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Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

View Article: PubMed Central - PubMed

ABSTRACT

The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment.

No MeSH data available.


Related in: MedlinePlus

Hippocampus tissue expressions of ERK2 and NCAM proteins. Results for each group of rats (n=5 rats/group) are the percent of hippocampus cells positive for NCAM1 and ERK. Percentages are the % positive cells in 5 randomly selected microscopic fields (400x magnification). *P<0.01 vs. epileptic roup; #P<0.01 vs. control group. NCAM1, neural cell adhesion molecule 1; ERK2, extracellular signal-regulated kinase 2.
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f4-ol-0-0-4882: Hippocampus tissue expressions of ERK2 and NCAM proteins. Results for each group of rats (n=5 rats/group) are the percent of hippocampus cells positive for NCAM1 and ERK. Percentages are the % positive cells in 5 randomly selected microscopic fields (400x magnification). *P<0.01 vs. epileptic roup; #P<0.01 vs. control group. NCAM1, neural cell adhesion molecule 1; ERK2, extracellular signal-regulated kinase 2.

Mentions: Figure 4 shows the results of the immunohistochemical analysis of NCMA1 and ERK2 protein expression in hippocampal tissue. Similar to the mRNA results, saline-treated SE rats had a greater percentage of NCAM1-positive cells in the hippocampus compared to control rats (P=0.001). Among the groups of SE rats, the percentages of NCAM1-positive cells in the hippocampus were ordered high to low as follows: Donepezil, aniracetam, saline, oxcarbazepine and carbamazepine. Furthermore, as with the mRNA results, saline-treated SE rats had relatively fewer ERK2-positive cells in the hippocampus compared to control rats (P=0.003). Among the groups of SE rats, the percentages of ERK2-positive cells in the hippocampus were ordered high to low as follows: Donepezil, aniracetam, saline, oxcarbazepine and carbamazepine. Thus, the effects of pharmacological intervention on NCAM1 and ERK2 expression in the hippocampus of epileptic rats with cognitive dysfunction was confirmed at the mRNA and protein levels (Table III).


Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction
Hippocampus tissue expressions of ERK2 and NCAM proteins. Results for each group of rats (n=5 rats/group) are the percent of hippocampus cells positive for NCAM1 and ERK. Percentages are the % positive cells in 5 randomly selected microscopic fields (400x magnification). *P<0.01 vs. epileptic roup; #P<0.01 vs. control group. NCAM1, neural cell adhesion molecule 1; ERK2, extracellular signal-regulated kinase 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997984&req=5

f4-ol-0-0-4882: Hippocampus tissue expressions of ERK2 and NCAM proteins. Results for each group of rats (n=5 rats/group) are the percent of hippocampus cells positive for NCAM1 and ERK. Percentages are the % positive cells in 5 randomly selected microscopic fields (400x magnification). *P<0.01 vs. epileptic roup; #P<0.01 vs. control group. NCAM1, neural cell adhesion molecule 1; ERK2, extracellular signal-regulated kinase 2.
Mentions: Figure 4 shows the results of the immunohistochemical analysis of NCMA1 and ERK2 protein expression in hippocampal tissue. Similar to the mRNA results, saline-treated SE rats had a greater percentage of NCAM1-positive cells in the hippocampus compared to control rats (P=0.001). Among the groups of SE rats, the percentages of NCAM1-positive cells in the hippocampus were ordered high to low as follows: Donepezil, aniracetam, saline, oxcarbazepine and carbamazepine. Furthermore, as with the mRNA results, saline-treated SE rats had relatively fewer ERK2-positive cells in the hippocampus compared to control rats (P=0.003). Among the groups of SE rats, the percentages of ERK2-positive cells in the hippocampus were ordered high to low as follows: Donepezil, aniracetam, saline, oxcarbazepine and carbamazepine. Thus, the effects of pharmacological intervention on NCAM1 and ERK2 expression in the hippocampus of epileptic rats with cognitive dysfunction was confirmed at the mRNA and protein levels (Table III).

View Article: PubMed Central - PubMed

ABSTRACT

The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P&lt;0.01). Performance in SE rats was improved with donepezil treatment (P&lt;0.01), but declined with carbamazepine (P&lt;0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P&lt;0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P&lt;0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment.

No MeSH data available.


Related in: MedlinePlus