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Publisher Summary This chapter presents a hypothesis that the interactions between brain-derived neurotrophic factor (BDNF) and its TrkB receptors may play an important role in modulating the plasticity of the adult hippocampus. BDNF, a member of the NGF family of neurotrophins, was purified as a survival promoting factor for sensory neurons. Two novel members of this neurotrophin family, neurotrophin-3 (NT-3) and neurotrophin-4/-5 (NT-4/-5)—have been recently described. Among mammalian species, there is complete conservation of the 119-amino acid sequence of mature BDNF and approximately 50% identity with the other neurotrophins. Based on the hypothesis that combined the lesions of hippocampal afferents more closely model the combination of neuroanatomical deficits of Alzheimer's disease; such lesions were chosen in the study presented in the chapter for the analysis of BDNF mechanisms. In adult rats, lesions of the perforant path were combined with the complete transections of the fimbria–fornix, which remove the majority of septal cholinergic axons and noradrenergic axons of the locus ceruleus. The effects of such lesions were studied on the temporal and subregion-specific expression of BDNF and trkB specific transcripts using quantitative in situ and northern blotting techniques. These combined lesions resulted in precisely defined, complex changes of both BDNF and trkB mRNA levels, suggesting that BDNF mechanisms play a crucial role in the synaptic rearrangements produced by hippocampal afferent lesions.

Publisher Summary This chapter discusses the effects of brain-derived neurotrophic factor (BDNF) on injured dopaminergic neurons. The degeneration of dopaminergic neurons of the substantia nigra is characteristic for Parkinson's disease and the loss of dopaminergic function is most likely responsible for the majority of behavioral deficits of the disease. The identification of a trophic factor able to promote survival and function of dopaminergic neurons and to protect them from degeneration after injury could have significant impact on the future treatment of Parkinson's disease. BDNF, a growth factor belonging to the neurotrophin protein family, which includes nerve growth factor (NGF), stimulates developmental growth and differentiation of dopaminergic neurons in culture. The pretreatment of cultured dopaminergic neurons with BDNF diminishes the susceptibility of these cells to intermediate concentrations of the selective dopaminergic neurotoxin MPP+. In contrast to these actions in vitro, it is found that intraventricular BDNF administration is unable to protect axotomized dopaminergic neurons from degeneration in a similar way as NGF offers protection for axotomized cholinergic neurons. However, these findings do not generally exclude that adult dopaminergic neurons are responsive to BDNF.