The Role of Brain-Derived Neurotrophic Factor in Epileptogenesis: an Update

Wang, Xinyi; Hu, Zhe

doi:10.3389/fphar.2021.758232

Cited by 21 publications

(12 citation statements)

References 64 publications

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“…BDNF is crucial for the central nervous system development, and studies show that it is involved in epileptogenesis. Although there are contradictory data, some studies indicate that higher levels of BDNF induce epilepsy 39 . MECP2 is a methyl-CpG-binding protein important for appropriate neuronal development.…”

Section: Discussionmentioning

confidence: 99%

Cdkl5 mutant zebrafish shows skeletal and neuronal alterations mimicking human CDKL5 deficiency disorder

Varela

Martins

et al. 2022

Sci Rep

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CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental condition characterized primarily by seizures and impairment of cognitive and motor skills. Additional phenotypes include microcephaly, dysmorphic facial features, and scoliosis. Mutations in cyclin-dependent kinase-like 5 (CDKL5) gene, encoding a kinase essential for normal brain development and function, are responsible for CDD. Zebrafish is an accepted biomedical model for the study of several genetic diseases and has many advantages over other models. Therefore, this work aimed to characterize the phenotypic, behavioral, and molecular consequences of the Cdkl5 protein disruption in a cdkl5 mutant zebrafish line (sa21938). cdkl5sa21938 mutants displayed a reduced head size, suggesting microcephaly, a feature frequently observed in CDD individuals. Double staining revealed shorter craniofacial cartilage structures and decrease bone mineralization in cdkl5 homozygous zebrafish indicating an abnormal craniofacial cartilage development and impaired skeletal development. Motor behavior analysis showed that cdkl5sa21938 embryos had less frequency of double coiling suggesting impaired glutamatergic neurotransmission. Locomotor behavior analysis revealed that homozygous embryos swim shorter distances, indicative of impaired motor activity which is one of the main traits of CCD. Although no apparent spontaneous seizures were observed in these models, upon treatment with pentylenetetrazole, seizure behavior and an increase in the distance travelled were observed. Quantitative PCR showed that neuronal markers, including glutamatergic genes were dysregulated in cdkl5sa21938 mutant embryos. In conclusion, homozygous cdkl5sa21938 zebrafish mimic several characteristics of CDD, thus validating them as a suitable animal model to better understand the physiopathology of this disorder.

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Section: Discussionmentioning

confidence: 99%

Cdkl5 mutant zebrafish shows skeletal and neuronal alterations mimicking human CDKL5 deficiency disorder

Varela

Martins

et al. 2022

Sci Rep

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“…The neurotrophin BDNF is widely distributed in the CNS being involved in neuronal survival and differentiation during development and modulating neuronal synaptic strength in adulthood [54]. BDNF is upregulated in the hippocampus during epileptogenesis and interference with BDNF signaling pathway inhibited epileptogenesis in animal models [55]. Other researchers, however, provided evidence that provision of BDNF suppresses seizures and hippocampal neuronal loss in experimental epilepsy [56].…”

Section: Discussionmentioning

confidence: 99%

“…Herein, levels of BDNF decreased in brain of PTZ-treated rats and showed further significant and dose-dependent decrease after treatment with BBG. Since BDNF increases neuronal excitability [55], there is an intriguing possibility that this effect of BBG is of relevance to its seizure suppressive action.…”

Section: Discussionmentioning

confidence: 99%

Inhibition Of Pentylenetetrazole-Induced Seizures And Neuronal Injury By Brilliant Blue G: Role Of Oxidative Stress, And Brain Derived Neurotrophic Factor

et al. 2022

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We aimed to investigate the effect of the P2X7 purinergic receptor antagonist brilliant blue G (BBG) on epileptic seizures, brain oxidative stress and neuronal injury induced in rats by pentylenetetrazole (PTZ). Rats received repeated intraperitoneal (i.p) injections of PTZ till the development of status epilepticus. BBG (50 or 100 mg/kg) was i.p. administered 30 minutes before starting PTZ injections. Seizure scores, the latency time and the PTZ dose for each group required to reach status epilepticus were determined. Brain kevels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), paraoxonase-1 (PON-1), brain derived neurotrophic factor (BDNF), interleukin-6 (IL-6) and chemerin were determined and histopathological examination done. PTZ induced significant increases in brain MDA and NO by 72.5% and 194.1%, respectively compared with the saline control. GSH, PON-1 activity and BDNF decreased by 41.4%, 39.8% and 33.4% while IL-6 and chemerin increased by 13.3% and 26.8%. The PTZ-induced changes in MDA, NO, GSH and PON-1 were significantly reduced by treatment with BBG which also significantly decreased IL-6 and BDNF levels. BBG (50 or 100 mg/kg) decreased the mean total seizure score by 82% and 87%, respectively. Scores for myoclonic jerks were reduced by 94.0% and 97.6% and that for generalized tonic-clonic seizures by 75%. BBG increased the threshold dose of PTZ by 66.7% and 106.7% and the latency time for status epilepticus by 118%. BBG exerts anticonvulsant and neuroprotective effects, at least in part by decreasing brain oxidative stress, BDNF and neuroinflammation.

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“…Several in vitro, ex vivo, and in vivo studies suggest an involvement of BDNF in the pathophysiology of epilepsy [ 56 ]. However, two controversial views (BDNF inhibits or promotes epileptogenesis) still exist [ 57 ]. This discrepancy is most probably related to different role of BDNF in specific types of epilepsy and epileptogenesis and different expression and functions of BDNF in specific brain regions during the time course of epilepsy development [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

Дружкова

Yakovlev

Rider

et al. 2022

IJMS

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Background: The hypothalamic-pituitary-adrenal (HPA) axis, inflammatory processes and neurotrophic factor systems are involved in pathogenesis of both epilepsy and depressive disorders. The study aimed to explore these systems in patients with focal epilepsy (PWE, n = 76), epilepsy and comorbid depression (PWCED n = 48), and major depressive disorder (PWMDD, n = 62) compared with healthy controls (HC, n = 78). Methods: Parameters of the HPA axis, neurotrophic factors, and TNF-α were measured in blood serum along with the hemogram. Results: Serum cortisol level was augmented in PWE, PWCED, and PWMDD compared with HC and was higher in PWMDD than in PWE. Serum cortisol negatively correlated with Mini–Mental State Examination (MMSE) score in PWE, and positively with depression inventory–II (BDI-II) score in PWMDD. Only PWMDD demonstrated elevated plasma ACTH. Serum TNF-α, lymphocytes, and eosinophils were augmented in PWMDD; monocytes elevated in PWE and PWCED, while neutrophils were reduced in PWE and PWMDD. Serum BDNF was decreased in PWE and PWCED, CNTF was elevated in all groups of patients. In PWE, none of above indices depended on epilepsy etiology. Conclusions: The results confirm the involvement of HPA axis and inflammatory processes in pathogenesis of epilepsy and depression and provide new insights in mechanisms of epilepsy and depression comorbidity.

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The Role of Brain-Derived Neurotrophic Factor in Epileptogenesis: an Update

Cited by 21 publications

References 64 publications

Cdkl5 mutant zebrafish shows skeletal and neuronal alterations mimicking human CDKL5 deficiency disorder

Cdkl5 mutant zebrafish shows skeletal and neuronal alterations mimicking human CDKL5 deficiency disorder

Inhibition Of Pentylenetetrazole-Induced Seizures And Neuronal Injury By Brilliant Blue G: Role Of Oxidative Stress, And Brain Derived Neurotrophic Factor

Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

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