Localization of Neurotrophin Proteins Within the Central Nervous System by Immunohistochemistry

Neurotrophins are a family of growth factor proteins sharing a considerable degree of primary sequence and tertiary structure homology (1 –4 ). Members of this protein family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), have been identified as important signals in the developing peripheral nervous system where they serve as survival-promoting and differentiation factors for various populations of neurons (5 ,6 ). The presence of each of these factors within the central nervous system (CNS) has also been confirmed (7 –12 ), although their physiological role in the CNS has yet to be fully elucidated. Identifying where in the CNS these proteins are made, where they are stored, how they are transferred from one cell to another, what cells they are transferred to, and their final fate are some key steps toward reaching an understanding of endogenous neurotrophin function. One technique for addressing many of these issues is immunohistochemistry. The strength of the immunohistochemical approach lies with its ability to precisely define the distribution of a given protein within a tissue sample obtained under defined experimental conditions. By manipulating the conditions under which a specimen is collected, it is possible to gain a great deal of insight into the nature by which a protein interacts within its environment and to obtain clues regarding its functional role in the animal. Nevertheless, the immunohistochemical approach has distinct limitations that must be considered when interpreting results and drawing conclusions.