Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y

Takahashi, Makoto; Hayashi, Shigenari; Kakita, Akiyoshi; Wakabayashi, Keiji; Fukuda, Masafumi; Kameyama, Shigeki; Tanaka, Ryuichi; Takahashi, Hitoshi; Nawa, Hiroyuki

doi:10.1016/s0006-8993(98)01355-9

Cited by 111 publications

(69 citation statements)

References 23 publications

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“…78 Moreover, the latter observation cannot be mimicked by neuroleptic treatment of rodents, thus indicating a significant link between the neurotrophic abnormality and schizophrenia itself. Similarly altered expression of BDNF is, however, often found in other neuropsychiatric diseases such as epilepsy 79 and depression. 80 Although it is uncertain whether psychotic symptoms of these diseases directly involve such alteration in neurotrophin signaling, the neurotrophic factor BDNF, at least, serves as a good molecular marker reflecting functional conditions of the brain.…”

Section: Neuronal Differentiation and Trophic Factors In Schizophreniamentioning

confidence: 99%

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

2000

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Medical treatment with various cytokines can provoke psychiatric symptoms. Conversely, psychiatric patients can display abnormalities in cytokine and neurotrophic factor expression. Such observations have pointed to the potential contribution of cytokines and growth factors to schizophrenic pathology and/or etiology. The cellular targets of the relevant factors and the nature of their actions remain to be explored in mental illness, however. Recent physiological studies demonstrate that cytokines and neurotrophic factors can markedly influence synaptic transmission and plasticity upon acute or chronic application. Moreover, many of the molecular alterations observed in the schizophrenic brain are consistent with abnormalities in cytokine and neurotrophic factor regulation of these molecules. In this review, we summarize these molecular pathology findings for schizophrenia and highlight the neurodevelopmental activities of cytokines and neurotrophic factors that may contribute to the etiology or pathology of this illness. Molecular Psychiatry (2000) 5, 594-603.

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Section: Neuronal Differentiation and Trophic Factors In Schizophreniamentioning

confidence: 99%

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

2000

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“…In fact, it has been reported that in experimental models and in epileptic patients both BDNF mRNA and protein levels are increased in the foci of seizures (Gall, 1993;Humpel et al, 1993;Isackson et al, 1991;Schmidt-Kastner et al, 1996;Takahashi et al, 1999;Jankowsky and Patterson, 2001). It has also been shown that striatal mRNA of TrkB is transiently elevated after seizures (Merlio et al, 1993;Salin et al, 1995) and that epileptiform activity induces a strong upregulation of cortical TrkB (Wyneken et al, 2001(Wyneken et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

TrkB/BDNF-Dependent Striatal Plasticity and Behavior in a Genetic Model of Epilepsy: Modulation by Valproic Acid

Ghiglieri

Sgobio

Patassini

et al. 2010

Neuropsychopharmacol

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In mice lacking the central domain of the presynaptic scaffold Bassoon the occurrence of repeated cortical seizures induces cell-typespecific plasticity changes resulting in a general enhancement of the feedforward inhibition within the striatal microcircuit. Early antiepileptic treatment with valproic acid (VPA) reduces epileptic attacks, inhibits the emergence of pathological form of plasticity in fast-spiking (FS) interneurons and restores physiological striatal synaptic plasticity in medium spiny (MS) neurons. Brain-derived neurotrophic factor (BDNF) is a key factor for the induction and maintenance of synaptic plasticity and it is also implicated in the mechanisms underlying epilepsy-induced adaptive changes. In this study, we explore the possibility that the TrkB/BDNF system is involved in the striatal modifications associated with the Bassoon gene (Bsn) mutation. In epileptic mice abnormal striatum-dependent learning was paralleled by higher TrkB levels and an altered distribution of BDNF. Accordingly, subchronic intrastriatal administration of k252a, an inhibitor of TrkB receptor tyrosine kinase activity, reversed behavioral alterations in Bsn mutant mice. In addition, in vitro manipulations of the TrkB/BDNF complex by k252a, prevented the emergence of pathological plasticity in FS interneurons. Chronic treatment with VPA, by reducing seizures, was able to rebalance TrkB to control levels favoring a physiological redistribution of BDNF between MS neurons and FS interneurons with a concomitant recovery of striatal plasticity. Our results provide the first indication that BDNF is involved in determining the striatal alterations occurring in the early-onset epileptic syndrome associated with the absence of presynaptic protein Bassoon.

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“…A possible endogenous mediator of Egr3 signaling in TLE has yet to be identified. Because brainderived neurotrophic factor (BDNF) mRNAs and protein are elevated during seizures in TLE patients (17,18) and in several animal models of TLE (19 -21), we used cultured primary hippocampal neurons to determine whether BDNF could be the seizure-induced signal that up-regulates GABRA4 transcription and down-regulates GABRA1.…”

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confidence: 99%

Brain-derived Neurotrophic Factor (BDNF)-induced Synthesis of Early Growth Response Factor 3 (Egr3) Controls the Levels of Type A GABA Receptorα4 Subunits in Hippocampal Neurons

Roberts

Lund

et al. 2006

Journal of Biological Chemistry

126

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Altered function of ␥-aminobutyric acid type A receptors (GABA A Rs) in dentate granule cells of the hippocampus has been associated with temporal lobe epilepsy (TLE) in humans and in animal models of TLE. Such altered receptor function (including increased inhibition by zinc and lack of modulation by benzodiazepines) is related, in part, to changes in the mRNA levels of certain GABA A R subunits, including ␣4, and may play a role in epileptogenesis. The majority of GABA A Rs that contain ␣4 subunits are extra-synaptic due to lack of the ␥2 subunit and presence of ␦. However, it has been hypothesized that seizure activity may result in expression of synaptic receptors with altered properties driven by an increased pool of ␣4 subunits. Results of our previous work suggests that signaling via protein kinase C (PKC) and early growth response factor 3 (Egr3) is the plasticity trigger for aberrant ␣4 subunit gene (GABRA4) expression after status epilepticus. We now report that brain derived neurotrophic factor (BDNF) is the endogenous signal that induces Egr3 expression via a PKC/MAPK-dependent pathway. Taken together with the fact that blockade of tyrosine kinase (Trk) neurotrophin receptors reduces basal GABRA4 promoter activity by 50%, our findings support a role for BDNF as the mediator of Egr3-induced GABRA4 regulation in developing neurons and epilepsy and, moreover, suggest that BDNF may alter inhibitory processing in the brain by regulating the balance between phasic and tonic inhibition.The type A ␥-aminobutyric acid (GABA) 5 receptor (GABA A R) is an integral ligand gated ion channel that mediates the majority of inhibition in the central nervous system. Being a hetero-oligomeric complex, it is composed of five membrane spanning subunits that are chosen from the products of 19 different genes (␣ 1-6 , ␤ 1-3 , ␥ 1-3 , ␦, ⑀, , 1-3 , and ). These genes are differentially transcribed during development and in various regions of the adult brain and spinal cord (1-5). Alteration in the function of GABA A Rs has been associated with a variety of diseases whose etiology leads to an imbalance between inhibition and excitation in specific populations of neurons (6 -8).For instance, changes in certain GABA A R subunit levels occur in dentate granule cells (DGCs) of both humans with temporal lobe epilepsy (TLE) and in animal models of TLE (6, 9). These molecular responses have been hypothesized to underlie persistent changes in GABA A R function associated with epileptogenesis. Most notably, individual DGCs display an elevation of ␣4 subunit mRNAs and a decrease in ␣1 (6). Receptors that contain ␣4 subunits have unique pharmacological properties that include heightened blockade of receptor function by zinc (11-13) and decreased benzodiazepine modulation (14). In addition, the majority of GABA A Rs that contain ␣4 subunits (co-assembled with a ␤ and ␦) are located extrasynaptically and mediate tonic GABA currents, while those containing ␣(1, 2, 3, or 5) without ␦ and with ␥2 are targeted to the synapse (1, 15). Although...

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Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y

Cited by 111 publications

References 23 publications

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

TrkB/BDNF-Dependent Striatal Plasticity and Behavior in a Genetic Model of Epilepsy: Modulation by Valproic Acid

Brain-derived Neurotrophic Factor (BDNF)-induced Synthesis of Early Growth Response Factor 3 (Egr3) Controls the Levels of Type A GABA Receptorα4 Subunits in Hippocampal Neurons

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