神经生物学

Most neurotransmitters, hormones, and growth factors that cause alterations in the rate of synthesis of intracellular messengers interact with cell surface receptors that are members of a family of single polypeptide proteins. Secondary and tertiary structure predictions for s ...

Changes in cytosolic free calcium ion concentration (i) accompany many cellular transitions and stimulation of cell surface receptors. Both release of Ca2+ from internal stores and Ca2+ entry through plasma membrane ion channels can contribute to cellular Ca2+ transients. In the past, d ...

Protein kinase C is a key element in signal transduction, cell regulation, and tumor promotion, influencing cellular responses to many stimuli at a variety of levels, including receptors, transduction systems, ion channels, and membrane pumps. Although it was once thought of as a single enti ...

This chapter will describe and assess the technology by which optical indicators are used to produce images that show the distribution of a measured quantity, such as free ion concentration or electric potential, within individual cells. Common ions whose free concentrations, or activi ...

Signaling pathways that convert extracellular stimuli into intracellular responses regulate many diverse physiological and biochemical processes, and share many characteristics. An external signal binds to a cell surface receptor and stimulates a transducer to activate an ...

Cyclic nucleotides were discovered about 30 years ago, becoming the prototype intracellular messengers (Robison et al., 1971). Intracellular messenger signaling systems may be split into the following divisions:

The development of caged intracellular messenger compounds offers an elegant new approach to quantitative, time-resolved studies of intracellular signaling pathways. Several reviews of caged compounds have recently appeared (Kaplan and Somlyo, 1989; McCray and Trentham, 19 ...

In contrast to unit action potentials recorded from discrete neurons, field potentials, as the name implies, are not restricted to the spatial domain of a neuron or of the brain. As a result of the volume-conducting properties of the brain, field potentials reflect activity of a population of neuro ...

After the current section, the history (1.2.) of evoked potentials (EP—for abbreviations, see the end of this chapter) is briefly presented, followed by a discussion of how EPs can be broken down into components (1.3.). General methodology (2.) is then presented, covering recording techniques (2 ...

In the past dozen years, newly developed chronic recording techniques have made possible the direct study of peripheral nerve and spinal cord function in conscious, freely moving animals. Two complementary approaches were introduced in the mid-1970s: floating microelectrodes to r ...

In addition to desensitization and downregulation of receptors at the cell membrane, the number of receptors expressed is modulated by regulation of steady-state levels of mRNA and the rate of gene transcription (see refs. 1 and 2 for reviews). Regulation of receptor mRNA and gene transcript ...

A frequently observed adaptive response to chronic agonist occupancy of cell surface receptors is a process in which receptors become internalized or sequestered into a cell compartment to which hydrophilic ligands have only a limited access (1–3). Although receptor sequestration ...

Agonist occupation of G protein-coupled receptors (GPCRs) leads to a cellular response that wanes, or desensitizes, with prolonged agonist exposure. Different cellular mechanisms contribute to desensitization, including the altered function and/or expression of recepto ...

Convection-enhanced drug delivery is a novel technology used to deliver drugs into brain tissue and which is currently evaluated in clinical trials. Drugs are delivered continuously via intracranial catheters and enable to achieve large volume of distributions at high drug concent ...

Recently, the nasal route for systemic drug delivery has gained great interest. It provides several advantages over other routes of drug administrations. These include rapid absorption, avoidance of the intestinal and hepatic presystemic disposition, and high potential for drug t ...

Intracarotid drug delivery was extensively investigated in the past; however, the approach was largely abandoned due to inconsistent benefits. Yet, intracarotid drug delivery is anecdotally used for treating a variety of brain diseases. The rapid advances in endovascular techni ...

Direct central neural axis neuromodulation has become a viable means to treat chronic neurologic disease and injury. Although first described in 1898, technology has only recently allowed for strict modulation and adjustments of drug delivery into the centeral nervous system. Evol ...

This chapter presents a mechanistic approach to in silico prediction of blood–brain barrier penetration by drugs and drug-like molecules. Focus is brought to critical analysis of experimental data used for modeling; several factors affecting data quality are discussed. The main exp ...

In the treatment of central nervous system diseases, therapeutic particles need to breach the blood–brain barrier (BBB) to reach their intended target, and it has long been known that this is a difficult barrier to breach. The barrier is both passive with tight junctions hindering passage of even ...

A major challenge to drug delivery in the brain is caused by the blood–brain barrier (BBB), a composite of endothelial structures that exclude over 98% of small-molecule drugs and almost 100% of large-molecule neurotherapeutics from being transmitted to the brain. Current strategies for ov ...