Avoidance and escape conditioning adjust adult neurogenesis to conserve a fit hippocampus in adult male rodents

In this study, the connection between cognitive behaviors and the adult rodent hippocampus was investigated. Recording field potentials at performant pathway (PP)–hippocampal dentate gyrus (DG) synapses in transverse slices from the dorsal (d), intermediate (i), and ventral (v) hippocampus showed differences in paired-pulse responses and long-term potentiation in rats. The Barnes maze (BM) and passive avoidance (PA) tests indicated a decrease in escape latency and step-through latency in both rats and mice over training days. A decrease in the use of random or sequential strategy while an increase in the use of direct strategy to search for an escape box occurred in both groups. Evaluation of the levels of neurogenesis markers (Ki67 and BrdU/NeuN) by immunofluorescence assay in the dDG, iDG, and vDG revealed a long-axis disparity in the hippocampal dentate baseline cell proliferation and exposure to the BM and PA task changed the profile of baseline cell proliferation along the DG in both rats and mice. Also, these learning experiences changed the profile of BrdU⁺/NeuN⁺ cells along the DG of rats. Quantitation of hippocampal BDNF protein levels using ELISA exhibited no changes in BDNF levels due to learning experiences in rats. We demonstrate that PP–DG synaptic efficacy and neurogenesis are organized along a gradient. Avoidance and escape conditioning themselves are sufficient to change and calibrate adult neurogenesis along the hippocampal long axis in rodents. Further research will be required to determine the precise mechanisms underlying the role of experience-derived neuroplasticity in cognitive function and decline.     

A new series of Schiff base derivatives bearing 1,2,3‐triazole: Design,synthesis, molecular docking,and α‐glucosidase inhibition

A series of new Schiff bases bearing 1,2,3‐triazole 12a ? o was designed, synthesized, and evaluated as α‐glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α‐glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α‐glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α‐glucosidase.     

Contribution of ionotropic glutamate receptors and voltage-dependent calcium channels to the potentiation phenomenon induced by transient pentylenetetrazol in the CA1 region of rat hippocampal slices

The role of ionotropic glutamate receptors and voltage-dependent calcium channels (VDCCs) in potentiation phenomenon and epileptic activity induced by a transient pentylenetetrazol (PTZ) application in the CA1 region of rat hippocampal slices was investigated. Also we examined whether adenosine as an inhibitory neuromodulator would interact with expression of the long-lasting effect of transient PTZ. Population spikes (PS) were recorded in the CA1 cell body layer of the hippocampal slices following stratum radiatum stimulation. Changes in the PS amplitude potentiation and number of extra PS, which induced by transient PTZ were used as indices to quantify the effects of drugs. PS input-output curve was significantly increased 10 min after PTZ application and persisted at least for 60 min after PTZ washout. Polyspikes also appeared, but did not persist. Both ketamine and APV reduced the extent of potentiation of PS amplitude but had no effect on number of extra PS. The selective non-NMDA receptor antagonist CNQX prevented the amplitude potentiation and the generation of extra PS. The blocker of VDCCs, verapamil, prevented the amplitude potentiation and inhibited polyspike activity. Co-application of adenosine and PTZ produced a rapid and reversible decrease in the PS amplitude, but PTZ-induced potentiation phenomenon was observed after washout. It is concluded that ionotropic glutamate receptors as well as VDCCs involve in the PTZ-induced LTP of PS amplitude. PTZ-induced LTP is also insensitive to adenosine. The epileptiform activity induced by a transient PTZ application could be attributed to VDCCs. The polyspikes mediated by VDCCs are dependent on prior activation of AMPA receptors.     

Effect of transient hippocampal inhibition on amygdaloid kindled seizures and amygdaloid kindling rate

In this study the effect of transient inhibition of the CA1 region of the dorsal hippocampus by lidocaine on amygdala kindling rate and amygdaloid kindled seizures was investigated. In experiment 1, rats were divided into four groups. In group 1, animals were implanted only with a tripolar electrode into the amygdala but in groups 2-4, two guide cannulae were also implanted into the CA1 regions of the dorsal hippocampi. Animals were stimulated daily to be kindled. In groups 3 and 4, saline or 2% lidocaine (1 microl/2 min) was also injected respectively into the hippocampus, 5 min before each stimulation. Results obtained showed that amygdala kindling rate and the number of stimulations to receive from stage 4 to stage 5 seizure were significantly increased in group 4. In experiment 2, lidocaine (1% and 2%) was infused (1 microl/2 min) into the hippocampus of amygdala kindled rats bilaterally and animals were stimulated at 5, 15 and 30 min after drug injection. Twenty four h before lidocaine injection, saline was also infused (1 microl/2 min) into the hippocampus as control. Obtained results showed that afterdischarge duration was reduced 5 min after lidocaine (1% and 2%) injection. Stage 5 seizure duration was also decreased 5 and 15 min after 2% lidocaine. Thus, it may be suggested that in amygdala kindling, activation of the hippocampal CA1 region has a role in seizure acquisition and seizure severity so that inhibition of this region results in decreasing of seizure severity and retards amygdala kindling rate.     

Reversal of pentylenetetrazol-induced potentiation phenomenon by theta pulse stimulation in the CA1 region of rat hippocampal slices

The effect of theta pulse stimulation (TPS) on pentylenetetrazol (PTZ)-induced long-term potentiation of population spikes was studied in the CA1 region of rat hippocampal slices. The field excitatory postsynaptic potential (fEPSP) and population spikes (PS) were recorded from strata radiatum and pyramidale, respectively, following stimulation of Schaffer collaterals. A transient PTZ application produced a long-lasting enhancement of PS amplitude. A 3-min episode of TPS delivered at test-pulse intensity failed to reverse the PTZ potentiation. However, the same stimulation at a higher intensity produced complete reversal of the PTZ potentiation when delivered during the last minutes of PTZ application. Prior application of high-intensity TPS also decreased the amount of PTZ potentiation, whereas it had no long-lasting effect on baseline synaptic responses. High-intensity TPS induced reversal was blocked by adenosine A1 receptor antagonist and, furthermore, was reduced by protein phosphatase 1 inhibitor. The results suggest that mechanism of PTZ-induced LTP reversal involves activation of adenosine receptors and protein phosphatases.     

The effect of peripheral administration of growth hormone on AD-like cognitive deficiency in NBM-lesioned rats

Over-expression of blood–brain barrier P-glycoprotein is considered as a major hurdle in the treatment of various CNS disorders. A down-regulation strategy is considered as one means to counteract disease- or therapy-associated induction of P-glycoprotein. Here, we evaluated whether a targeting of P-glycoprotein can be achieved in mouse brain capillary endothelial cells using siRNA. A 4-day treatment paradigm with once daily hydrodynamic intravenous injections of siRNA resulted in a significant reduction of the P-glycoprotein-labeled area in the hippocampal hilus and parietal cortex. P-glycoprotein expression proved to be down-regulated in these brain regions by 31 and 16%, respectively. An impact of siRNA administration on density of brain capillaries was excluded by quantification of the endothelial cell marker GLUT-1. In conclusion, the study provides first preliminary evidence that a down-regulation of P-glycoprotein can be achieved in brain capillary endothelial cells by administration of siRNA in vivo.     

Anticonvulsant effects of N6-cyclohexyladenosine microinjected into the CA1 region of the hippocampus on entorhinal cortex-kindled seizures in rats.

In this study, the role of adenosine A1 receptors of the hippocampal CA1 region in entorhinal cortex-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of the entorhinal cortex. In fully kindled rats, N(6)-cyclohexyladenosine (CHA; a selective A1 receptor agonist) and 1, 3-dimethyl-8-cyclopenthylxanthine (CPT; a selective A1 receptor antagonist) were microinfused bilaterally into the hippocampal CA1 region. Rats were stimulated and seizure parameters were measured. Results obtained showed that CHA (10 and 50 micro moles) decreased the afterdischarge duration (ADD) in the hippocampal CA1 region and entorhinal cortex, stage 5 seizure duration (S5D) and seizure duration (SD) only at the dose of 50 micro moles, and significantly increased the latency to stage 4 (S4L). Intrahippocampal CPT increased ADD and S5D, and significantly reduced the latency to stage 4 (S4L) at the dose of 10 micromoles. Pretreatment of rats with CPT (5 micro moles) before CHA (50 micro moles), significantly reduced the effect of CHA on seizure parameters. The results suggest that the CA1 region of the hippocampus plays an important role in spreading seizure spikes from the entorhinal cortex to other brain regions and activation of adenosine A1 receptors in this region participates in the anticonvulsant effects of adenosine agonists.     

Protective effects of Swertia longifolia Boiss. and its active compound, swerchirin, on paracetamol-induced hepatotoxicity in mice

Aerial parts of Swertia longifolia Boiss. (Gentianaceae), which grows in the north of Iran, were screened for hepatoprotective activity against paracetamol (acetaminophen)-induced hepatotoxicity in Swiss mice. Pretreatment with total plant extract and swerchirin, the major component of the plant, significantly reduced the elevation of biochemical parameters, AST (aspartate aminotransferase), ALT (alanine aminotransferase) and ALP (alkaline phosphatase), the enzymes that are increased by liver damage (P < 0.001). Our results indicated that total plant extract and swerchirin were hepatoprotective in the range of 6-50 mg kg(-1) orally.