Research

Stress induced cognitive impairments

Orexinergic system involvement in stress effect

Epilepsy as a comorbidity of stress

Interests

  • Stress
  • Epilepsy
  • Learning and Memory

Laboratory Personel

Mahsa Nafari

Mahsa Nafari

Expert

Selected Theses

  • The Effect of lateral hypothalamus and orexin on pentylenetetrazol induced seizures in male rat

    Master Thesis by Nasibe Akbari

    Kindling is a model of epilepsy which results in changes of synaptic plasticity due to repetitive electrical or chemical stimulation of brain. lateral hypothalamus changes brain and hippocampal excitability and hence, the plasticity by activating orexinergic system which is primarily involved in sleep and wakefulness. We investigated the involvement of lateral hypothalamus (LH) and orexin in epileptogenesis and seizure by pentylenetetrazol (PTZ) kindling.

    Each male wistar rat received 45 mg/kg PTZ up to 13 (i.p) injections. Lidocaine was used to inactivate LH. Convulsive behavior was rated as an index of kindling hippocampal. Glutamate content was measured by an assay kit. Fixed brains was sliced and stained by cresyl violet to observe any histological change.

    PTZ injections resulted in kindling and decreased hippocampal glutamate content, while LH inactivation prevented PTZ kindling, but could not compensate glutamate content. Orexin receptor blocking prevented tonic clonic convulsion while orexin receptor stimulation only partially prevented tonic clonic convulsions. In parallel, orexin receptor blocking increased while stimulation decreased glutamate content. Cresyl violet staining showed a reduction in neuronal density in CA3 and hilar area of hippocampus of PTZ kindled animals compared to control groups, which did not return to normal state even after LH inactivation using liocaine.

    It is plausible that orexin effect on PTZ kindling depend on route of administration. It can be pro-convulsive when activate orexinergic modulatory system and affect hippocampal circuitry. In contrast, i.c.v injection can reduce PTZ convulsion probably through employing other neural pathways.

  • Evaluation the effect of hippocampal orexin receptors in hippocampal glutamate and GABA content following PTZ induced seizure in male rat

    Master Thesis by Elham Goudarzi

    Introduction: Orexin has been shown to implicate in a number of physiological and behavioral processes including, feeding and metabolism, reward pathways, nociception and anxiety behaviors. Orexin affect the neuronal excitability leading to epileptic activity. Distribution of orexin receptors in the hippocampus, as the main epilepsy involved center in temporal lobe, suggest the probable importance of orexin in seizure generation. In this study, the effect of hippocampal orexin 1 and 2 receptor on seizure and glutamate and GABA content were explored.
    Materials and methods: Orexin 1 receptor (OX1R) antagonist (SB-334867) and OX2R antagonist (TCS-OX2-29) administrated bilaterally through a seperate cannulae into both hippocampi. Intravenous PTZ application model was used to generate behavioral convulsion. Then, the amount of total hippocampal glutamate and GABA content were measured by biochemical method.
    Result: Oxr1 antagonist (SB), 50 nmol reduced seizure stage and duration, decreased glutamate while increased GABA content. SB [200] nmol also reduced seizure stage, duration and glutamate content, but GABA content was not changed. Oxr2 antagonist (TCS), 20 nmol reduced seizure satge and duration without concomitant change in glutamate and GABA content. TCS [40] nmol did not affect seizure and GABA content, while decreased glutamate content. Coadministration of SB [50], TCS [40] nmol and also SB [200], TCS [40] reduce seizure stage, duration and glutamate content, but increased GABA content.
    Conclusion: It is concluded that Oxr1 antagonist reduce seizure intensity and glutamate content, while increase GABA content. Oxr2 antagonist showed more prominent anticonvulsive property in lower concentration and decrease glutamate content in the higher dose. all together, orexin receptor antagonist show anticonvulsive property and suggest a likely role for then in controlling seizures.

  • Evaluation the effect of posterior hypothalamus glutamatergic receptor and orexinergic receptor-2 in pentylenetetrazol induced seizure control in male rat

    Master Thesis by Atieh Arzhang

    Introduction: Seizures are epileptic manifestations affected 1% of population worldwide. Orexins secreted from hypothalamic lateral area (LHA) are shown to be pro-convulsant, while histamine from neurons located in posterior hypothalamus (PH) has anticonvulsant effect. Glutamate receptor (GluR) and orexin receptor 2 (OX2R) are located on PH histaminergic neurons that receive orexinergic fibers from LHA. Therefore, we investigate the importance of the interconnection and the role of OX2R in PH anticonvulsant effect.

    Materials and methods: Histidine (His; 1500 mg/kg) (i.p. injection), Orexin 2 receptor (OX2R) antagonist (TCS-OX2-29; 40 nmol), Glutamate receptor (GluR) antagonist (CNQX; 3 mM) and Glutamate (Glu; 1 mM) injected bilaterally into PH using stereotaxic surgery. Intravenous PTZ infusion model was used to generate behavioral convulsions.

     

    Results: In this study were observed a significant reduction of stages and duration of convulsions, disappearance of tonic-clonic (T-C) convulsions and increase of infused PTZ volume to onset the first signs of seizures due to histidine treatment. Although blocking OX2Rs and/or Glu receptor of PH reduced seizure stages comparing to PTZ treatment, but it was increased compared with histidine treatment. Further, receptors blocking revealed T-C seizures and even increased the duration of these convulsions compared to PTZ application group. Interestingly, applying glutamate decreased T-C duration and showed anticonvulsive effect.

     

    Conclusions:

    Our data demonstrate that OX2R has significant role, beside glutamate receptors, on PH anticonvulsant effect. Therefore, OX2Rs could be suitable candidate to be concentrated in future studies on its anticonvulsive effects.

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  • Sample Project Title

    Very short description of the project.

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