Hippocampal orexin receptors: Localization and function.

Orexin (hypocretin) is secreted from the perifornical/lateral hypothalamus and is well known for sleep regulation. Orexin has two, orexin A and B, transcripts and two receptors, type 1 and 2 (OX1R and OX2R), located in the plasma membrane of neurons in different brain areas, including the hippocampus involved in learning, memory, seizures, and epilepsy, as physiologic and pathologic phenomena. OX1R is expressed in the dentate gyrus and CA1 and the OX2R in the CA3 areas. Orexin enhances learning and memory as well as reward, stress, seizures, and epilepsy, partly through OX1Rs, while either aggravating or alleviating those phenomena via OX2Rs. OX1Rs activation induces long-term changes of synaptic responses in the hippocampus, an age and concentration-dependent manner. Briefly, we will review the localization and functions of hippocampal orexin receptors, their role in learning, memory, stress, reward, seizures, epilepsy, and hippocampal synaptic plasticity.

Evaluating the role of astrocytes on ß-estradiol effect on seizures of Pilocarpine epileptic model.

Epilepsy with periodic and unpredictable seizures is associated with hippocampal glutamate toxicity and tissue reorganization. Astrocytes play an important role in mediating the neuroprotective effects of estradiol and reducing seizure severity. Accordingly, the protective effects of low and high doses of estradiol on behavioral, astrocytic involvement and neuronal survival aspects of Pilocarpine-induced epilepsy were investigated. Lithium- Pilocarpine (30mg/kg) model was used to provoke epilepsy. Βeta-estradiol (2,40µg/µl) was injected subcutaneously from 48 before to 48h after seizure induction. Behavioral convulsions were then monitored and recorded on the day of induction. Four weeks later, glutamine synthetase (GS) activity and the astrocyte transporter GLT-1 expression of the hippocampus were measured. Moreover, hippocampal glutamate and GABA were evaluated to study excitability changes. Finally, neuronal counting in the hippocampus was also performed using Nissl staining. The latency for generalized clonic (GC) convulsions significantly increased while the rate of GC and death significantly reduced due to ß-estradiol treatment. GS activity and GLT-1 expression increased in the groups receiving the high dose of ß-estradiol and Pilocarpine. Furthermore, the amount of both GABA and glutamate content decreased due to high dose of estradiol, while only GABA increased in Pilocarpine treated rats. Finally, administration of ß-estradiol with low and high doses increased and improved the density of nerve cells. It is concluded that chronic administration ß-estradiol has anticonvulsant and neuroprotective properties which are plausibly linked to astrocytic activity.