BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity

Dugich-Djordjevic, Millicent M.; Tocco, Georges; Willoughby, David A.; Najm, Imad; Pasinetti, Giulio Maria; Thompson, Richard F.; Baudry, Michel; Lapchak, Paul A.; Hefti, Franz

doi:10.1016/0896-6273(92)90133-x

Cited by 206 publications

(58 citation statements)

References 48 publications

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“…BDNF mRNA has been found in proximal dendrites of hippocampal neurons in vivo (Dugich-Djordjevic et al, 1992;Schmidt-Kastner et al, 1996), although these results were not confirmed in other studies (Miranda et al, 1993;Lauterborn et al, 1996;Conner et al, 1997). Furthermore, although limbic seizures cause dramatic increases in BDNF mRNA levels (see above), its dendritic localization has not been studied under these conditions.…”

Section: Introductioncontrasting

confidence: 37%

Brain-Derived Neurotrophic Factor mRNA and Protein Are Targeted to Discrete Dendritic Laminas by Events That Trigger Epileptogenesis

Tongiorgi¹,

Armellin²,

Giulianini³

et al. 2004

J. Neurosci.

131

121

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Dendritic targeting of mRNA and local protein synthesis are mechanisms that enable neurons to deliver proteins to specific postsynaptic sites. Here, we demonstrate that epileptogenic stimuli induce a dramatic accumulation of BDNF mRNA and protein in the dendrites of hippocampal neurons in vivo. BDNF mRNA and protein accumulate in dendrites in all hippocampal subfields after pilocarpine seizures and in selected subfields after other epileptogenic stimuli (kainate and kindling). BDNF accumulates selectively in discrete dendritic laminas, suggesting targeting to synapses that are active during seizures. Dendritic targeting of BDNF mRNA occurs during the time when the cellular changes that underlie epilepsy are occurring and is not seen after intense stimuli that are non-epileptogenic, including electroconvulsive seizures and high-frequency stimulation. MK801, an NMDA receptor antagonist that can prevent epileptogenesis but not acute seizures, prevents the dendritic accumulation of BDNF mRNA, indicating that dendritic targeting is mediated via NMDA receptor activation. Together, these results suggest that dendritic accumulation of BDNF mRNA and protein play a critical role in the cellular changes leading to epilepsy.

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Section: Introductioncontrasting

confidence: 37%

Brain-Derived Neurotrophic Factor mRNA and Protein Are Targeted to Discrete Dendritic Laminas by Events That Trigger Epileptogenesis

Tongiorgi¹,

Armellin²,

Giulianini³

et al. 2004

J. Neurosci.

131

121

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“…Moreover, it is possible that the TrkB receptors may be primarily activated in postnatal animals, because BDNF transcripts are very low in the embryonic brain, and although NT-4 levels are maximal at embryonic day 13.5, they decrease rapidly, reaching the lowest level around birth . BDNF expression, however, increases postnatally, particularly in the neocortex and dentate gyrus (Dugich-Djordjevic et al, 1992;Friedman et al, 1991;Huntley et al, 1992;Förster et al, 1993;Timmusk et al, 1993Timmusk et al, , 1994, two of the regions where cell death is most pronounced in the absence of TrkB receptors.…”

Section: Discussionmentioning

confidence: 99%

TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death

et al. 1997

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Newborn mice carrying targeted mutations in genes encoding neurotrophins or their signaling Trk receptors display severe neuronal deficits in the peripheral nervous system but not in the CNS. In this study, we show that trkB (Ϫ/Ϫ) mice have a significant increase in apoptotic cell death in different regions of the brain during early postnatal life. The most affected region in the brain is the dentate gyrus of the hippocampus, although elevated levels of pyknotic nuclei were also detected in cortical layers II and III and V and VI, the striatum, and the thalamus. Furthermore, axotomized hippocampal and motor neurons of trkB (Ϫ/Ϫ) mice have significantly lower survival rates than those of wild-type littermates. These results suggest that neurotrophin signaling through TrkB receptors plays a role in the survival of CNS neurons during postnatal development. Moreover, they indicate that TrkB receptor signaling protects subpopulations of CNS neurons from injury-and axotomy-induced cell death. Key words: TrkB; CNS; cell death; axotomy; hippocampus; motor neuronNeurotrophins, including nerve growth factor (NGF), brainderived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, and NT-6, have been shown to promote neuronal survival of a variety of neuronal populations (Fariñas and Reichardt, 1996). Mutant mice lacking the genes encoding each of these neurotrophins or their receptors have illustrated the exquisite requirement of neurotrophin signaling for the survival of distinct neuronal populations in the peripheral nervous system during embryonic development (Snider, 1994;Barbacid, 1995;Fariñas and Reichardt, 1996). However, very few defects have been detected in the CNS of these mutant mice.It has been suggested (Snider, 1994;Fariñas and Reichardt, 1996) that the absence of CNS defects in these animals might be attributable to the significant overlap in the pattern of TrkB and TrkC receptors in CNS neurons Merlio et al., 1992). However, this hypothesis seems unlikely, because double mutant mice lacking both of these Trk receptors do not show any obvious defects in the CNS, at least during embryonic development (Silos-Santiago et al., 1997). These observations suggest that the growth factor requirements of CNS neurons are more complex than those of the periphery. Another possibility is that CNS neurons require only neurotrophin support during postnatal development or even in adult animals. Alternatively, the role of neurotrophins in the CNS might involve aspects of neuronal function other than survival. Indeed, neurotrophin signaling has been implicated in physiological events such as synthesis of neuroactive substances (Lindsay and Harmar, 1989;Ip et al., 1993;Nawa et al., 1993Nawa et al., , 1994Jones et al., 1994;Marty et al., 1996), synaptic efficacy and rearrangement (Lohof et al., 1993;Cabelli et al., 1995;Kang and Schuman, 1995;Korte et al., 1995;Lesser and Lo, 1995;Levine et al., 1995;Lo, 1995;Thoenen, 1995;Patterson et al., 1996) and modulation of dendritic and axonal growth (Diamond et al., 1992;Schnell ...

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“…An increase in BDNF has been temporally associated with functional maturation of cortical regions and BDNF is necessary for normal cortical development. [14][15][16][17][18][19]83 The human dorsolateral prefrontal cortex functionally matures fairly late in postnatal life and individuals may not reach their adult level of performance on tasks that depend on the DLPFC until adolescence or young adulthood. 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 .…”

Section: Evaluation Of the Evidence For Model 1fepiphenomenamentioning

confidence: 99%

“…5,[8][9][10][11][12][13] In vivo, an increase in cortical BDNF mRNA occurs contemporaneously with cortical neuron dendrite growth and synapse formation, and BDNF is critical for the maturation of excitatory synapses. [14][15][16][17][18][19][20] Cortical glutamate neurons may be dysfunctional in schizophrenia. 21 In post-mortem neurochemical and brain imaging studies, glutamate and neurochemical markers of the integrity of glutamate neurons (Nacetyl aspartate or NAA) are reduced in the prefrontal cortex of patients with schizophrenia.…”

mentioning

confidence: 99%

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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BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity

Cited by 206 publications

References 48 publications

Brain-Derived Neurotrophic Factor mRNA and Protein Are Targeted to Discrete Dendritic Laminas by Events That Trigger Epileptogenesis

Brain-Derived Neurotrophic Factor mRNA and Protein Are Targeted to Discrete Dendritic Laminas by Events That Trigger Epileptogenesis

TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death

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

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