Regulating hippocampal hyperexcitability through <scp>GABAB</scp> Receptors

Lang, Min; Moradi-Chameh, Homeira; Zahid, Tariq; Gane, Jonathan; Wu, Chenggang; Valiante, Taufik A.; Zhang, Liang

doi:10.1002/phy2.278

Cited by 13 publications

(15 citation statements)

References 86 publications

(173 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although their results conflict with our result, it is likely to be due to the fact that their results focused on acute response that occurred within 30 min after irradiation at high dose (10 Gy) in both differentiated neurons and NSCs of DG. Also, some studies have reported that the seizures, one of adverse effects of radiotherapy, is caused by change of electrical impulse through the loss of GABA receptors or the abnormal increase of calcium ion channels [ 72 , 73 ]. From the results of this study and previous reports, it is possible that the abnormal changes of synaptic signaling may be associated with IR-induced brain injuries.…”

Section: Discussionmentioning

confidence: 99%

Ionizing Radiation Induces Altered Neuronal Differentiation by mGluR1 through PI3K-STAT3 Signaling in C17.2 Mouse Neural Stem-Like Cells

Eom

Park

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Most studies of IR effects on neural cells and tissues in the brain are still focused on loss of neural stem cells. On the other hand, the effects of IR on neuronal differentiation and its implication in IR-induced brain damage are not well defined. To investigate the effects of IR on C17.2 mouse neural stem-like cells and mouse primary neural stem cells, neurite outgrowth and expression of neuronal markers and neuronal function-related genes were examined. To understand this process, the signaling pathways including PI3K, STAT3, metabotrophic glutamate receptor 1 (mGluR1) and p53 were investigated. In C17.2 cells, irradiation significantly increased the neurite outgrowth, a morphological hallmark of neuronal differentiation, in a dose-dependent manner. Also, the expression levels of neuronal marker proteins, β-III tubulin were increased by IR. To investigate whether IR-induced differentiation is normal, the expression of neuronal function-related genes including synaptophysin, a synaptic vesicle forming proteins, synaptotagmin1, a calcium ion sensor, γ-aminobutyric acid (GABA) receptors, inhibitory neurotransmitter receptors and glutamate receptors, excitatory neurotransmitter receptors was examined and compared to that of neurotrophin-stimulated differentiation. IR increased the expression of synaptophysin, synaptotagmin1 and GABA receptors mRNA similarly to normal differentiation by stimulation of neurotrophin. Interestingly, the overall expression of glutamate receptors was significantly higher in irradiated group than normal differentiation group, suggesting that the IR-induced neuronal differentiation may cause altered neuronal function in C17.2 cells. Next, the molecular mechanism of the altered neuronal differentiation induced by IR was studied by investigating signaling pathways including p53, mGluR1, STAT3 and PI3K. Increases of neurite outgrowth, neuronal marker and neuronal function-related gene expressions by IR were abolished by inhibition of p53, mGluR-1, STAT3 or PI3K. The inhibition of PI3K blocked both p53 signaling and STAT3-mGluR1 signaling but inhibition of p53 did not affect STAT3-mGluR1 signaling in irradiated C17.2 cells. Finally, these results of the IR-induced altered differentiation in C17.2 cells were verified in ex vivo experiments using mouse primary neural stem cells. In conclusion, the results of this study demonstrated that IR is able to trigger the altered neuronal differentiation in undifferentiated neural stem-like cells through PI3K-STAT3-mGluR1 and PI3K-p53 signaling. It is suggested that the IR-induced altered neuronal differentiation may play a role in the brain dysfunction caused by IR.

show abstract

Section: Discussionmentioning

confidence: 99%

Ionizing Radiation Induces Altered Neuronal Differentiation by mGluR1 through PI3K-STAT3 Signaling in C17.2 Mouse Neural Stem-Like Cells

Eom

Park

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…GABA B Rs modulate network excitation [ 35 ] and especially NMDAR-depended activity [ 45 , 46 ]. The fact that blockade of GABA B Rs increased the proportion of slices that displayed either spfps or spfps -nmda , suggests that GABA B R-mediated transmission regulates the excitation threshold in the local circuitry as for example occurs in the subiculum [ 34 ] and control synchronous discharges [ 50 ]. Importantly, the present results show that GABA B Rs effectively control the overall network excitability in DH but not VH.…”

Section: Discussionmentioning

confidence: 99%

Higher intrinsic network excitability in ventral compared with the dorsal hippocampus is controlled less effectively by GABAB receptors

Papatheodoropoulos

2015

BMC Neurosci

View full text Add to dashboard Cite

BackgroundElucidating specializations of the intrinsic neuronal network between the dorsal and the ventral hippocampus is a recently emerging area of research that is expected to help us understand the mechanisms underlying large scale functional diversification along the hippocampus. The aim of this study was to characterize spontaneous network activity between the dorsal and the ventral hippocampus induced under conditions of partial or complete blockade of GABAergic inhibition (i.e. disinhibition).ResultsUsing field recordings from the CA3 and CA1 fields of hippocampal slices from adult rats I found that ventral compared with dorsal hippocampus slices displayed higher propensity for and higher frequency of occurrence of spontaneous field potentials (spfps) at every level of disinhibition. Also NMDA receptor-depended spfps (spfps-nmda) occurred with higher probability more frequently and were larger in the ventral compared with the dorsal hippocampus. Importantly, blockade of GABAB receptors produced a stronger effect in enhancing the probability of generation of spfps and spfps-nmda in the dorsal compared with the ventral hippocampal slices and increased spfps-nmda only in dorsal slices.ConclusionThese results demonstrate a higher intrinsic neuronal excitability of the ventral compared with the dorsal local circuitry with the considerable contribution of NMDA receptors. Furthermore, the GABAB receptors control the total and the NMDA receptor-dependent excitation much less effectively in the ventral part of the hippocampus. It is proposed that NMDA and GABAB receptors significantly contribute to differentiate local network dynamics between the dorsal and the ventral hippocampus with important implications in the information processing performed along the long hippocampal axis.

show abstract

“…Power spectral plots were generated by averaging with 50% window overlap and a spectral resolution of 0.3 Hz. EEG spikes were considered if they displayed amplitudes of ≥6 times of standard deviations of background EEG signals and base durations of 30-70 ms (Jeffrey et al, 2013;Lang et al, 2014). To determine the dominant frequency of the hippocampal theta rhythm, spectral plots were generated from 10-s EEG segments in individual mice during the period of movement or exploration behaviors.…”

Section: Eeg Recordings and Hippocampal Stimulationmentioning

confidence: 99%

“…2013; Lang et al, 2014), thus suggesting a subtle increase of hippocampal network excitability in some post-HI mice.…”

Section: Eeg Discharges Unobserved In Post-hi Micementioning

confidence: 99%

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

Peng

Arora

et al. 2015

Epilepsy Research

Self Cite

View full text Add to dashboard Cite

Regulating hippocampal hyperexcitability through GABAB Receptors

Cited by 13 publications

References 86 publications

Ionizing Radiation Induces Altered Neuronal Differentiation by mGluR1 through PI3K-STAT3 Signaling in C17.2 Mouse Neural Stem-Like Cells

Ionizing Radiation Induces Altered Neuronal Differentiation by mGluR1 through PI3K-STAT3 Signaling in C17.2 Mouse Neural Stem-Like Cells

Higher intrinsic network excitability in ventral compared with the dorsal hippocampus is controlled less effectively by GABAB receptors

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

Contact Info

Product

Resources

About