Short increase of BDNF messenger RNA triggers kainic acid-induced neuronal hypertrophy in adult mice

Guilhem, D.; Dreyfus, Patrick A.; Makiura, Yaeko; Suzuki, Fumio; Onténiente, Brigitte

doi:10.1016/0306-4522(96)00005-x

Cited by 36 publications

(24 citation statements)

References 43 publications

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“…We cannot rule out, however, that other factors are involved in the downregulation of reelin synthesis. We and others (Guilhem et al, 1996) have shown a long-lasting upregulation of BDNF expression in the dentate gyrus after KA injection. BDNF, in turn, is known to negatively regulate reelin synthesis during cortical development (Ringstedt et al, 1998), and it is important for GCD formation (Giulhem et al, 1996).…”

Section: Reelin Keeps Granule Cells In Registermentioning

confidence: 54%

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Heinrich¹,

Nitta²,

Flubacher³

et al. 2006

J. Neurosci.

279

308

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Mesio-temporal lobe epilepsy (MTLE) is often accompanied by granule cell dispersion (GCD), a widening of the granule cell layer. The molecular determinants of GCD are poorly understood. Here, we used an animal model to study whether GCD results from an increased dentate neurogenesis associated with an abnormal migration of the newly generated granule cells. Adult mice were given intrahippocampal injections of kainate (KA) known to induce focal epileptic seizures and GCD, comparable to the changes observed in human MTLE. Ipsilateral GCD progressively developed after KA injection and was paralleled by a gradual decrease in the expression of doublecortin, a marker of newly generated granule cells, in the dentate subgranular layer. Staining with Fluoro-Jade B revealed little cell degeneration in the subgranular layer on the KA-injected side. Labeling with bromodeoxyuridine showed an early, transient increase in mitotic activity in the dentate gyrus of the KA-injected hippocampus that gave rise to microglial cells and astrocytes but not to new neurons. Moreover, at later time points, there was a virtually complete cessation of mitotic activity in the injected hippocampus (where GCD continued to develop), but not on the contralateral side (where no GCD was observed). Finally, a significant decrease in reelin mRNA synthesis in the injected hippocampus paralleled the development of GCD, and neutralization of reelin by application of the CR-50 antibody induced GCD. These results show that GCD does not result from increased neurogenesis but reflects a displacement of mature granule cells, most likely caused by a local reelin deficiency.

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Section: Reelin Keeps Granule Cells In Registermentioning

confidence: 54%

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Heinrich¹,

Nitta²,

Flubacher³

et al. 2006

J. Neurosci.

279

308

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“…A major activity-dependent mechanism stimulated by intrahippocampal KA injection in this mouse model of TLE is the strong BDNF and TrkB overexpression, which is required for GCD to occur (Suzuki et al, 1995;Guilhem et al, 1996). Furthermore, BDNF has been shown to regulate reelin production (Ringstedt et al, 1998), at least during brain development.…”

Section: Sensitization Of Cajal-retzius Cells To Bdnfmentioning

confidence: 97%

Impaired reelin processing and secretion by Cajal–Retzius cells contributes to granule cell dispersion in a mouse model of temporal lobe epilepsy

et al. 2011

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Cajal-Retzius cells play a crucial role during ontogeny in regulating cortical lamination via release of reelin. In adult brain, they comprise small calretinin-positive interneurons located in the marginal zone of the cerebral cortex and in the hippocampal fissure. Alterations of reelin signaling or expression have been involved in major neurological disorders, and they underlie granule cell dispersion (GCD) in mesial temporal lobe epilepsy (TLE). Here, we investigated in a mouse model of TLE the contribution of Cajal-Retzius cells to reelin production in epileptic hippocampus and the molecular mechanisms underlying GCD. Following unilateral intrahippocampal Kainic acid injection in adult mice to induce an epileptic focus, we observed that Cajal-Retzius cells gradually became strongly immunopositive for reelin, due to intracellular accumulation. This phenotype resembled the morphology of Cajal-Retzius cells in reeler Orleans (reln (orl/orl) ) mice, which express a secretion-deficient 310-kDa reelin fragment. The possibility that GCD might result from abnormal reelin processing in Cajal-Retzius cells, leading to a lack of reelin secretion, was confirmed by KA injection in reln (orl/+) mice, which induced severe GCD. Furthermore, Western blot analysis in KA-treated wildtype mice revealed increased production of ∼300-kDa reelin fragments, confirming abnormal proteolytic processing. This effect was not seen upon treatment with Botulinum neurotoxin E (BoNT/E), which prevents GCD in KA-lesioned hippocampus by chronic blockade of synaptic transmission. Furthermore, BoNT/E blocked upregulation of TrkB in Cajal-Retzius cells, suggesting that production of truncated reelin in KA-treated hippocampus is activity-dependent and regulated by BDNF. Altogether, these data reveal that GCD results from abnormal reelin processing in Cajal-Retzius cells under the control of BDNF. Our findings highlight the critical role played by Cajal-Retzius cells for hippocampal neuronal reorganization in TLE.

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“…NGF was dissolved in PBS to prepare 0.5 g/l as described previously (Kent et al, 1999). K-252a was dissolved in 1 M PBS as described previously (Guilhem et al, 1996). We injected PBS as the vehicle for both NGF and K-252a.…”

Section: Methodsmentioning

confidence: 99%

“…8 A). We performed intraventricular injection of K-252a as previously reported (Guilhem et al, 1996) and confirmed that it effectively reduced NGF receptor activity. TUNEL-positive cells were reduced in the NGF-treated mice compared with the vehicle-treated mice 24 hr after tFCI, but they were increased in the K-252a-treated mice compared with the vehicle-treated animals at the same time point (n ϭ 4; Fig.…”

Section: Ppras Positivity Did Not Colocalize With Activated Caspase-3mentioning

confidence: 99%

Neuroprotective Role of a Proline-Rich Akt Substrate in Apoptotic Neuronal Cell Death after Stroke: Relationships with Nerve Growth Factor

Saito¹,

Narasimhan²,

Hayashi³

et al. 2004

J. Neurosci.

106

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The Akt signaling pathway contributes to regulation of apoptosis after a variety of cell death stimuli. A novel proline-rich Akt substrate (PRAS) was recently detected and found to be involved in apoptosis. In our study, Akt activation was modulated by growth factors, and treatment with nerve growth factor (NGF) reduced apoptotic cell death after ischemic injury. However, the role of the PRAS pathway in apoptotic neuronal cell death after ischemia remains unknown. Phosphorylated PRAS (pPRAS) and the binding of pPRAS/phosphorylated Akt (pPRAS/pAkt) to 14-3-3 (pPRAS/14-3-3) were detected, and their expression transiently decreased in mouse brains after transient focal cerebral ischemia (tFCI). Liposome-mediated pPRAS cDNA transfection induced overexpression of pPRAS, promoted pPRAS/14-3-3, and inhibited apoptotic neuronal cell death after tFCI. The expression of pPRAS, pPRAS/pAkt, and pPRAS/14-3-3 increased in NGF-treated mice but decreased with inhibition of phosphatidylinositol-3 kinase and the NGF receptor after tFCI. These results suggest that PRAS phosphorylation and its interaction with pAkt and 14-3-3 might play an important role in neuroprotection mediated by NGF in apoptotic neuronal cell death after tFCI.

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Short increase of BDNF messenger RNA triggers kainic acid-induced neuronal hypertrophy in adult mice

Cited by 36 publications

References 43 publications

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Impaired reelin processing and secretion by Cajal–Retzius cells contributes to granule cell dispersion in a mouse model of temporal lobe epilepsy

Neuroprotective Role of a Proline-Rich Akt Substrate in Apoptotic Neuronal Cell Death after Stroke: Relationships with Nerve Growth Factor

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