Pentylenetetrazol-induced seizures are exacerbated by sleep deprivation through orexin receptor-mediated hippocampal cell proliferation

Ni, Li; Zhu, Mei; Yun, Seok-Kweon; Liu, Xiao Min; Ji, Tang

doi:10.1007/s10072-013-1495-5

Cited by 18 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement, it was demonstrated that intrahippocampal injection of SB‐334867 decreased rat seizures following acute PTZ injection . In another study, SB‐334867 not only had protective effects on PTZ‐induced seizures in sleep‐deprived rats, but also reduced the damage to the hippocampal CA3 neurons . Similar anti‐epileptic effects have been reported by Socala and co‐workers in a very recent study .…”

Section: Discussionsupporting

confidence: 83%

“…The study comprised six different groups as follows: control group (vehicle solution, 2 μL/rat), valproate group (26 μg/rat), and SB‐334867‐treated groups (2.5, 5, and 10 μg/rat). The doses for SB‐334867 and valproate were selected according to the previous studies . An extra group of animals received saline (2 μL/rat, ICV), and after 30 min, saline was injected IP.…”

Section: Methodsmentioning

confidence: 99%

“…For induction of kindling, PTZ (32 mg/kg) was injected IP every other day for 24 days [15]. Thirty min before administration of PTZ, the rats received ICV injections [16,17]. An extra group of animals received saline (2 lL/rat, ICV), and after 30 min, saline was injected IP.…”

Section: Experimental Designmentioning

confidence: 99%

See 2 more Smart Citations

SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats

Jaz

Moghimi

Fereidoni

et al. 2016

Fundam Clin Pharmacol

View full text Add to dashboard Cite

Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol (PTZ)-kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two-day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB-334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure-related behaviors were monitored for 30 min following PTZ administration. The anxiety-like behaviors were also assessed using elevated plus-maze in the first and last days of the study. The results revealed that ICV injection of SB-334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ-induced anxiety-like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats

Jaz

Moghimi

Fereidoni

et al. 2016

Fundam Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…Whether these changes worsen as DS mice approach death has yet to be determined. Interestingly, the number of animals that survived pentylenetetrazol (PTZ) injections and subsequent seizures positively correlated with previous sleep; sleep deprivation increased mortality and restored sleep improved survivability . These data suggest that restored sleep may improve ability to recover from a severe seizure.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of rest deficiency precedes sudden death of epileptic Kv1.1 knockout mice, a model of sudden unexpected death in epilepsy

et al. 2017

View full text Add to dashboard Cite

SummaryObjective: Chronic sleep deficiency is associated with early mortality. In the epileptic population, there is a higher prevalence of sleep disorders, and individuals with severe refractory epilepsy are at greater risk of premature mortality than the general population. Sudden unexpected death in epilepsy affects 1:1000 cases of epilepsy each year. Ketogenic diet (KD) treatment is one of the few effective options for refractory seizures. Despite KD reducing seizures and increasing longevity in Kv1.1 knockout (KO) mice, they still succumb to sudden death. This study aims to determine whether (1) the rest profiles of KO and KD-treated KO (KOKD) mice resemble each other as a function of either age or proximity to death and (2) the timing of death correlates with acute or chronic changes in rest. Methods: Noninvasive actimetry was used to monitor rest throughout the lives of KO and wild-type (WT) littermates administered standard diet or KD. Results: As KO mice age, rest is reduced (P < .0001). Rest is significantly improved in KDKO mice (P < .0001), resembling WT values at several ages. When age is removed as a variable and data are realigned to the day of death, the rest profiles of KO and KOKD groups worsen to similar degrees as a function of proximity to death. The amount of rest acutely is not sensitive to the timing of death, whereas chronic rest deficiency profiles (10-15 days prior to death) of both groups were indistinguishable. Chronic accumulation of rest deficiency over the final 15 days was associated with 75% of deaths. Significance: Our data suggest that the accumulated rest deficiency is associated with sudden death in Kv1.1 KO mice. These data (1) support the proposed clinical hypothesis that chronic sleep deficiency may be associated with early mortality in epileptic patients and (2) warrant future preclinical and clinical studies on sleep monitoring in epileptic patients. K E Y W O R D Sepilepsy, ketogenic diet, Kv1.1 knockout, sleep disorders, sudden unexpected death in epilepsy,

show abstract

“…In addition, hippocampal neuronal degeneration due to sleep deprivation‐induced epileptical seizures is amplified by the action of orexins (Ni et al . ).…”

Section: Discussionmentioning

confidence: 97%

Diurnal inhibition of NMDA‐EPSCs at rat hippocampal mossy fibre synapses through orexin‐2 receptors

Perin

Longordo

Massonnet

et al. 2014

The Journal of Physiology

View full text Add to dashboard Cite

Key pointsr Orexins are well described for their excitatory actions on feeding-and arousal-promoting brain centres; we describe here an inhibitory action of orexin-A on synaptic NMDA receptors in hippocampus, a key area for synaptic plasticity and memory formation.r Orexin-A inhibited NMDA receptor responses at mossy fibre-CA3 connections through postsynaptically expressed orexin-2 receptors, whereas a minor inhibition was observed at Schaffer collateral-CA1 connections, and no effect occurred at non-mossy-fibre excitatory synapses in CA3.r Exogenously applied orexin-A inhibited NMDA receptors in slices prepared during the rats' resting phase, when endogenous orexin levels are low, but not in slices prepared in the active phase, when endogenous orexins peak.r Through intraperitoneal administration of an orexin receptor antagonist during the active period, exogenous orexin-A-mediated inhibition was restored in the slice.r Endogenous orexins suppress hippocampal synaptic NMDA receptor function in a diurnally cyclic manner, probably restraining synaptic plasticity and learning during certain periods of waking.Abstract Diurnal release of the orexin neuropeptides orexin-A (Ox-A, hypocretin-1) and orexin-B (Ox-B, hypocretin-2) stabilises arousal, regulates energy homeostasis and contributes to cognition and learning. However, whether cellular correlates of brain plasticity are regulated through orexins, and whether they do so in a time-of-day-dependent manner, has never been assessed. Immunohistochemically we found sparse but widespread innervation of hippocampal subfields through Ox-A-and Ox-B-containing fibres in young adult rats. The actions of Ox-A were studied on NMDA receptor (NMDAR)-mediated excitatory synaptic transmission in acute hippocampal slices prepared around the trough (Zeitgeber time (ZT) 4-8, corresponding to 4-8 h into the resting phase) and peak (ZT 23) of intracerebroventricular orexin levels. At ZT 4-8, exogenous Ox-A (100 nM in bath) inhibited NMDA receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) at mossy fibre (MF)-CA3 (to 55.6 ± 6.8% of control, P = 0.0003) and at Schaffer collateral-CA1 synapses (70.8 ± 6.3%, P = 0.013), whereas it remained ineffective at non-MF excitatory synapses in CA3. Ox-A actions were mediated postsynaptically and blocked by the orexin-2 receptor (OX2R) antagonist JNJ10397049 (1 μM), but not by orexin-1 receptor inhibition (SB334867, 1 μM) or by adrenergic and cholinergic antagonists. At ZT 23, inhibitory effects of exogenous Ox-A were absent (97.6 ± 2.9%, P = 0.42), but reinstated (87.2 ± 3.3%, P = 0.002) when endogenous orexin signalling was attenuated for 5 h through I.P. injections of almorexant (100 mg kg −1 ), a dual orexin receptor antagonist. In conclusion, endogenous orexins modulate hippocampal NMDAR function in a time-of-day-dependent manner, suggesting that they may influence cellular plasticity and consequent variations in memory performance across the sleep-wake cycle.

show abstract

Pentylenetetrazol-induced seizures are exacerbated by sleep deprivation through orexin receptor-mediated hippocampal cell proliferation

Cited by 18 publications

References 34 publications

SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats

SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats

Accumulation of rest deficiency precedes sudden death of epileptic Kv1.1 knockout mice, a model of sudden unexpected death in epilepsy

Diurnal inhibition of NMDA‐EPSCs at rat hippocampal mossy fibre synapses through orexin‐2 receptors

Contact Info

Product

Resources

About