Molecular Biology of the Brain (review)

Molecular Biology of the Brain, edited by S.J. Higgins. Princeton, NJ: Princeton University Press, 1999. 196 pp. $32.50.

The brain is one of the most complicated of all evolutionary adaptations, and is probably the most intriguing. How the complexities of human thought, language, cognition, consciousness, and emotion emerge from the myriad of deterministic interactions between various molecules at the most basic level is one of the greatest and most important questions facing science. The Molecular Biology of the Brain reviews the state of current knowledge about the molecular foundations of brain function and gives the reader an excellent window into some of the recent research aimed at trying to unravel the mechanisms by which the brain works (or fails to work). Written by leading researchers in this field, the volume is divided into 14 chapters that focus on a variety of questions surrounding neuronal growth and degeneration, synaptic transmission, cellular metabolism, and the molecular bases of various brain disorders and diseases. Each chapter has its own introduction, an excellent summary of the key points discussed, and a list of references specific to that particular chapter. The writing is, for the most part, clear and concise, though it is definitely not a book for a general lay audience. This book would be appropriate for a high-level undergraduate course in molecular biology, as well as for graduate courses. It would also be appropriate for individuals with a background in molecular biology who are interested in reviewing the latest research relevant to the brain. The level of prior knowledge assumed does vary from chapter to chapter, leaving some chapters much more accessible to a broader audience than others. This is the inevitable result of having different sets of authors for different chapters. The payoff is that this reasonably small book is crammed with information. Several chapters illustrate nicely how recent molecular biological techniques (such as the use of recombinant expression systems, 'knock-out' genes, and so forth) are being used to probe the mysteries of brain structure and function.

Chapter 1, written by Guy Tear, is titled "Molecular Cues that Guide the Development of Neural Connectivity." Tear reviews the molecular cues, both diffusible and substrate-bound, that guide axonal growth. A number of such signaling molecules are known, which act either as attractants or repellants: netrins, semaphirins, neuropilins, Eph receptor tyrosine kinases, ephrins, and CAMs ("cell adhesion molecules"). Many of these behave as axonal attractants in one molecular context and repellants in another. Tear discusses how these signaling molecules appear to affect the growth of the axon by reorganizing the neuronal cytoskeleton. In this chapter, one gets an excellent sense of the extremely complicated and intricate nature of the cellular interactions involved in growth and development of the nervous system.

Chapter 2, by Mark Wheatley, reviews the current knowledge of neurotransmitter receptors, which can be divided into G-protein-coupled receptors (which affect membrane potentials via effectors) and ligand-gated ion channels. These two classes differ in molecular architecture. Interestingly, there are usually more than one receptor for a given neurotransmitter, with different receptor types typically showing different responses to various agonists and antagonists. Wheatley nicely summarizes research aimed at delimiting functional areas of the receptors.

In chapter 3, Giampietro Schiavo and Gudrun Stenbeck outline the details of neurotransmitter release, focusing on the last steps leading up to exocytosis of the neurotransmitter-containing small synaptic vesicles. The various proteins known to be involved in the cascade of interactions that control this process are discussed, including the "SNARE" proteins, synaptotagmin, Rab3A and Rab3C, and phosphoinositide. Also included is a short discussion of the probable role of the cytoskeleton in synaptic vesicle mobilization, as well as hypotheses regarding the proteins involved in synaptic vesicle endocytosis.

Chapter 4 covers the role mitochondria play in neuronal life and death. Samantha L. Budd and David G. Nicholls review the substantial evidence that disturbances in mitochondrial oxidative phosphorylation (either due to mutations in mitochondrial DNA [mtDNA] itself, or due to mitochondrial inhibitors...