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.