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1

Association of the CHRNA4 1674plus11C>T polymorphism with juvenile myoclonic epilepsy

100%
Rozycka A., Steinborn B., Dorszewska J., Trzeciak W. H.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
The α-4 subunit gene (CHRNA4) of the neuronal nicotinic acetylcholine receptor (nAChR), linked to an idiopathic partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), may also play a key role in the development of the idiopathic generalized epilepsy syndrome (IGE), juvenile myoclonic epilepsy (JME). This study was designed to explore an association of four polymorphisms of the CHRNA4 with JME in Polish children and young patients. The study included 92 JME patients and 222 unrelated healthy individuals. In each group the frequencies of the CHRNA4 c.555C>T, c.594C>T, 1674+11C>T, and 1674+14A>G polymorphisms were determined using PCR-RFLP analyses. An association between the 1674+11C>T polymorphism of the CHRNA4 and JME was evidenced. Allele T (the risk factor) appeared with a significantly higher frequency in the JME patients than in the controls (p=0.0299). The patients harboring the 1674+11CT+TT genotypes showed an increased risk of JME (CT+TT versus CC: OR=1.925; 95% CI=1.021-3.629; p=0.0408). No association was found for the other CHRNA4 polymorphisms tested. The CHRNA4 1674+11C>T polymorphism may be a susceptibility factor for epilepsy, and its higher frequency in patients with juvenile myoclonic epilepsy suggests that the CHRNA4 may be one of the candidate genes for this epileptic syndrome.
2

Extent of the oxidative damage to DNA (8-oxo-2dG) in multiple sclerosis

100%
Dorszewska J., Michalowska-Wender G., Wender M.
Acta Neurobiologiae Experimentalis
|
2009
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tom 69
|
nr 1
There are some hypotheses that oxidative damage to DNA secondary to infl ammation may contribute to irreversible alterations in MS plaques. To test this assumption, we have estimated the level of a DNA oxidative marker, the level of a purine oxidation product, the 8-oxo-2-deoxyguanosine (8-oxo-2dG) in lymphocytes of MS patients. Material and methods: Peripheral blood was collected from 28 patients with clinically defi nite MS aged from 19 to 46 years. The duration of MS was 4.2 ± 3.1 years. The mean of EDSS was 2.0 ± 0.8. In MRI study 14 cases were gadolinium positive and 14 negative. Thirty healthy volunteers make up the control group. DNA was isolated from peripheral blood lymphocytes and then hydrolyzed to nucleosides using P1 nuclease. In order to determine 8-oxo-2dG level, the nucleoside mixture was applied to the HPLC/ UV system, coupled to an electrochemical detector. Results and discussion: The mean level of 8-oxo 2dG in MS patients was 19.6 ± 35.1 and, compared to that established for control subjects (12.3 ± 7.2), showed no statistically signifi cant differences. The comparison of 8-oxo-2dG in subgroups of patients divided according to duration of the disease showed the higher number of cases with DNA damage in patients of the subgroup with shorter duration of the disease. The mean level of 8-oxo-2dG in gadolinium positive MS cases was 17.3 ± 13.1 and in gadolinium negative ones it was 9.6 ± 4.0. The difference was signifi cant. Conclusions: (1) Oxidative damage to DNA is not a general feature in MS patients but it may frequently appear in the early period of the disease; (2) The higher level of oxidative marker of DNA damage in MS, noted in active period of the disease, testifi es to the relationship between the studied variable and MS process.
3

Analysis of mutation in SPR and HTRA2 genes in patients with Parkinson’s disease

88%
Polrolniczak A., Dorszewska J., Florczak-Wyspianska J., Owecki M., Kozubski W.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
Diagnosis of Parkinson’s disease (PD) is often problematic because clinically it can be difficult to distinguish idiopathic PD from the other extrapyramidal disorders. It is known, that PD is caused either by environmental and genetic factors . Genetic mutations are the cause of familial form of PD and include genes PARK1-PARK18. The etiology of sporadic PD (SPD) is still not clear, but it is currently assumed that genetic susceptibilities, may be involved. It is suggested, that in pathogenesis of the SPD beside SNCA and PARK2 genes, may be involved also SPR (sepiapterin reductase gene) [PARK3] and HTRA2 (HTRA serine peptidase 2 gene)[PARK13] genes. The HTRA2 gene, also known as Omi, was found to be associated with PD in German population. However, some studies have indicated that some variants of HTRA2 may not be related to PD. SPR gene, which is located in the PARK3 linkage region is inconsistently associated with a risk of PD but significance of mutations in this gene as well as HTRA2 in PD is still not clear. The aim of the study was the analysis of the frequency of T637A/G SPR as well G421T, G1195A and C1210T mutations in HTRA2 gene in Polish patients with PD and in control group. Peripheral blood was collected from 89 patients with PD clinical diagnosis (42F and 47M, the avr. age 62 ± 10.15 years), and from 113 healthy donors (79F and 7M, the avr. age 55.5 ± 9.54 years). Genomic DNA was isolated using standard protocols. Genotyping was performed by PCR/RFLP using specific primers and restriction enzymes (SsiI, MboII, MvaI, MspI) and sequencing. The SPR gene analysis detected T637A mutation in 3 (3%) PD patients compared to 2 (2%) persons in the control group. Moreover, mutations G421T and G1195A of HTRA2 gene have been identified in 3 (3%) [G421T – 1%, G1195A – 2%] patients with PD and none of controls. Analysis of C1210T HTRA2 mutation detected no mutated variant both in PD patients group and in control group. It was also observed that the stage of the disease was 1–2 in Hoehn and Yahr scale and response to L-dopa was good in patients with T637A SPR and G421T, G1195A HTRA2 mutations. It was also observed some tendency for depression manifestation in PD patients with T637A SPR mutation. It can be concluded, that mutations of SPR and HTRA2 genes probably may be one of the risk factor for manifestation of PD. Thus, the results of this study suggest that analysis of T637A SPR and G421T, G1195A HTRA2 genes mutations may be an additional diagnostic and prognostic factor in PD patients in the future.
4

The APOE genotype and the plasma expression of microRNA-107, -132 and -138 in patients with Alzheimer's disease-preliminary study

76%
Prendecki M., Florczak-Wyspianska J., Lagan-Jedrzejczyk U., Plociennik A., Kozubski W., Dorszewska J.
Acta Neurobiologiae Experimentalis
|
2015
|
tom 75
|
nr Supl.
BACKGROUND AND AIMS: Alzheimer’s disease (AD) is a multifactorial disease conditioned by genes (70%) and environment (30%), characterized by brain deposition of amyloid-β and neurofibrillary tangles. An involvement of over 20 genes (including APOE) and dozens of microRNAs (e.g. miR-107) has been previously described in the pathogenesis of AD. APOE has 3 common variants: protective – ε2, neutral – ε3 and pathogenic – ε4. The miR-107, associated with amyloid cascade, seems to be a promising AD plasma biomarker, whose downregulation has been demonstrated in the early stage of the disease. Though miR-132 has been linked with apoptosis of neurons and miR-138 with tau hyperphosphorylation, their role in AD remain unclear, and neither of these miRNA has been previously associated with APOE. The aim of the study was the analysis of APOE genotypes and the expression of three miRNAs: miR-107, -132, -138 in patients with AD and in control subjects, both related and unrelated to AD cases. METHODS: The DNA from 100 subjects (aged 47–83), including 42 patients with AD and 15 related and 43 unrelated controls of the same age was genotyped by “mismatch primer” qPCR. The subsequent expression analysis of miR-107, -132 and -138 in the plasma of ten subjects was performed by qPCR. RESULTS: Our study have shown that the miR-107 was significantly downregulated in AD patients (P<0.05) comparing to related controls, but did not reach significance as compared to unrelated controls. The downregulation of miR-132 was not statistically significant as compared to related and unrelated subjects. Expression of miR-138 in AD was decreased only as compared to relatives. Subsequently, the presence of two APOE ε4 alleles in AD patient and at least one ε4 copy in the controls was associated with altered expression of the analyzed miRNAs. CONCLUSIONS: It appears that in the course of AD the expression of miR-107, -132 and -138 depends on the APOE genotype.
5

Homocysteine, cysteine and gluthatione in epileptic patients treated with antiepileptic drugs

76%
Bugaj R., Urbanska N., Dorszewska J., Sniezawska A., Przedpelska-Ober E., Kozubski W.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
Today, epilepsy is regarded as the most common neurological disease. AEDs pharmacotherapy, used to treat patients with epilepsy affect plasma concentrations of sulfur amino acids: Hcy, Cys and GSH. These are the main intracellular thiols, whose anabolic and catabolic pathways are closely linked. Through transsulfuration of Hcy arises Cys, who further participates in the synthesis of GSH. It has been shown that the increase of plasmatic Hcy in patients with epilepsy taking AEDs can be affected by a number of factors including diet, type of pharmaceutical preparations taken, the duration of treatment, and genetic factors. The study group consisted of 63 patients with idiopathic epilepsy, 28 women and 35 men, aged from 18 to 65. Among patients with epilepsy 55 people, 24 women and 31 men, aged from 18 to 65 were treated with various AEDs, and 8 patients, 4 women and 4 men, aged between 18 and 65 were before the inclusion the anticonvulsant therapy. A preliminary analysis in our studies was conducted on 38 people from the control group, 28 women and 10 men, aged from 22 to 67, without symptoms of dementia or any other neurological disorders. The concentration to sulfur amino acids (Hcy, Cys, GSH) in plasma has been identified by HPLC (high performance liquid chromatography) with electrochemical detection. The analysis was performed in Thermo Hypersil BDS C18 column (250x4, 6x5 µm) using phosphate buffer with 12.7% acetonitrile as mobile phase for the determination of Hcy and GSH, and phosphate buffer with 10% acetonitrile as buffer mobile phase for the determination of Cys. Studies show that AEDs pharmacotherapy in patients with epilepsy leads to a significant increase in Hcy- treated in polytherapy, especially in the application of VPA and the long-term treatment. In addition, in patients with epilepsy treated with VPA in monotherapy, plasma Cys concentration is significantly reduced. Moreover, it was observed that long-term AEDs treatment and mild HHcy (Hcy>16 µmol/l) in patients with epilepsy leads to a significant increase in GSH concentration. It can be assumed that patients with epilepsy using AEDs are exposed to high oxidative stress, which is an index for the observed higher concentrations of GSH, the main intracellular antioxidant. It also seems that only the combined supplementation of vitamins B and FA in patients with epilepsy treated with AEDs may contribute to the effective regulation of Hcy- the risk factor for vascular diseases.
6

Polymorphisms of the PARK2 gene and Parkin protein levels in patients with Parkinson’s disease

76%
Dorszewska J., Debek A., Oczkowska A., Florczak-Wyspianska J., Owecki M., Kozubski W.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
Parkinson’s disease (PD) is one of the most common degenerative diseases of the extrapyramidal system, the frequency of which increases with age. It is now believed that the causes of PD are environmental and genetic factors. Important genetic factors resulting in PD are mutations in the PARK2 gene, which may affect the level of Parkin. The aim of the study was conducted on 234 individuals of the Polish population: 89 patients diagnosed with PD, 32 patients diagnosed with Parkinson’s syndrome and 113 individuals from the control group without neurological symptoms and characteristics of dementia. As a result of the methods of analysis demonstrated the following: G930C mutation of exon 8 in the PARK2 gene, which was analysed by performing PCR-RFLP. Detection of deletion of exon 2 using PCR. Whereas the evaluation of mutations within exon 11 in PARK2 gene was performed using HRM method and sequencing. Also performed to measure the concentration of Parkin’s plasma in blood using ELISA method. The study results no presence of the deletion of exon 2 in the PARK2 gene in any individual study. At the same time, it was almost 3-times higher frequency of G930C mutation in exon 8 PARK2 in patients with PD and almost 6-times higher incidence of mutation G1281 A in exon 11 of PARK2 in PD patients compared with controls. At the same time, in the present study demonstrated that the presence of mutations in 8 and 11 exon of PARK2 gene does not appear to be associated with the generate of Parkin’s plasma concentration. Genotype-fenotype study in the PARK2 gene can constitute intravital diagnostic tests in patients with PD, as well as in patients diagnosed with Parkinson’s syndrome in the course of a degenerative disease.
7

Carotid intima-media thickness better differentiates between groups of stroke patients and persons without cerebrovascular disease than other conventional and novel risk factors

76%
Kazmierski R., Watala C., Podsiadly E., Dorszewska J., Adamczewska-Goncerzewicz Z., Tylewska-Wierzbanowska S., Kozubski W.
Folia Morphologica
|
2004
|
tom 63
|
nr 3
When measured by ultrasound, the morphological markers of carotid atherosclerosis such as intima-media thickness (IMT) and cross-sectional plaque area have been associated with the risk of ischaemic stroke. We set out to determine whether the morphological parameters of the carotid arteries made it possible to better differentiate between groups of older atherothrombotic stroke patients and persons without cerebrovascular disease than conventional and novel risk factors of stroke. Of the total number of 623 persons examined, 54 stroke patients (mean age 63.3 years) and 74 controls without cerebrovascular disease (mean age 66.3 years) fulfilled the inclusion criteria for this investigation and were enrolled in the case-control study. After adjustment for age, gender and education level, the strongest associations were found between stroke and carotid IMT [odds ratio (OR) = 10.6; 95% confidence interval (CI): 4.3–26.9] and plaque area (OR = 5.4; 95%CI: 2.3–13.1). Other risk factors showed weaker associations with stroke occurrence. Of the clinical risk factors, a significant association was found between stroke and coronary heart disease (OR = 3.5; 95%CI: 1.2–10.2), hypertension (OR = 3.2; 95%CI: 1.5–7.2) and smoking (OR = 2.7; 95%CI: 1.1– –6.4). From the laboratory-derived risk factors a significant association was found between stroke and triglyceride levels (OR = 4.4; 95%CI: 1.9–10.0), and an inverse correlation was observed between stroke occurrence and HDL-cholesterol level (OR = 0.4; 95%CI: 0.2–0.8). The carotid IMT and plaque area, measured with the use of ultrasonography, showed a better correlation with stroke occurrence than currently recognised clinical and biochemical risk factors. The intima-media thickness and plaque area of the carotid arteries could be useful parameters in the development of strategies to identify patients at high risk of atherothrombotic ischaemic stroke.
8

Analiza zmian w układzie immunologicznym podczas procesu starzenia się i onkogenezy psów

64%
Kempisty B., Zawierucha P., Zaorska K., Dorszewska J., Bukowska D., Jaskowski J. M., Nowicki M., Zabel M.
Medycyna Weterynaryjna
|
2011
|
tom 67
|
nr 09
Senescence of the organism is a consequence of several molecular (induction of proapoptotic genes expression, DNA damage) and biochemical changes, which gradually leads to the degeneration of some systems and organs. One of the most important features of progressive senescence is also a decreased response of the immunological system (proinflammatory response), which may result in a higher susceptibility to infection. The process of oncogenesis is closely associated with the age of an animal and progressive senescence. However, the proper assessment of the association between the induction of oncogenesis and senescence is problematic, mainly with regards to several species specific features like the weight of a dog or its breed. Moreover, the association between the activity of the immunological system and oncogenesis in a dog in an age-dependent manner is also unclear. Studies have suggested that the main factors which influence the process of senescence and oncogenesis are: DNA damage, spontaneous mutations, increase of oxidative stress and decrease of immunological system activity. In this article, the mechanisms and factors associated with oncogenesis and canine senescence have been presented. The authors have also described the role of selected proteins in the induction of these processes.
9

Polymorphism of MTHFR, MTR and MTHFD1 as related to the oxidative DNA damage, and the level of thiols in Alzheimer's and Parkinson’s diseases

64%
Florczak J., Dorszewska J., Rozycka A., Kempisty B., Chojnacka K., Jaroszewska-Kolecka J., Trzeciak W. H., Kozubski W.
Acta Neurobiologiae Experimentalis
|
2006
|
tom 66
|
nr 4
10

Elevated expression of alpha7 neuronal nicotinic acetylcholine receptor during the early stages of damage by oxidative stress in the aging rat brain

64%
Dorszewska J., Rozycka A., Helias-Rodzewicz Z., Kempisty B., Grzelak T., Ziemnicka K., Oczkowska A., Steinborn B., Jagodzinski P.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
Aging is accompanied by a high level of oxidized form of guanine, 8-oxo-2’deoxyguanosine (8-oxo-2’dG), and decreased level of 8-oxoguanine glycosylase 1 (OGG1) in the brain. The development and progression of neurodegenerative disorders are also characterized by dysfunction or loss of the brain nicotinic acetylcholine receptors (nAChRs). To study whether the differences in nAChRs expression in the rat brain occur due to aging or oxidative stress we analyzed RNA and protein levels of α7, α4 and β2 subunits by RQ-PCR and Western blot validation in three brain structures: cerebral grey matter (CGM), sub-cortical white matter (SCWM) and cerebellum (Ce) of twenty one female Wistar rats. The first group consisted of five 3.0–3.5-month-old females, which was assigned as a young control group. The remaining sixteen females aged of 18–24 month were divided into three following groups: (1) aged control group of 5 rats; (2) a vehicle group of 5 rats which received intraperitoneal injections of deionized water; (3) memantine-treated group of 6 rats. In each group, the selected brain areas have also been analyzed to determinate the levels of oxidative stress. In this study, age- and stress- dependent differential RNA and protein expression levels were approved only in OGG1 and α7 nAChR proteins. In all analyzed brain structures of young and old controls, the levels of oxidized form of guanine were similar. Stress relevant to water injection increased the level of 8-oxo-2’dG in the cerebellum of old control rats (Ce, P<0.05). The old controls demonstrated an important reduction of OGG1 mRNA expression in CGM and Ce regions compared to young individuals (CGM P=0.03; Ce P=0.2). Western blot analysis has also revealed a reduction of OGG1 protein in the sub-cortical white matter of old individuals (SCWM, P=0.03). However, there was no important influence of water administration on OGG1 expression in all brain regions. In all analyzed brain structures, expression of α7 nAChR was down-regulated in old controls compared to young controls. However, this decrease was only significant in SCWM area (SCWM, P<0.05). Treatment with H2O caused a significant increase in RNA and protein levels of α7 nAChR in SCWM as compared to this brain structure of the aged control rats (SCWM, P<0.01). Our results suggest that aging of the rat brain is mostly associated with decreased expression of OGG1 as well as with deficit of α7 nAChR in the sub-cortical white matter. Stress relevant to water injection increases the level of 8-oxo-2’dG in the aging rat brain, but clearly overcomes the α7 nAChR deficit. A significant increase of the α7 nAChR expression in the SCWM of H2O-treated rats suggests that these receptors play an important role in compensatory mechanisms facilitating the impaired cholinergic neurotransmission following oxidative stress in the aging rat brain.
11

The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on individual differences in propofol pharmacokinetics among Polish patients undergoing general anaesthesia

64%
Mikstacki A., Zakerska-Banaszak O., Skrzypczak-Zielinska M., Tamowicz B., Prendecki M., Dorszewska J., Molinska-Glura M., Waszak M., Slomski R.
Journal of Applied Genetics
|
2017
|
tom 58
|
nr 2
12

SNCA, PARK2 and LRRK-2 mutations in Polish patients with sporadic Parkinson’s disease

64%
Polrolniczak A., Dorszewska J., Florczak J., Owecki M., Rozycka A., Rubis B., Jagodzinski P. P., Kozubski W.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders in Poland. Although the genetic basis of familial PD is now well established, the majority of PD is sporadic and occurs without a clear mode of inheritance. The etiology of sporadic PD remains unknown, but it is currently assumed that genetic susceptibilities may be involved. The observation that mutations in α-synuclein (SNCA), parkin (PARK2)and leucine-rich repeat kinase 2 (LRRK2) genes are common in familial PD and increasing evidence supporting a direct role for PARK2 and LRRK-2 in sporadic both early- and late-onset disease make those genes a particularly compelling candidate for intensified investigation. The aim of the study was analysis and identification of SNCA, PARK2 and LRRK-2 mutation in Polish patients with sporadic PD. Peripheral blood was collected from 34 patients with sporadic PD clinical diagnosis (the average age 58 years), and 22 patients with the other neurological diseases (the average age 55 years) as well as from 25 healthy donors (the average age 60 years). Genomic DNA was isolated using standard protocols. SNCA mutations analysis was performed to exclude one of the familial forms of PD. Restriction-enzyme digestion of polymerase-chain reaction (PCR) amplified genomic DNA fragment of SNCA exon 3 detected no G88C mutation. PCR-amplification of parkin exons 2 and 4 also detected no exon deletion. Moreover exon 41 of LRRK-2 gene as well as exons 4, 7 and 11 of PARK2 gene was screened using realtime PCR/HRM and exon sequencing. None of the patients as well as control subjects tested had mutation of LRRK2 gene. These results are consistent with previous reports in the Polish population Mutation in tested exons of PARK2 gene were identified in 20,6% patients with sporadic PD, 4,5% patients with the other neurological disorders and 4,0% control subjects. All detected mutations were heterozygous. One of the PD patients had two mutations in PARK2 gene (G1281A, G601A). It can be concluded, that both G88C SNCA and G2019S LRRK-2 mutations as well as deletion of 2 and 4 exon of parkin gene are rare causes of PD in Poland. Moreover point mutation in PARK2 seems to be associated with sporadic PD in polish population. Thus, the results of this study suggest that screening for PARK2 mutations may be a component of genetic testing for sporadic PD.
13

Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer's and Parkinson's diseases

64%
Dorszewska J., Florczak J., Rozycka A., Kempisty B., Jaroszewska-Kolecka J., Chojnacka K., Trzeciak W. H., Kozubski W.
Acta Neurobiologiae Experimentalis
|
2007
|
tom 67
|
nr 2
Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are accompanied by increased levels of 8-oxo-2'deoxyguanosine (8-oxo2dG) and alterations in levels of homocysteine (Hcy), methionine (Met), and cysteine (Cys). Hcy may undergo remethylation due to involvement of MTHFR, MTR and MTHFD1 proteins. Present studies are aimed at determination of 8-oxo2dG, Hcy, Met, and Cys in AD and PD patients as well as in control groups, using HPLC/EC/UV, as well as estimation, by restriction analysis, frequency of following gene polymorphisms: MTHFR (C677T, A1298C, G1793A), MTHFD1 (G1958A), and MTR (A2756G). In AD there were significant differences of the levels of only Cys (GG, MTHFR, G1793A) and Met/Hcy (AA, MTHFD1, G1958A) whereas in PD there were more significant differences of the levels of thiols: Hcy [MTHFR: CT (C677T) and GG (G1793A); MTR, AG (A2756G)], Met [MTR, AA (A2756G)], Cys [MTR, AG (A2756G)], and Met/Hcy [MTHFR: CC, CT (C677T) and AA (A1298C), and GG (G1793A); MTHFD1 AA (G1958A); MTR AA (A2756G)]. Significant differences in the levels of Cys/Hcy, MTHFD1 GA (G1958) were varied between AD and PD groups. The results indicate that of the enzymes studied only polymorphisms of folate-dependent enzyme MTHFD1 have pointed to significant differences in intensity of turnover of circulating thiols between AD and PD patients.
14

Memantine up-regulates nicotinic acetylcholine receptors expression in the cortex and sub-cortical white matter of aging rat brain

64%
Polrolniczak A., Rozycka A., Helias-Rodzewicz Z., Kempisty B., Grzelak T., Ziemnicka K., Steinborn B., Jagodzinski P. P., Dorszewska J.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
Memantine (MEM) is a potent open channel blocker of N-methyl-Daspartate receptors (NMDARs), and primary has been developed for treatment of neuropathic pain, symptoms of dementia and AD. On the other hand, MEM is able to act as an open channel blocker on several other ligand gated ion channels, e.g., the α4β2 and α7 nicotinic acetylcholine receptors (nAChRs). The aged-related decline in the nAChRs expression could be associated with other senescence markers, such as increased oxidative stress leading to oxidative DNA changes (high level of 8-oxo-2’dG), accompanied with significant decrease in level of the OGG1 protein involved in DNA repair process. To study whether MEM treatment might influence on the α7 and α4 nAChRs expression in the aging rat brain tissues, we analyzed RNA and protein levels by RQ-PCR and Western blot validation in three brain structures: cerebral grey matter (CGM), sub-cortical white matter (SCWM) and cerebellum (Ce) of twenty one female Wistar rats. The animals were divided into following experimental groups: the first group consisted of five 3.0–3.5-month-old females, which was assigned as a young control group, and the remaining sixteen females aged of 18–24 month were divided into three following sub-groups: (1) aged control group of 5 rats; (2) a vehicle group of 5 rats which received intraperitoneal injections of deionized water (3) memantine-treated group of 6 rats. In each group, the selected brain areas have also been analyzed to determinate the levels of oxidative stress. In CGM and SCWM brain structures the level of 8-oxo-2’dG was significantly reduced in old rats after MEM administration (CGM P=0.05; SCWM P<0.05). Western blot analysis has also revealed a significant up-regulation of OGG1 level in CGM after MEM administration (CGM P=0.05). MEM specifically up-regulated mRNA level of cortical α4 subunit in the CGM region of aging rat brain (CGM, P<0.05). In the sub-cortical white matter an important increase of α7 mRNA level has been observed after MEM administration (SCWM P<0.05). The level of α7 nAChR protein was significantly up-regulated also in CGM and Ce regions of MEM treated rats (SCWM P=0.05; CGM P<0.05; Ce P<0.05). We demonstrated that processes related to aging, such as a decreases in OGG1 and nAChRs expression can be modified after memantine administration: (1) A significant increase in the CGM of α4 and α7 subunits, as well as up-regulated α7 level in the SCWM after MEM administration suggests that nAChRs play an important role in compensatory mechanisms facilitating the impaired cholinergic neurotransmission following treatment with MEM. (2) MEM significantly up-regulates cortical OGG1 protein expression and reduces the level of 8-oxo-2’dG in CGM. (3) A significant increase in both mRNA and protein levels of α7 nAChR along with reduction of 8-oxo-2’dG in SCWM, following treatment with MEM, suggests that the effect of MEM on cholinergic function may be associated with antioxidant mechanisms. Whether these protective effects of MEM are direct or are mechanistically remote from NMDARs antagonism, have to be evaluated in the further studies.
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