The role of hippocampus in memory reactivation: an implication for a therapeutic target against opioid use disorder.

Purpose of the review: The abuse of opioids induces many terrible problems in human health and social stability. For opioid-dependent individuals, withdrawal memory can be reactivated by context, which is then associated with extremely unpleasant physical and emotional feelings during opioid withdrawal. The reactivation of withdrawal memory is considered one of the most important reasons for opioid relapse, and it also allows for memory modulation based on the reconsolidation phenomenon. However, studies exploring withdrawal memory modulation during the reconsolidation window are lacking. By summarizing the previous findings about the reactivation of negative emotional memories, we are going to suggest potential neural regions and systems for modulating opioid withdrawal memory. Recent findings: Here, we first present the role of memory reactivation in its modification, discuss how the hippocampus participates in memory reactivation, and discuss the importance of noradrenergic signaling in the hippocampus for memory reactivation. Then, we review the engagement of other limbic regions receiving noradrenergic signaling in memory reactivation. We suggest that noradrenergic signaling targeting hippocampus neurons might play a potential role in strengthening the disruptive effect of withdrawal memory extinction by facilitating the degree of memory reactivation. Summary: This review will contribute to a better understanding of the mechanisms underlying reactivation-dependent memory malleability and will provide new therapeutic avenues for treating opioid use disorders.

[The impact of microRNAs on the evolution of metazoan complexity].

MicroRNAs (miRNAs) are a novel class of ~22 nt non-coding small RNAs. As crucial post-transcriptional regulators, miRNAs are involved in comprehensive biological processes such as developmental timing, cell proliferation and differentiation, oncogenesis and viral defenses. In addition to the roles in ontogenic physiology, researches on the area of miRNA phylogenetic conservation and diversity suggested that miRNAs play important roles in animal evolution through driving phenotypic variations in development. It has been postulated that miRNAs have enormous impacts on phenotypic variation and developmental complexity. Here we reviewed recent advances in the studies on the roles of miRNA in animal evolution, from aspects of the rate of miRNA evolution, the spatio-temporal expression pattern, the variation of target sites, and miRNA gene dynamics. We gave evidence to support the hypothesis that innovations in miRNA-mediated regulations drive the increase of metazoan complexity.

[Time course of gene expression of gamma-glutamylcysteine synthetase subunit and Nrf2 in brain tissues of rats exposed by deltamethrin].

OBJECTIVE: To investigate the time course of mRNA expression of gamma- glutamylcysteine synthetase light (GCSl) and heavy subunit (GCSh), as well as protein expression of both GCSh and NF-E2 related factor 2 (Nrf2) in cerebral cortex and hippocampus in rats exposed at single dose of deltamethrin (DM). METHODS: Wistar male rats were exposed at single dose of DM (12.50 mg/kg bw) with i.p. At various time points of post-exposure, the rats were sacrificed at indicated time, then their cerebral cortex and hippocampus were isolated. The relative amount of mRNA expression of these genes was measured by the method of reverse transcription polymerase chain reaction (RT-PCR). The protein level was detected by the method of immunohistochemistry and image analysis system. RESULTS: (1) At 5 and 48h after DM exposure, GCSh mRNA relative levels in cerebral cortex in rats were significantly decreased to 83.9% and 86.0% of mRNA level of corresponding tissue of control group at Oh, respectively (P < 0.05). At 5, 24 and 48h after DM exposure, transcriptional factors Nrf2 mRNA relative levels were more higher than those of both control and 72 h group and increased to 146.4%, 145.2% and 147.9% of those of control group at Oh,respectively (P < 0.05). (2) At 5 and 48h after DM exposure, GCSh mRNA relative levels in hippocampus were significantly increased to 118.4% and 118.4% of those of control group at 0h, respectively (P < 0.05). At 5h after DM exposure, GCSl mRNA relative levels in hippocampus were more higher than those of control,24h and 48h group and increased to 121.4% of those of control group at Oh (P < 0.05). CONCLUSION: After single dose of DM exposure, there are up-regulation of mRNA expression of both GCSh and GCSl gene in rats hippocampus, down-regulation of mRNA expression of GCSh gene and up-regulation of mRNA expression of Nrf2. gene in rats cerebral cortex under the experimental condition.

[Effects of deltamethrin on gene expression of some antioxidase, gamma glutamylcysteine synthetase and NFE2 related factor 2 (Nrf2) in brain tissue].

OBJECTIVE: To study the effects of deltamethrin (DM) on the mRNA expression of copper-zinc dependent SOD (CuZn-SOD), glutathione reductase (GR) and gamma glutamylcysteine synthetase (gamma-GCS) light subunit (GCSl), as well as on expression of both mRNA and protein of gamma-GCS heavy subunit (GCSh) and NFE2 related factor 2 (Nrf2) in cerebral cortex and hippocampus of rats. METHODS: Eighteen Wistar male rats were randomizedly divided into three groups, six for each group. The low dosage and high dosage DM treated groups were administrated intraperitoneally with DM (the daily dosage was 3.125, 12.500 mg/kg BWT respectively) for five consecutive days while the control group was administered intraperitoneally with olive oil. The relative amount of mRNA expression of these genes was measured by the method of reverse transcription polymerase chain reaction (RT-PCR) (n = 6). The protein level was detected by the method of immunohistochemistry and image analysis system (n = 4). RESULTS: There was no change in mRNA expression level of CuZn-SOD, GR, GCSh and Nrf2 gene in both cerebral cortex and hippocampus tissue in rats administrated with DM. However, the mRNA level of GCSl gene in cerebral cortex of high dosage group as well as in both cerebral cortex and hippocampus of the low dosage group was significantly lower than that in corresponding tissue in the control group, and was decreased to 71.1%, 63.6% and 75.2% of mRNA level of corresponding tissue in the control group (P < 0.01). There was no obvious effect on protein level of both GCSh and Nrf2 in CA1, CA2, CA3 and dentate gyrus (DG) of hippocampus as well as on that in cerebral cortex in rats treated with DM. CONCLUSION: Under the experimental conditions, there is no obvious effect in the mRNA expression level of CuZn-SOD, GR gene, as well as on expression of both mRNA and protein of Nrf2 gene in both cerebral cortex and hippocampus tissue in rats administered with DM. DM depresses the mRNA expression of GCSl gene, but does not affect the mRNA expression of GCSh gene.

[Oxidative stress of deltamethrin on rat nervous system].

OBJECTIVE: To explore the lipid peroxidation induced by deltamethrin (DM) in the cerebral cortex and hippocampus of rat. METHODS: Wistar male rats were administrated with DM (daily dose was 3.125, 12.500 mg/kg respectively). The content of malondialdehyde (MDA) and the activity of total-superoxide dismutase (T-SOD, including Mn-SOD and CuZn-SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in cerebral cortex and hippocampus tissue were determined. The reduced glutathione (GSH) content and gamma-glutamylcysteine synthetase (gamma-GCS) activity in cytosolic fraction of cerebral cortex and hippocampus tissue was determined by reversed-phase high performance liquid chromatographic assay with o-phthalaldehyde pre-column derivation. RESULTS: (1) MDA content in cerebral cortex of the high dose group was significantly higher than those in the low dose group, and MDA content in hippocampus tissue of the high dose group was significantly higher than those in both the control and the low dose group after 5 d of DM exposure. (2) The activity of T-SOD and CuZn-SOD in cerebral cortex of both high and low dose group were significantly lower than that in the control group, and there was no effect on CAT activity in cerebral cortex (P < 0.01 or P < 0.05). (3) GSH content in cerebral cortex of the high dose group was significantly higher than that in control group (P < 0.05), and that in hippocampus tissue of high dose was significantly lower than that in both control and low dose group (P < 0.05). GR activity of low dose group in cerebral cortex was significantly lower than that in both control and high group [(11.80 +/- 5.15) vs (18.98 +/- 3.68), (17.35 +/- 2.47) U/mg pro] (P < 0.01). Gamma-GCS activity in hippocampus tissue of the high dose group was significantly lower than that in both control and low dose group [(1.75 +/- 0.60) vs (3.17 +/- 0.79), (2.72 +/- 0.75) nmol x mg pro(-1) x min(-1)] (P < 0.01). GR activity in hippocampus tissue of both high and low dose group was significantly lower than that in the control group [(21.63 +/- 4.92), (21.46 +/- 8.89) vs (31.22 +/- 6.97) U/mg pro] (P < 0.05). CONCLUSION: The oxidative stress in nerve tissue, which could be resulted from effect of DM on the activity of SOD, gamma-GCS and GR and GSH content, is one of the mechanisms of neuro-toxicity induced by DM; The decreased activity of gamma-GCS and GR may be the primary cause of DM-induced decrease in that GSH content in hippocampus tissue.

[Effects of deltamethrin on the apoptosis and the expression of caspase-3 in rat neural cells].

OBJECTIVE: To study the effect of deltamethrin on the apoptotic rate and the expression of caspase-3 in rat neural cells. METHODS: Male Wistar rats were randomly divided into 5 groups: control, 5 h, 24 h, 48 h and 5 d exposed groups. Apoptotic rate and the expression of caspase-3 were measured by FACS420 Flow Cytometer; Ac-DEVD-pNa was used as a substrate to detect the activity of caspase-3. RESULTS: Apoptotic rates in 24 h, 48 h and 5 d exposed groups in hippocampus and cerebral cortex [hippocampus: (8.45 +/- 1.02)%, (9.44 +/- 1.14)%, (7.58 +/- 0.75)%; cerebral cortex: (7.90 +/- 0.49)%, (8.01 +/- 0.87)%, (7.97 +/- 0.41)% respectively] were higher than those in the control [hippocampus: (2.97 +/- 0.36)%; cerebral cortex: (3.50 +/- 0.48)%] (P < 0.01); the activity of caspase-3 in 5 h, 24 h and 48 h exposed groups (A(405) nm in hippocampus: 0.389 +/- 0.038, 0.472 +/- 0.041, 0.295 +/- 0.049; A(405) nm in cerebral cortex: 0.321 +/- 0.068, 0.429 +/- 0.077, 0.344 +/- 0.047) and 5 d group of hippocampus (0.246 +/- 0.065) were all higher than those of the control (hippocampus: 0.184 +/- 0.054; cerebral cortex: 0.198 +/- 0.049) (P < 0.05, P < 0.01); the expression of caspase-3 in 5 h, 24 h and 48 h exposed groups increased apparently while 5 d group did not. CONCLUSION: Exposure to high dose of deltamethrin would affect the apoptosis, the activity and expression of caspase-3 in rat neural cells. The increase in caspase-3 activity and expression occurred before the rising of neuronal apoptotic rate may be the upstream event of apoptosis.