Sodium Nitroprusside Does Not Prevent an Inhibitory Effect of Carnosine on Long-Term Potentiation in the Dentate Gyrus of Rats

Carnosine is co-localized in glutamergic terminals and may be released together with glutamate. Carnosine is a selective inhibitor of NO-dependent activation of guanylate cyclase (GC). Nitric oxide (NO) is known to affect the synaptic plasticity in the brain via the cGMP-dependent protein kinase pathway. Nitric oxide can be released from its donor sodium nitroprusside (SNP), and GC activity might be stimulated by SNP in a concentration-dependent manner. In our previous study, we found that microinfusions of 10 mg carnosine decreased long-term potentiation (LTP) in the rat dentate gyrus in vivo; it was supposed that carnosine decreased LTP via inhibition of soluble GC. We aimed at examination of interaction between SNP and carnosine in the course of hippocampal-dependent learning in rats. Effects of infusions of artificial cerebrospinal fluid (aCSF), 0.9 mu g SNP, 10 mu g carnosine, and 10 mu g carnosine + 0.9 mu g SNP into the dentate gyrus of rats were compared. The medial perforant path was subjected to high-frequency stimulation (HFS, 100 sec(-1), 1 sec). While the SNP-infused group of animals demonstrated higher population spike (PS) amplitudes than the carnosine and carnosine + SNP groups, there was no significant difference between the SNP and aCSF (control) groups. Thus, SNP induced more intense LTP, while carnosine reduced this process. When these drugs were administered in combination, PS amplitudes reduced with carnosine were partly increased with SNP. This increment was insignificant at the SNP dose used. Therefore, SNP did not prevent an inhibitory effect of carnosine on LTP. We consider that the inhibitory effect of carnosine in relatively low doses cannot be explained by its inhibitory influence on soluble GC

Low-frequency stimulation induces a durable long-term depression in young adult hyperthyroid rats: the role of p38 mitogen-activated protein kinase and protein phosphatase 1

Long-term potentiation and long-term depression (LTD) are cellular mechanisms of learning and memory in the mammalian brain. We have previously shown that adult hyperthyroid rats showed a delay in the acquisition of a place learning task and attenuated long-term potentiation. However, changes in LTD in hyperthyroidism remain unclear. Rats were administered 0.2 mg/kg/day of L-thyroxine for 21 days starting at postnatal day 40 to induce hyperthyroidism. LTD was induced in the dentate gyrus using low-frequency stimulation (LFS) of the perforant pathway. The mRNA expressions of p38 mitogen-activated protein kinase (p38-MAPK) and protein phosphatase 1 (PP1) were evaluated using a quantitative reverse transcriptase PCR. In control rats, a standard LFS protocol induced a slight depression of the population spike (PS) amplitude during the induction phase of LTD (76 +/- 13% vs. baseline), but a small potentiation of the PS amplitude was observed in the early (107 +/- 18%) and late (111 +/- 20%) phases of LTD. Interestingly, in the hyperthyroid rats, the same LFS protocol induced a reliable LTD in the dentate gyrus of the hippocampus as evidenced by a marked depression in the PS amplitude during the induction (54 +/- 6% vs. baseline) and the early phases (56 +/- 8%) of LTD. Elevated mRNA levels of p38-MAPK and PP1 were observed in the hippocampus of the LFS-treated hyperthyroid rats compared with the hippocampus of the vehicle-treated hyperthyroid rats. No significant change in p38-MAPK or PP1 mRNA expression was observed in the euthyroid rats. The present study shows that a standard LFS protocol can induce a durable depression of synaptic strength and an upregulation of PP1 and p38-MAPK mRNA in hyperthyroid rats. We conclude that hyperthyroidism can induce molecular changes associated with degeneration of the hippocampus. The relationship between the levels of thyroid hormone and dementia requires further investigation. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved

Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways

Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wildtype counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved

Intraperitoneal Administration of Low Dose Aluminium in The Rat: How Good is It to Produce a Model for Alzheimer Disease

Since neurooxicity of aluminium (Al) resembles the progressive neurodegeneration observed in Alzheimer Disease (AD), Al administration in several ways has been used to produce AD model. Intraperitoneal (ip) low dose (4.2 mg/kg) Al injection in rats for long periods is the preferred method by some researchers. In this paper, the efficiency of this method for producing an AD model was evaluated