Increased expression of Sonic hedgehog in temporal lobe epileptic foci in humans and experimental rats

Fang, Min; Lü, Yang; Chen, Guojun; Shen, Lan; Pan, Yumin; Wang, X.-F.

doi:10.1016/j.neuroscience.2011.02.060

Cited by 30 publications

(19 citation statements)

References 26 publications

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“…Our novel findings of a prolonged increase in Shh expression in TMT+saline-treated groups is in line with previous evidence suggesting a relationship between Shh expression and TLE in both experimental models and human epilepsy [73], [74]. It has been hypothesised, in this regard, that the Shh pathway may be an important mechanism through which epilepsy enhances adult hippocampal neurogenesis [73].…”

Section: Discussionsupporting

confidence: 91%

“…Given that this pathway has been proposed to exert neuroprotective effects in many neurologic diseases [40], [75], [76], we may also hypothesise that the enhanced Shh expression during TMT-induced neurodegeneration could be part of the early activation of repair mechanisms in the injured hippocampus, albeit with no reparative outcome. On the other hand, a role in the development of neuronal death and TLE cannot be excluded, as suggested by other groups [74].…”

Section: Discussionmentioning

confidence: 92%

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The Neurogenic Effects of Exogenous Neuropeptide Y: Early Molecular Events and Long-Lasting Effects in the Hippocampus of Trimethyltin-Treated Rats

et al. 2014

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Modulation of endogenous neurogenesis is regarded as a promising challenge in neuroprotection. In the rat model of hippocampal neurodegeneration obtained by Trimethyltin (TMT) administration (8 mg/kg), characterised by selective pyramidal cell loss, enhanced neurogenesis, seizures and cognitive impairment, we previously demonstrated a proliferative role of exogenous neuropeptide Y (NPY), on dentate progenitors in the early phases of neurodegeneration. To investigate the functional integration of newly-born neurons, here we studied in adult rats the long-term effects of intracerebroventricular administration of NPY (2 µg/2 µl, 4 days after TMT-treatment), which plays an adjuvant role in neurodegeneration and epilepsy. Our results indicate that 30 days after NPY administration the number of new neurons was still higher in TMT+NPY-treated rats than in control+saline group. As a functional correlate of the integration of new neurons into the hippocampal network, long-term potentiation recorded in Dentate Gyrus (DG) in the absence of GABAA receptor blockade was higher in the TMT+NPY-treated group than in all other groups. Furthermore, qPCR analysis of Kruppel-like factor 9, a transcription factor essential for late-phase maturation of neurons in the DG, and of the cyclin-dependent kinase 5, critically involved in the maturation and dendrite extension of newly-born neurons, revealed a significant up-regulation of both genes in TMT+NPY-treated rats compared with all other groups. To explore the early molecular events activated by NPY administration, the Sonic Hedgehog (Shh) signalling pathway, which participates in the maintenance of the neurogenic hippocampal niche, was evaluated by qPCR 1, 3 and 5 days after NPY-treatment. An early significant up-regulation of Shh expression was detected in TMT+NPY-treated rats compared with all other groups, associated with a modulation of downstream genes. Our data indicate that the neurogenic effect of NPY administration during TMT-induced neurodegeneration involves early Shh pathway activation and results in a functional integration of newly-generated neurons into the local circuit.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 92%

The Neurogenic Effects of Exogenous Neuropeptide Y: Early Molecular Events and Long-Lasting Effects in the Hippocampus of Trimethyltin-Treated Rats

et al. 2014

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“…Western blotting was performed as previous report to detect the expression of adenosine A1 receptor in normal and epileptic rats [45]. The rats’ hippocampal tissues were stored in liquid nitrogen for western blotting analysis.…”

Section: Methodsmentioning

confidence: 99%

Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge of hippocampal neurons from epileptic rats

et al. 2017

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Nitrobenzylthioinosine (NBTI), a specific inhibitor of type 1 equilibrative nucleoside transporter, could regulate the extracellular adenosine concentration and have protective roles in seizures. However, the protection mechanism of NBTI in seizures remains poorly understood. Here, the expression pattern and subcellular distribution of adenosine A1 receptor were detected by Western blot analysis and double-labeling immunofluorescence staining in Lithium Chloride-Pilocarpine induced epileptic rat model. At 24 h after pilocarpine induced rat seizures, hippocampal slices were prepared and the evoked excitatory postsynaptic currents (eEPSCs) amplitude of pyramidal neurons in hippocampus CA1 region was recorded using whole-cell patch clamp. In vivo, compared to control group, Western blotting analysis showed that the expression of adenosine A1 receptor protein was increased at 24 h and 72 h after seizure, didn't change at 0 min and 1 w, and decreased at 2 w. Double-label immunofluorescence revealed that adenosine A1 receptor was mainly expressed in the membrane and cytoplasm of neurons. In Vitro, adenosine decreased the eEPSCs amplitude of pyramidal neurons in hippocampus CA1 region, NBTI also had the same effect. Meantime, NBTI could further inhibit eEPSCs amplitude on the basis of lower concentration adenosine (50μM), and adenosine A1 receptor inhibitor DPCPX partially reversed this effect. Taken together, we confirmed that the expression of adenosine A1 receptor protein was increased in the early seizures and decreased in the late seizures. At the same time, NBTI mimics adenosine to attenuate the epileptiform discharge through adenosine A1 receptor, which might provide a novel therapeutic approach toward the control of epilepsy.

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“…Six head trauma patients (4 males and 2 females; 25–45 years old) were used for comparative purposes in the electrocorticography because their temporal neocortexes were histologically normal. All of these patients had no history of epilepsy or exposure to antiepileptic drugs[56]. All of these patients or their immediate relatives signed written consent forms for the use of brain tissue.…”

Section: Materials Subjects and Methodsmentioning

confidence: 99%

Increased expression of Notch1 in temporal lobe epilepsy: animal models and clinical evidence

et al. 2014

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Temporal lobe epilepsy is associated with astrogliosis. Notch1 signaling can induce astrogliosis in glioma. However, it remains unknown whether Notch1 signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notch1, hairy and enhancer of split-1, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocarpine-treated rats. The presence of Notch1 and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalogram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notch1, hairy and enhancer of split-1, and glial fibrillary acidic protein were enhanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups: control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split-1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notch1 signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notch1 signaling.

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Increased expression of Sonic hedgehog in temporal lobe epileptic foci in humans and experimental rats

Cited by 30 publications

References 26 publications

The Neurogenic Effects of Exogenous Neuropeptide Y: Early Molecular Events and Long-Lasting Effects in the Hippocampus of Trimethyltin-Treated Rats

The Neurogenic Effects of Exogenous Neuropeptide Y: Early Molecular Events and Long-Lasting Effects in the Hippocampus of Trimethyltin-Treated Rats

Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge of hippocampal neurons from epileptic rats

Increased expression of Notch1 in temporal lobe epilepsy: animal models and clinical evidence

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