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Proteome Analysis of Rat Hippocampus Following Morphine-induced Amnesia and State-dependent Learning.

Jafarinejad-Farsangi S, Farazmand A, Rezayof A, Darbandi N - Iran J Pharm Res (2015)

Bottom Line: Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus.Post-training administration of morphine decreased step-through latency.The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

ABSTRACT
Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity.

No MeSH data available.


Related in: MedlinePlus

A representation of hippocampus proteome profile following morphine administration. Protein extracts are separated according to their molecular weight at the second dimension using 12% SDS-PAGE. Arrowheads show different expressed proteins.
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Figure 3: A representation of hippocampus proteome profile following morphine administration. Protein extracts are separated according to their molecular weight at the second dimension using 12% SDS-PAGE. Arrowheads show different expressed proteins.

Mentions: Morphine which is used for pre and post operative pain management also modulates hippocampal-related learning (7), predominantly through µ-opioid receptors in a time- and dose-dependent manner. Our previous studies had shown that morphine could induce state-dependent learning (StD) which is a dual action of the opiate on learning and memory processes (3). Using passive avoidance learning, our previous results also showed that pre- or post-training administration of morphine induced amnesia via inhibiting the acquisition or consolidation of memory while pre-test administration of the same doses of the drug improved amnesia through facilitating memory retrieval (6,7). Considering that morphine administration alters the proteome profile of the hippocampus, we hypothesized that differential expression of hippocampal proteins may be involved in morphine-induced amnesia and state-dependent learning. It should be considered that neuroproteomics have been widely used to evaluate brain signal complexity and also help diagnose neuronal disorders. For example, the detailed proteome database of hippocampus reported by Fountoulakisand colleagues (2005) may be useful to better understanding of memory formation, and disorders like dementias, recurrent major depression and Cushing’s disease (39). In addition, a few studies, which have focused on neuroadaptive mechanisms associated with morphine dependence, have reported several profound changes in rat brain proteome following chronic treatment (28,29). On the basis of the above findings, in the present study, 2DGE (Figure 3) was used to detect differentially expressed proteins in two groups of animals which showed the dual action of morphine on passive avoidance learning compared with a control group. Three gels per group were prepared and comparison of protein spot patterns of gels across all groups was made by calculating the coefficients of variation of normalized spot volumes. Differentially expressed spots were excised for identification of proteins by combined MALDI-TOF-MS/MS. Finally 18 proteins whose MASCOT scores were inside 95% confidence level were obtained. The detailed properties of the proteins are listed in Table 2. These proteins belong to different functional groups including cytoskeleton, neurotransmitter secretion, energy metabolism and oxidative damage protection.


Proteome Analysis of Rat Hippocampus Following Morphine-induced Amnesia and State-dependent Learning.

Jafarinejad-Farsangi S, Farazmand A, Rezayof A, Darbandi N - Iran J Pharm Res (2015)

A representation of hippocampus proteome profile following morphine administration. Protein extracts are separated according to their molecular weight at the second dimension using 12% SDS-PAGE. Arrowheads show different expressed proteins.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403077&req=5

Figure 3: A representation of hippocampus proteome profile following morphine administration. Protein extracts are separated according to their molecular weight at the second dimension using 12% SDS-PAGE. Arrowheads show different expressed proteins.
Mentions: Morphine which is used for pre and post operative pain management also modulates hippocampal-related learning (7), predominantly through µ-opioid receptors in a time- and dose-dependent manner. Our previous studies had shown that morphine could induce state-dependent learning (StD) which is a dual action of the opiate on learning and memory processes (3). Using passive avoidance learning, our previous results also showed that pre- or post-training administration of morphine induced amnesia via inhibiting the acquisition or consolidation of memory while pre-test administration of the same doses of the drug improved amnesia through facilitating memory retrieval (6,7). Considering that morphine administration alters the proteome profile of the hippocampus, we hypothesized that differential expression of hippocampal proteins may be involved in morphine-induced amnesia and state-dependent learning. It should be considered that neuroproteomics have been widely used to evaluate brain signal complexity and also help diagnose neuronal disorders. For example, the detailed proteome database of hippocampus reported by Fountoulakisand colleagues (2005) may be useful to better understanding of memory formation, and disorders like dementias, recurrent major depression and Cushing’s disease (39). In addition, a few studies, which have focused on neuroadaptive mechanisms associated with morphine dependence, have reported several profound changes in rat brain proteome following chronic treatment (28,29). On the basis of the above findings, in the present study, 2DGE (Figure 3) was used to detect differentially expressed proteins in two groups of animals which showed the dual action of morphine on passive avoidance learning compared with a control group. Three gels per group were prepared and comparison of protein spot patterns of gels across all groups was made by calculating the coefficients of variation of normalized spot volumes. Differentially expressed spots were excised for identification of proteins by combined MALDI-TOF-MS/MS. Finally 18 proteins whose MASCOT scores were inside 95% confidence level were obtained. The detailed properties of the proteins are listed in Table 2. These proteins belong to different functional groups including cytoskeleton, neurotransmitter secretion, energy metabolism and oxidative damage protection.

Bottom Line: Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus.Post-training administration of morphine decreased step-through latency.The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

ABSTRACT
Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity.

No MeSH data available.


Related in: MedlinePlus