Expression of brain-derived neurotrophic factor, neurotrophin-3 and their receptor messenger RNAs in monkey rhinal cortex

Hashimoto, Takako; Okuno, Hiroyuki; Tokuyama, Wataru; Li, Y.X.; Miyashita, Yasushi

doi:10.1016/s0306-4522(99)00447-9

Cited by 14 publications

(18 citation statements)

References 42 publications

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“…The anatomical distribution of BDNF mRNA in the adult human DLFPC observed in our study is in good agreement with previous reports in the primate neocortex that show prominent but uneven expression of BDNF mRNA in cortical pyramidal neurons of layers III, V, and VI. 47,56,57 Three nonmutually exclusive models could explain the BDNF reduction in pyramidal neurons of the DLFPC of patients with schizophrenia: (1) BDNF is reduced as an epiphenomenon of having a chronic mental illness and/or because of antipsychotic drug treatment of patients with schizophrenia, (2) BDNF expression is altered in patients with schizophrenia because of the more frequent inheritance of an altered BDNF 'gene', and (3) BDNF fails to be induced during normal brain development because of complex genetic and/or environmental signals, which interact to impair the normal development of the DLFPC in patients with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…At the cellular level, we noted that BDNF mRNA was not expressed uniformly in all cortical neurons ( Figure 5), consistent with reports in the monkey cortex. 56,57 Therefore, cell-based quantitation was undertaken as a more sensitive way to measure BDNF expression levels between the two subject groups.…”

Section: Bdnf In Situ Hybridizationmentioning

confidence: 99%

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

et al. 2003

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“…Our findings demonstrate that the sensory tuning of cortical neurons can be quite plastic on the hour time scale in certain behavioral contexts. The mechanisms of this plasticity are a current subject of research (21,39) and likely involve the modification of the strength of synaptic connections between neurons that represent the stimuli from the same pair and different pairs. These mechanisms and the roles that the hippocampus and other temporal lobe memory structures may play in effecting these changes are important targets for future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike stimulus-reward and stimulus-response associations, which can be learned in minutes, monkeys generally take many days to learn conditional associations between pairs of stimuli (18)(19)(20)(21). Thus, until now, the neuronal substrates of conditional stimulus-stimulus associations have been inferred only from patterns of neuronal selectivity recorded after learning has taken place (1,2,(4)(5)(6)(7)(8)(22)(23)(24)(25)(26)(27).…”

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confidence: 99%

Neuronal representations of stimulus associations develop in the temporal lobe during learning

Messinger

Squire

Zola

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

156

139

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Visual stimuli that are frequently seen together become associated in long-term memory, such that the sight of one stimulus readily brings to mind the thought or image of the other. It has been hypothesized that acquisition of such long-term associative memories proceeds via the strengthening of connections between neurons representing the associated stimuli, such that a neuron initially responding only to one stimulus of an associated pair eventually comes to respond to both. Consistent with this hypothesis, studies have demonstrated that individual neurons in the primate inferior temporal cortex tend to exhibit similar responses to pairs of visual stimuli that have become behaviorally associated. In the present study, we investigated the role of these areas in the formation of conditional visual associations by monitoring the responses of individual neurons during the learning of new stimulus pairs. We found that many neurons in both area TE and perirhinal cortex came to elicit more similar neuronal responses to paired stimuli as learning proceeded. Moreover, these neuronal response changes were learning-dependent and proceeded with an average time course that paralleled learning. This experiencedependent plasticity of sensory representations in the cerebral cortex may underlie the learning of associations between objects.

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“…The fragments for TrkB and TrkC mRNAs were amplified from the regions encoding the intracellular domains that are specific to the tyrosine kinase-containing isoforms. Antisense riboprobes transcribed from these fragments were shown to detect the specific signal of targeted mRNAs in the primate neocortex (Okuno et al, 1999;Hashimoto et al, 2000). To increase signal intensity for BDNF mRNA, we amplified an additional 358 bp fragment, corresponding to bases 693-1037 of the BDNF mRNA (GenBank accession number M61181), and combined the two antisense riboprobes transcribed from the two fragments.…”

Section: Methodsmentioning

confidence: 99%

Relationship of Brain-Derived Neurotrophic Factor and Its Receptor TrkB to Altered Inhibitory Prefrontal Circuitry in Schizophrenia

Hashimoto¹,

Bergen²,

Nguyen³

et al. 2005

J. Neurosci.

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366

292

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Dysfunction of inhibitory neurons in the prefrontal cortex (PFC), represented by decreased expression of GABA-related genes such as the 67 kDa isoform of glutamate decarboxylase (GAD 67 ) and parvalbumin (PV), appears to contribute to cognitive deficits in subjects with schizophrenia. We investigated the involvement of signaling mediated by brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB in producing the altered GABA-related gene expression in schizophrenia. In 15 pairs of subjects with schizophrenia and matched control subjects, both BDNF and TrkB mRNA levels, as assessed by in situ hybridization, were significantly decreased in the PFC of the subjects with schizophrenia, whereas the levels of mRNA encoding the receptor tyrosine kinase for neurotrophin-3, TrkC, were unchanged. In this cohort, within-pair changes in TrkB mRNA levels were significantly correlated with those in both GAD 67 and PV mRNA levels. Decreased BDNF, TrkB, and GAD 67 mRNA levels were replicated in a second cohort of 12 subject pairs. In the combined cohorts, the correlation between within-pair changes in TrkB and GAD 67 mRNA levels was significantly stronger than the correlation between the changes in BDNF and GAD 67 mRNA levels. Neither BDNF nor TrkB mRNA levels were changed in the PFC of monkeys after a long-term exposure to haloperidol. Genetically introduced decreases in TrkB expression, but not in BDNF expression, also resulted in decreased GAD 67 and PV mRNA levels in the PFC of adult mice; in addition, the cellular pattern of altered GAD 67 mRNA expression paralleled that present in schizophrenia. Decreased TrkB signaling appears to underlie the dysfunction of inhibitory neurons in the PFC of subjects with schizophrenia.

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Expression of brain-derived neurotrophic factor, neurotrophin-3 and their receptor messenger RNAs in monkey rhinal cortex

Cited by 14 publications

References 42 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

Neuronal representations of stimulus associations develop in the temporal lobe during learning

Relationship of Brain-Derived Neurotrophic Factor and Its Receptor TrkB to Altered Inhibitory Prefrontal Circuitry in Schizophrenia

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