 15N labeled precursors in combination with adequate analytical tools makes it possible to study metabolic pathways in cultured neural cells. The most commonly used precursors are 13C labeled glucose, lactate, glutamate and acetate. For a dynamic evaluation of intermedi ...

Glutamine (Gln) plays an important role in satisfying brain metabolic demands and as a precursor for the synthesis of glutamate and γ-aminobutyric acid (GABA). In vitro cultured cell studies have shown that carrier-mediated Gln transport between astrocytes and neurons represents a key ...