Quantitative evaluation of neurotrophin andtrk mRNA expression in visual and limbic areas along the occipito-temporo-hippocampal pathway in adult macaque monkeys
ABSTRACT The neurotrophins have been implicated in shaping and remodeling the connectivity of neural circuits. To explore the role of neurotrophins and their receptors, Trks, in cortical neural circuits of adult macaque monkeys, we determined mRNA expression levels of neurotrophins and Trk receptors in various visual and limbic areas along the occipito-temporo-hippocampal pathway by using a quantitative reverse-transcription polymerase chain reaction technique. The expression level of brain-derived neurotrophic factor (BDNF) mRNA was lowest in the primary visual cortex (V1), moderate in the temporal visual association area, and highest in the hippocampus. The expression levels of trkB mRNA isoforms, the full-length form that encodes a receptor tyrosine kinase and the truncated form that encodes a noncatalytic receptor, were also low in V1, moderate in the visual association area, and high in the entorhinal cortex. However, in contrast to their ligand BDNF, the expression levels of both trkB isoforms in the hippocampus were significantly lower than those in the entorhinal cortex. NT-3 mRNA was detectable only in the hippocampus and the entorhinal cortex, whereas both the full-length and the truncated forms of trkC mRNA were widely distributed throughout the neocortex and the limbic cortex. The expression levels of NGF and trkA mRNAs in these cortical areas were too low to determine quantitatively. The present findings suggest that, among neurotrophin/Trk signaling systems, the BDNF/TrkB-mediated signal most likely contributes to stabilization, remodeling, or both, of neural circuits in cortical areas along the occipito-temporo-hippocampal pathway in the adult macaque monkey.
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ABSTRACT: Aside from apolipoprotein E (APOE), genetic risk factors for β amyloid deposition in cognitively intact individuals remain to be identified. Brain derived neurotrophic factor (BDNF) modulates neural plasticity, which has been implicated in Alzheimer's disease. We examined in cognitively normal older adults whether the BDNF codon 66 polymorphism affects β amyloid burden and the relationship between β amyloid burden and cognitive scores, and how this relates to the effect of APOE. Amyloid load was measured by means of (18)F-flutemetamol PET in 64 community-recruited cognitively intact individuals (mean age 66, S.D. 5.1). Recruitment was stratified according to a factorial design with APOE (ε4 allele present vs absent) and BDNF (met allele at codon 66 present vs absent) as factors. Individuals in the four resulting cells were matched by the number of cases, age, and gender. Among the APOE ε4 carriers, BDNF met positive subjects had a significantly higher amyloid load than BDNF met negative subjects, while BDNF met carrier status did not have an effect in APOE ε4 noncarriers. This interaction effect was localized to precuneus, orbitofrontal cortex, gyrus rectus, and lateral prefrontal cortex. In the APOE ε4/BDNF met carriers, a significant inverse relationship existed between episodic memory scores and amyloid burden but not in any of the other groups. This hypothesis-generating experiment highlights a potential role of BDNF polymorphisms in the preclinical phase of β amyloid deposition and also suggests that BDNF codon 66 polymorphisms may influence resilience against β amyloid-related effects on cognition.01/2013; 2:512-20. DOI:10.1016/j.nicl.2013.04.001
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ABSTRACT: In the central nervous system (CNS), the expression of molecules is strictly regulated during development. Control of the spatiotemporal expression of molecules is a mechanism not only to construct the functional neuronal network but also to adjust the network in response to new information from outside of the individual, i.e., through learning and memory. Among the functional molecules in the CNS, one of the best-studied groups is the neurotrophins, which are nerve growth factor (NGF)-related gene family molecules. Neurotrophins include NGF, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4/5 in the mammal. Among neurotrophins and their receptors, BDNF and tropomyosin-related kinases B (TrkB) are enriched in the CNS. In the CNS, the BDNF-TrkB signaling pathway fulfills a wide variety of functions throughout life, such as cell survival, migration, outgrowth of axons and dendrites, synaptogenesis, synaptic transmission, and remodeling of synapses. Although the same ligand and receptor, BDNF and TrkB, act in these various developmental events, we do not yet understand what kind of mechanism provokes the functional multiplicity of the BDNF-TrkB signaling pathway. In this review, we discuss the mechanism that elicits the variety of functions performed by the BDNF-TrkB signaling pathway in the CNS as a tool of pharmacological therapy.DNA research: an international journal for rapid publication of reports on genes and genomes 12/2009; 7(4):276-85. DOI:10.2174/157015909790031210 · 2.35 Impact Factor
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ABSTRACT: One hundred years have passed since Brodmann's mapping of the mammalian neocortex. Solely on the basis of morphological observations, he envisaged the conservation and differentiation of cortical areal structures across various species. We now know that neurochemical, connectional and functional heterogeneity of the neocortex accompanies the morphological divergence observed in such cytoarchitectonic studies. Nevertheless, we are yet far from fully understanding the biological significance of this cortical heterogeneity. In this article, we review our past works on the gene expression profiling of the postnatal primate cortical areas, by quantitative real-time polymerase chain reaction (PCR), DNA array, differential display PCR and in situ hybridization analyses. These studies revealed both the overall homogeneity of gene expression across different cortical areas and the presence of a small number of genes that show markedly area-specific expression patterns. In situ hybridization showed that, among such genes, occ1 and retinol-binding protein (RBP) mRNAs are selectively expressed in the neuronal populations that seem to be involved in distinct neural processing such as sensory reception (for occ1) and associative function (for RBP). Such a molecular neuroanatomical approach has the promise to provide an important link between structure and function of the cerebral cortex.Genes Brain and Behavior 02/2006; 5 Suppl 1(S1):38-43. DOI:10.1111/j.1601-183X.2006.00193.x · 3.51 Impact Factor