Neuroprotective effects of leptin following kainic acid-induced status epilepticus

Obeid, Makram; Frank, J. Howard; Médina, Margarita; Finckbone, VelvetLee; Bliss, Richard; Bista, Binod; Majmudar, Shirine; Hurst, Daniel J.; Strahlendorf, Howard K.; Strahlendorf, Jean C.

doi:10.1016/j.yebeh.2010.07.023

Cited by 40 publications

(29 citation statements)

References 23 publications

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“…JAK2 dependent regulation of glutamate transporters may contribute to the cerebral effects of leptin, which Kawakami protects against hypoxic neuronal injury [92] and excitotoxicity as well as seizures under a variety of conditions [2,3,93]. JAK2-dependent upregulation of glutamate transporters may further participate in the protective effect of erythropoeitin against excitotoxicity [6,94].…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Glutamate Transporters by JAK2

Hosseinzadeh

Bhavsar²,

Sopjani³

et al. 2011

Cell Physiol Biochem

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The Janus-activated kinase-2 JAK2 is involved in the signaling of leptin and erythropoietin receptors and mediates neuroprotective effects of the hormones. In theory, JAK2 could be effective through modulation of the glutamate transporters, carriers accounting for the clearance of glutamate released during neurotransmission. The present study thus elucidated the effect of JAK2 on the glutamate transporters EAAT1, EAAT2, EAAT3 and EAAT4. To this end, cRNA encoding the carriers was injected into Xenopus oocytes with or without cRNA encoding JAK2 and glutamate transport was estimated from glutamate induced current (I_glu). I_glu was observed in Xenopus oocytes expressing EAAT1 or EAAT2 or EAAT3 or EAAT4, but not in water injected oocytes. Coexpression of JAK2 resulted in an increase of I_glu by 83% (EAAT1), 67% (EAAT2), 42% (EAAT3) and 126% (EAAT4). As shown for EAAT4 expressing Xenopus oocytes, the effect of JAK2 was mimicked by gain of function mutation ^V617FJAK2 but not by the inactive mutant ^K882EJAK2. Incubation with JAK2 inhibitor AG490 (40 µM) resulted in a gradual decrease of I_glu by 53%, 79% and 92% within 3, 6 and 24 hours. Confocal microscopy and chemiluminescence analysis revealed that JAK2 coexpression increased EAAT4 protein abundance in the cell membrane. Disruption of transcription did not appreciably modify the up-regulation of I_glu in EAAT4 expressing oocytes. The decay of I_glu following inhibition of carrier insertion with brefeldin A was similar in oocytes expressing EAAT4 + JAK2 and oocytes expressing EAAT4 alone, indicating that JAK2 did not appreciably affect carrier retrieval from the membrane. In conclusion, JAK2 is a novel powerful regulator of glutamate transporters and thus participates in the protection against excitotoxicity.

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Section: Discussionmentioning

confidence: 99%

Regulation of the Glutamate Transporters by JAK2

Hosseinzadeh

Bhavsar²,

Sopjani³

et al. 2011

Cell Physiol Biochem

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“…Adult rats which had received leptin had a significantly larger pyramidal cell surface area and fewer degenerated neurons. 24 The liver glycogen content in intermittently fasting male and female golden hamsters increased after 6 weeks of intermittent fasting with access to food for 3 days a week. 25 Serum interleukin-6 and C-reactive protein levels were significantly reduced after 3 weeks of a PF-diet in fasting humans of both genders.…”

Section: Discussionmentioning

confidence: 99%

Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats

Karimzadeh

Jafarian

Gharakhani

et al. 2013

Nutritional Neuroscience

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These results support the idea that a PF-diet has anticonvulsive and neuroprotective effects on epileptic rats but underlines that different PF-diet protocols can have varying effects. Anticonvulsive effects were strongest when the PF-diet started before the onset of excitotoxic injuries, the number of dark neurons was decreased and apoptosis was prevented by all PF-diet protocols investigated in this work. Further evaluation of PF-diet protocols for possible clinical anticonvulsant and neuroprotective effects is suggested.

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“…These seizures propagate to other limbic structures and its region-specific neuropathological changes in hippocampus are comparable to those of patients with chronic temporal lobe epilepsy (TLE) (Ben-Ari & Cossart, 2000; Obeid et al, 2010; Laurén Lopez-Picon, Brandt, Rios-Rojas, & Holopainen, 2010; Sloviter, Zappone, Harvey, & Frotscher, 2006). …”

Section: Introductionmentioning

confidence: 94%

The Effects of Kainic Acid-Induced Seizure on Gene Expression of Brain Neurotransmitter Receptors in Mice Using RT2 PCR Array

Farivar

Nassiri‐Asl

Johari

et al. 2016

BCN

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Introduction:Kainic acid (KA) induces neuropathological changes in specific regions of the mouse hippocampus comparable to changes seen in patients with chronic temporal lobe epilepsy (TLE). According to different studies, the expression of a number of genes are altered in the adult rat hippocampus after status epilepticus (SE) induced by KA. This study aimed to quantitatively evaluate changes in the gene expression of brain neurotransmitter receptors one week after administration of kainic acid in the mouse hippocampus.Methods:We used 12 BALB/c mice in this study and randomly divided them into 2 groups. To both groups, saline (IP) was administered for 7 days, and on the last day, KA (10 mg/kg, IP) was injected 30 minutes after administration of saline. Subsequently, behavioural changes were observed in mice. Then, in one group (1 day group), 2 hours and in another group (7 days group), 7 days after KA administration, the hippocampus tissue of mice was removed and used for gene expression analyses. Total brain RNA was isolated and reversely transcribed. We performed qPCR using RT2 Profiler TMPCR Array Mouse Neurotransmitter Receptors and Regulators (QIAGEN) containing primers for 84 genes. In this regard, we selected 50 related genes for KA model.Results:Our results showed significant changes in the gene expression of GABAA subunits receptors, including α1-α3, α5, α6, β2, β3, γ1, ρ, and rho1-2 on day 7 compared with the day 1.Conclusion:Expression of both inhibitory and excitatory receptors changed after one week. Further studies are needed to find more molecular changes in the gene expression of brain neurotransmitter receptors and regulators over longer periods of time in KA models using RT2 PCR array.

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Neuroprotective effects of leptin following kainic acid-induced status epilepticus

Cited by 40 publications

References 23 publications

Regulation of the Glutamate Transporters by JAK2

Regulation of the Glutamate Transporters by JAK2

Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats

The Effects of Kainic Acid-Induced Seizure on Gene Expression of Brain Neurotransmitter Receptors in Mice Using RT2 PCR Array

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