Expression of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 in the somatosensory cortex of the mature rat: coexpression with high-affinity neurotrophin receptors.
Neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), are critical for the maintenance and plasticity of central nervous system (CNS) neurons. We tested the hypothesis that cortical neurons participate in redundant autocrine/paracrine systems. Three sets of studies determined the distribution of NGF-, BDNF-, and NT-3-expressing neurons, the frequency of neurons coexpressing NGF and BDNF, and the frequency of neurons expressing a neurotrophin and its associated high-affinity receptor. The distribution of NGF-, BDNF, and NT-3-immunoreactive neurons was identical. Neurotrophin-positive cells were parceled throughout the cortex, although the labeling frequency was not the same in all layers. More than 30% of the neurons in layers II/III, V, and VI were labeled, whereas only 5-10% of the neurons in layer IV was immunopositive for a neurotrophin. Some glia were also neurotrophin positive, particularly BDNF-positive glia. About 70% of the neurons in layers II/III and V coexpressed NGF and BDNF or coexpressed NGF and NT-3. Ligand-receptor colabeling was also common among cortical neurons. For example, nearly 70% of the NGF-, BDNF-, and NT-3-positive neurons in layer V colabeled with their respective high-affinity receptors, i.e., trkA, trkB, and trkC, respectively. Thus, (a) neurons express multiple neurotrophins and (b) cortical neurons (e.g., layer V neurons) contain the components required for autocrine/paracrine and/or anterograde communication (e.g., neurons in layer II/III support layer V neurons). These systems mean that the cortex is capable of regulating itself autonomously.
Pitts
A F
AF
Veterans Affairs Medical Center, and Department of Psychiatry, University of Iowa College of Medicine, Iowa City 52246-2208, USA.
Miller
M W
MW
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism*; D051381:Rats / Q000378:metabolism*; D020318:Rats, Long-Evans; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013003:Somatosensory Cortex / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor