Naser Naghdi

Intra CA1 insulin microinjection improves memory consolidation and retrieval

Although the brain was considered as an insulin-insensitive organ, recent studies have shown that insulin receptors exist in the brain and insulin modulates some of the brain tasks. Insulin and its receptor are found in specific areas of CNS with a variety of region-specific functions different from its direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. The improving effect of insulin on spatial memory acquisition has been shown. In the present study, the effect of insulin microinjection into the CA1 region of rat hippocampus on spatial memory consolidation and retrieval has been investigated. Insulin in 12 MU (but not in 0.5 and 6 MU) improved both memory retrieval and consolidation.

Microinjection of ritanserin into the dorsal hippocampal CA1 and dentate gyrus decrease nociceptive behavior in adult male rat

Prenatal 5HT depletion causes a significant decrease in the level of nociceptive sensitivity during the second phase of the formalin test behavioral response. These experiments were designed to test whether blocking 5HT2A/2c receptors in the CA1 region of the hippocampus and dentate gyrus would decrease nociceptive behaviors induced by a peripheral noxious stimulus formalin as an animal model of unremitting human being. The 5HT2A/2c receptor antagonist ritanserin (2, 4 and 8 microg/0.5 microl) was injected into the CA1 area and dentate gyrus of behaving rats 5 min before subcutaneous injection of formalin irritant. Nociceptive behaviors in both phases of the formalin test were significantly decreased by ritanserin (4 and 8 microg/0.5 microl) and ritanserin had no effect at 2 microg/0.5 microl. These results support the hypothesis that the hippocampal formation may modify the processing of incoming nociceptive information and that 5HT2A/2c receptor-sensitive mechanisms in the hippocampus may play a role in nociception and/or the expression of related behaviors.

Involvement of nitric oxide in insulin induced memory improvement

Although brain was considered as an insulin-insensitive organ, recently it has appeared that insulin has some interesting effects on some brain regions like hippocampus. It has been known that intra-hippocampally administered insulin can improve learning and memory. Knowing that insulin can stimulate nitric oxide (NO) synthesis via eNOS activation and also that NO synthase (NOS) inhibitors can affect learning and memory, the aim of this study was to assess if NO is involved in insulin induced memory improvement. Wistar male rats were intra-CA1 cannulated and the effect of post-training and pre-probe trial intra-hippocampal administration of N-nitro-L-arginine methyl ester (L-NAME) (5, 10, 30 microg), insulin+L-NAME+/-L-arginine were assessed in a single-day testing version of Morris water maze (MWM) task. Our results show that, l-NAME can prevent insulin induced memory improvement. This drug had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous nitric oxide has a role in spatial learning and memory improvement caused by insulin.

Genotype and allele frequencies of N-acetyltransferase 2 and glutathione S-transferase in the Iranian population.

1. Xenobiotic‐metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide interindividual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical‐induced carcinogenesis. The aim of the present study was to determine the frequencies of important allelic variants in the N‐acetyltransferase 2 (NAT2) and glutathione S‐transferase (GST) genes in the Iranian population and compare them with frequencies in other ethnic populations. 2 Genotyping was performed in a total of 229 unrelated healthy subjects (119 men, 110 women) for NAT2 and 170 unrelated healthy subjects (89 men, 81 women) for GST from the general Tehran population. A combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was applied for typing of NAT2 polymorphisms. Detection of GSTM1 and GSTT1 null alleles was performed simultaneously using a multiplex PCR assay. 3 The frequencies of specific NAT2 alleles were 0.299, 0.314, 0.380, 0.007 and 0.000 for *4 (wild‐type), *5 (C481T, M1), *6 (G590A, M2), *7 (G857A, M3) and *14 (G191A, M4), respectively. The most prevalent genotypes were NAT2 *5/*6 (29.70%) and *4/*6 (21.40%). The GSTM1‐ and GSTT1‐null alleles were detected in 44.7 and 21.2% of subjects, respectively. 4 We found that Iranians resemble Indians with regard to allelic frequencies of the tested variants of NAT2. The predominance of slow (49.36%) and intermediate (41.47%) acetylation status compared with wild‐type rapid acetylation status (9.17%) in the study group suggests the significant prevalence of the slow acetylator (SA) phenotypes in the Iranian population. Our data confirmed that Iranians are similar to other Caucasian populations in the frequency of both GSTM1‐ and GSTT1‐null alleles.

In vivo sodium salicylate causes tolerance to acute morphine exposure and alters the ability of high frequency stimulation to induce long-term potentiation in hippocampus area CA1

Effects of morphine on synaptic transmission and plasticity in the hippocampus area CA1 following in vivo sodium salicylate and the potential molecular mechanism were investigated. Population spikes (PS) were recorded from stratum pylamidale of area CA1 following stimulation of Schaffer collaterals in slices taken from control and sodium salicylate injected rats. To induce long term potentiation (LTP), a 100Hz tetanic stimulation was used. Acute in vitro morphine increased baseline PS amplitude in control slices but not in slices taken from sodium salicylate treated rats. In vivo chronic salicylate did slightly decrease and/or destabilize LTP of CA1 synaptic transmission. We also found that mRNA of NR2A subunit of NMDA receptor was reduced in the hippocampus of sodium salicylate treated rats as compared to control ones. Following LTP induction, the mRNA of NR2A and PP1 (protein phosphatase 1) in slices taken from salicylate-treated rats were more than those of control ones. After long-term exposure to in vitro morphine, high frequency stimulation (HFS) decreased NR2A mRNA level significantly in sodium salicylate treated slices. It is concluded that in vivo sodium salicylate causes tolerance to excitatory effect of morphine and changes the ability of HFS to induce PS LTP in the hippocampus area CA1 in vitro. These changes in synaptic response may be due to alterations in NR2A and PP1 expression.

Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels

Aggregated amyloid beta (Aβ) peptides are believed to play a decisive role in the pathology of Alzheimer’s disease (AD). Previous evidence suggested that exercise contributes to the improvement of cognitive decline and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise on spatial memory via central and peripheral Aβ clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aβ1–42 injection in male Wistar rats. We found Aβ1–42-treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aβ1–42 (sAβ1–42), decreased mRNA and protein expression of neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein receptor-related protein-1 (LRP-1) in the hippocampus. Aβ1–42-treated animals also exhibited a higher level of sAβ1–42 and a lower level of soluble LRP-1 (sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein content in the liver. However, exercise training improved the spatial learning and memory deficits, reduced both plaque load and sAβ1–42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aβ1–42-treated animals. Aβ1–42-treated animals subjected to treadmill exercise also revealed decreased levels of sAβ1–42 and increased levels of sLRP-1 in plasma, as well as increased levels of LRP-1 mRNA and protein in the liver. In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aβ clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD. Future studies need to determine their relative contribution.

Intra CA1 insulin microinjection improves memory consolidation

Background Although the brain was considered as an insulin-insensive organ, a recent study has shown that insulin receptors exist in the brain and insulin modulates some of the brain tasks [1]. Insulin and its receptors are found in specific areas of CNS with a variety of region specific functions different from its direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin/ insulin receptor has been shown to be involved in brain cognitive functions [2]. The improving effect of insulin on spatial memory acquisition has been showed [3]. In present study, the effect of insulin microinjection into the CA1 region of rat hippocampus on spatial memory consolidation has been investigated.

221 THE MEASUREMENT OF SEROTONIN AND 5-HYDROXYINDOLEACETIC ACID IN THE CA1 REGION IN FORMALIN TEST

Background and Aims: Neuropathy is a serious and disabling complication that contributes to increased morbidity and mortality in diabetic patients. There is progressive distal to proximal axonal atrophy that ultimately leads to Wallerian degeneration. This study was performed to identify the effect of soy bean on diabetic neuropathy using morphometry. Methods: Male Sprague-Dawley rats were grouped into control, diabetic with red chow diet and diabetic with soy bean diet. The myelinated nerve fibers were counted and fiber size distributions were evaluated in each group at 4 and 8 weeks respectively. Results: Diabetic neuropathy did not develop in streptozotocin-induced diabetic Sprague-Dawley rats at four weeks. At 8 weeks, the myelinated nerve fiber in diabetic with red chow diet was smaller in number than control and diabetic with soy bean diet group. The number of myelinated nerve fiber was not different in control and diabetic with soy bean diet. Histogram of fiber size distribution was shifted to left in diabetic with red chow and soy bean diet groups compared to control. The level of HbA1c was lower in diabetic with soy bean diet than red chow diet. Conclusion: Soy bean could be effective in the protection of neuropathy induced by diabetes mellitus.