Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan

Romanczyk, Tara B.; Weickert, Cynthia Shannon; Webster, Maree J.; Herman, Mary M.; Akil, Mayada; Kleinman, Joel E.

doi:10.1046/j.0953-816x.2001.01858.x

Cited by 81 publications

(81 citation statements)

References 76 publications

(114 reference statements)

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“…84 Coincident with this final maturation, we have detected a two-fold induction of BDNF mRNA during the young adult period (22 years) compared to the infant and adolescent period in DLPFC 85 . Additionally, we have found a significant increase in mRNA encoding the BDNF receptor, the high-affinity tryrosine kinase-containing form (full-length trk B or trkB TK þ ), in the young adult human DLPFC 86 . The increase in trkB TK þ mRNA is prominent in layers II and III, suggesting that cortico-cortical neurons may be especially responsive to the developmental increase in BDNF 86 .…”

Section: Evaluation Of the Evidence For Model 1fepiphenomenamentioning

confidence: 82%

“…Additionally, we have found a significant increase in mRNA encoding the BDNF receptor, the high-affinity tryrosine kinase-containing form (full-length trk B or trkB TK þ ), in the young adult human DLPFC 86 . The increase in trkB TK þ mRNA is prominent in layers II and III, suggesting that cortico-cortical neurons may be especially responsive to the developmental increase in BDNF 86 . These observations are in line with other evidence suggesting that the supragranular layers of the primate frontal cortex mature quite late in postnatal life.…”

Section: Evaluation Of the Evidence For Model 1fepiphenomenamentioning

confidence: 93%

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Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

et al. 2003

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Anatomical and molecular abnormalities of excitatory neurons in the dorsolateral prefrontal cortex (DLPFC) are found in schizophrenia. We hypothesized that brain-derived neurotrophic factor (BDNF), a protein capable of increasing pyramidal neuron spine density and augmenting synaptic efficacy of glutamate, may be abnormally expressed in the DLPFC of patients with schizophrenia. Using an RNase protection assay and Western blotting, we detected a significant reduction in BDNF mRNA (mean = 23%) and protein (mean = 40%) in the DLPFC of patients with schizophrenia compared to normal individuals. At the cellular level, BDNF mRNA was expressed at varying intensities in pyramidal neurons throughout layers II, III, V, and VI of DLPFC. In patients with schizophrenia; neuronal BDNF expression was decreased in layers III, V and VI. Our study demonstrates a reduction in BDNF production and availability in the DLPFC of schizophrenics, and suggests that intrinsic cortical neurons, afferent neurons, and target neurons may receive less trophic support in this disorder.

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Section: Evaluation Of the Evidence For Model 1fepiphenomenamentioning

confidence: 82%

Section: Evaluation Of the Evidence For Model 1fepiphenomenamentioning

confidence: 93%

Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

et al. 2003

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“…In addition, we examined sema3A in frozen sections from the cerebellum of four infants (two of each sex, aged 3.5-6 months, pH 6.35-6.74, postmortem interval (PMI)18.5-38 h) taken from the series described by Romanczk et al, 32 and from adult rats with simulated PMIs ranging from 0 to 72 h. This material together allowed us to address possible ontogenic, species, and PMI-associated effects on sema3A detection.…”

Section: Subjects Studiedmentioning

confidence: 99%

The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology

et al. 2003

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The neuropathological features of schizophrenia are suggestive of a developmentally induced impairment of synaptic connectivity. Semaphorin 3A (sema3A) might contribute to this process because it is a secreted chemorepellant which regulates axonal guidance. We have investigated sema3A in the cerebellum (an area in which expression persists in adulthood), and measured its abundance in 16 patients with schizophrenia and 16 controls. In adults, sema3A was predominantly localized to the inner part of the molecular layer neuropil, whereas infants and rats showed greater labelling of Purkinje cell bodies. Sema3A was increased in schizophrenia, as shown by enzyme-linked immunosorbent assay ( þ 28%; Po0.05) and immunohistochemistry ( þ 45%; Po0.01). We also measured reelin mRNA, since reelin is involved in related developmental processes and is decreased in other brain regions in schizophrenia. Reelin mRNA showed a trend reduction in the subjects with schizophrenia (À26%; P ¼ 0.07) and, notably, was negatively correlated with sema3A. Sema3A also correlated negatively with synaptophysin and complexin II mRNAs. The results show that sema3A is elevated in schizophrenia, and is associated with downregulation of genes involved in synaptic formation and maintenance. In this respect, sema3A appears to contribute to the synaptic pathology of schizophrenia, perhaps via ongoing effects of persistent sema3A elevation on synaptic plasticity. The findings are consistent with an early neurodevelopmental origin for the disorder, and the reciprocal changes in sema3A and reelin may be indicative of a pathogenic mechanism that affects the balance between trophic and inhibitory factors regulating synaptogenesis.

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“…Gross and microscopic examination by a neuropathologist revealed no evidence of CNS pathology. Tissue was assessed for pH values as previously described (Romanczyk et al 2002). Tissue with a pH less than 5.8 was not used.…”

Section: Experimental Procedures Subjectsmentioning

confidence: 99%

Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood

Glantz¹,

Gilmore²,

Hamer³

et al. 2007

Neuroscience

228

162

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Previous studies of postnatal synaptic development in human frontal cortex have shown that synaptic density rises after birth, reaches a plateau in childhood and then decreases to adult levels by late adolescence. A similar pattern has been seen in nonhuman primate cortex. These earlier studies in human cortex are limited, however, by significant age gaps in study subjects at critical inflection points of the developmental curve. Additionally, it is unclear if synaptic development occurs in different patterns in different cortical layers in prefrontal cortex (PFC). The purpose of this study was to examine synaptic density in human PFC across development by measuring two synaptic marker proteins: synaptophysin (presynaptic), and postsynaptic density-95 (PSD-95; postsynaptic). Western blotting was used to assess the relative levels of synaptophysin and PSD-95 in dorsolateral PFC of 42 subjects, distributed in age from 18 weeks gestation to 25 years. In addition, synaptophysin immunoreactivity was examined in each layer of areas 9 and 46 of PFC in 24 subjects, ranging in age from 0.1 to 25 years. Synaptophysin levels slowly increased from birth until age 5 and then increased more rapidly to peak in late childhood around age 10. Synaptophysin subsequently decreased until the adult level was reached by mid-adolescence, around age 16. PSD-95 levels increased postnatally to reach a stable plateau by early childhood with a slight reduction in late adolescence and early adulthood. The pattern of synaptophysin immunoreactivity seen with immunohistochemistry was similar to the Western experiments but the changes across age were more subtle, with little change by layer within and across age. The developmental patterns exhibited by these synaptic marker proteins expand upon previous studies of developmental synaptic changes in human frontal cortex; synaptic density increases steadily from birth to late childhood, then decreases in early adolescence to reach adult levels by late adolescence. Keywordsadolescence; development; human; synapses; pruning; synaptogenesisThe human brain has the most protracted period of development of any species, with neurodevelopment continuing well into early adulthood. Imaging studies have shown that in the human, the overall volume of the brain increases during childhood and adolescence (Giedd Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 November 9. Sowell et al. 2002;Gilmore et al. 2007). Specifically, the cortical gray matter volume, particularly the f...

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Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan

Cited by 81 publications

References 76 publications

Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology

Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood

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