TRPV1 receptors augment basal synaptic transmission in CA1 and CA3 pyramidal neurons in epilepsy.

Temporal lobe epilepsy in human and animals is attributed to alterations in brain function especially hippocampus formation. Changes in synaptic activity might be causally related to the alterations during epileptogenesis. Transient receptor potential vanilloid 1 (TRPV1) as one of the non-selective ion channels has been shown to be involved in synaptic transmission. However, the potential role of TRPV1 receptors in synaptic function in the epileptic brain needs to be elucidated. In the present study, we used quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry to assess hippocampal TRPV1 mRNA expression, protein content, and distribution. Moreover, the effects of pharmacologic activation and inhibition of TRPV1 receptors on the slope of evoked field excitatory postsynaptic potentials (fEPSPs) were analyzed in CA1 and CA3 pyramidal neurons, after 3months of pilocarpine-induced status epilepticus (SE). SE induced an upregulation of TRPV1 mRNA and protein content in the whole hippocampal extract, as well as its distribution in both CA1 and CA3 regions. Activation and inhibition of TRPV1 receptors (via capsaicin 1µM and capsazepine 10µM, respectively) did not influence basal synaptic transmission in CA1 and CA3 regions of control slices, however, capsaicin increased and capsazepine decreased synaptic transmission in both regions in tissues from epileptic animals. Taken together, these findings suggest that a higher expression of TRPV1 in the epileptic condition is accompanied by alterations in basal synaptic transmission.

Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology.

Amyloid beta (Aß) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD) by changing the neuronal excitability. However, the cellular mechanisms by which accumulation of Aß affects intrinsic neuronal properties are not well understood. The effect of bilateral intra-frontal cortex Aß (1-42) peptide injection on the intrinsic excitability of hippocampal CA1 pyramidal neurons with particular focus on the contribution of hyperpolarization-activated (Ih) channel currents was examined using whole-cell patch-clamp recording. Passive avoidance memory impairment and morphological changes in rats receiving intra-frontal Aß treatment were observed, which was associated with significant changes both in passive and active intrinsic electrical membrane properties of CA1 pyramidal neurons. Electrophysiological recording showed a significant decrease in neuronal excitability associated with an augmentation in the first spike after-hyperpolarization (AHP) amplitude. In addition, the depolarizing sag voltage was altered in neurons recorded from Aß-treated group. In voltage-clamp condition, a hyperpolarizing activated inward current sensitive to ZD7288 and capsaicin was significantly increased in neurons from Aß-treated rats. The Ih current density was increased and the activation curve was shifted toward less negative potential in the Aß-treated group as compared to control group. The enhancing effect of Aß treatment on Ih current was confirmed by showing upregulation of the mRNA of HCN1 channel in the CA1 pyramidal layer of hippocampi. These findings suggest the contribution of Ih and possibly TRPV1 channel currents to the changes induced by Aß treatment in the intrinsic membrane properties, which, in turn, may provide therapeutic targets for treatment of AD.

The effect of L-arginine on Morris water maze tasks of ovariectomized rats.

The role of ovarian hormones, nitric oxide, and their interaction on learning and memory has been widely investigated. The present study was carried out to evaluate the effect of acute (A) and chronic (C) L-arginine (L-Arg) administration on learning and memory in ovariectomized (OVx) rats. Forty-five rats were divided into six groups: 1) sham, 2) OVx, 3) sham-L-Arg-A, 4) OVx-L-Arg-A, 5) sham-L-Arg-C, 6) OVx-L-Arg-C. The animals of sham-L-Arg-A and OVx-L-Arg-A were acutely treated with 500 mg/kg of L-Arg during 5 test days. Sham-L-Arg-C and OVx-L-Arg-C chronically received 500 mg/kg/day of L-Arg during 8 weeks before 5 test days. The animals in sham and OVx groups received 1 ml/kg saline instead of L-Arg. At the end of the experiment, the animals were tested in Morris water maze and the escape latency and traveled path to reach the platform were compared between groups. Results showed that the escape latency and traveled path in OVx group were significantly higher than in sham group ( p <0.05). The animals in OVx-L-Arg-A group had significantly lower traveled path length and escape latency compared to OVx group ( p <0.001). Chronic treatment by L-Arg had no significant effect on learning and memory in OVx and sham-operated animals. It seems that L-Arg has a role in Morris water maze tasks disturbances in OVx rats but it needs to be further investigated.