Effect of chronic administration and withdrawal of caffeine on motor function, cognitive functions, anxiety, and the social behavior of BLC57 mice.

OBJECTIVES: The cognitive functions, motor coordination, and social behavior were studied in rodents after adding different doses of caffeine in their drinking water. METHODOLOGY: BLC57 mice were divided into four groups: Control (n = 8), chronic moderate dose (n = 8, Ch] MD), Ch high dose (n = 8, Ch HD), and withdrawal (n = 8, WD). Caffeine was administered for 1 month to all groups. Spatial memory was tested by Morris water maze, motor coordination by rotarod (RR), social behavior by (Crawley's test), and anxiety by elevated plus maze (EPM) test. RESULTS: In water maze, the latency to reach the platform was significantly shorter in Ch MD group compared to the control and the Ch HD groups. WD group showed the worst performance. RR results showed that the groups treated with caffeine performed poor in comparison to the control group where their latency to fall was significantly less. In the three-chamber test, the Ch MD group showed enhanced sociability (session 1) and social novelty behavior (session 2). On the other hand, both Ch HD and WD showed a lack in sociability and a deficit in social novelty. In the EPM, results showed that all caffeine administrated mice where more anxious than the control group. CONCLUSION: We concluded that chronic administration of caffeine in MD resulted in enhancement of spatial memory, motor functions, sociability, and social novelty. The anxiety in these animals was, however, increased. On the other hand, Ch HD caffeine had opposite effects on all the parameters except for anxiety.

Acute Administration of Caffeine: The Effect on Motor Coordination, Higher Brain Cognitive Functions, and the Social Behavior of BLC57 Mice.

Excessive caffeine consumption causes adverse health effects. The effects of moderate and high doses of caffeine consumption on the motor coordination, cognitive brain functions, and the social behavior in mice were studied. Animals were divided into three groups: control group, moderate dose group (Ac MD), and high dose group (Ac HD). The animals were tested after 7 days of caffeine administration. A rotarod test for motor coordination showed that the mice of the moderate dose group could stay on the rotating rod longer before falling in comparison to the control group and the high dose group. A water maze test for learning and memory showed better performance of mice receiving the moderate dose of caffeine compared to the other groups. Animals that were administered moderate as well as high doses of caffeine showed no sociability and no preference for social novelty in the three-chamber test used to test social behavior. In an elevated plus maze test, control animals showed no anxiety-like behavior while mice from both of the groups administered with caffeine showed anxiety-like behaviors. Our data conclude that the effects of caffeine on higher brain functions depend on the administration dose. When caffeine was given in moderate doses, it resulted in enhancement of memory and motor coordination functions. However, high doses caused defects in memory and learning. The social behavior of the mice, as determined by the level of anxiety and sociability, was affected negatively by moderate as well as high dose caffeine administration.

Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients.

BACKGROUND: Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC), a common primary liver malignancy, and the third leading cause of cancer-related death. The HCC risk increases with the severity of liver inflammation, and the clinical course of HCV infection depends on a balance between pro- and anti-inflammatory cytokines. The former includes interleukin (IL)-6, while the latter includes IL-10. However, the exact pathogenic mechanisms underlying IL-6 and IL-10 effects remain unclear. METHODS: The present study evaluated 174 chronic HCV Tunisian patients. Polymorphisms of IL-6 (rs1880242, rs1474847, rs2069840, rs1800797, rs1800796, rs2069845, rs2069827, rs1474348, rs1800795), and IL-10 (rs1800896, rs1800871, rs1800872, rs1554286, rs1878672, rs1518111) were determined by real-time PCR. RESULTS: Notable differences between chronic HCV-infected patients and HCC patients were observed for the three IL-10 SNPs; rs1800871 (-819T/C), rs1800872 (-592A/C), and rs1878672. Carriage of IL-6 rs1800796 G/G genotype, IL-6 rs1474358 C-allele, and IL-6 rs1800797 A-allele was more frequent in chronic HCV-infected patients than in HCC patients. On the other hand, IL-6 rs1474358 GG genotype had a favourable factor for HCC establishment. CONCLUSION: IL-10 and IL-6 SNPs markedly influence the clinical outcomes of HCV infection. These SNPs could be used as biomarkers for early detection and molecular therapy for preventing HCC, and prognostic factors for predicting the clinical outcomes of HCC.

Relationships between Common and Novel Interleukin-6 Gene Polymorphisms and Risk of Cervical Cancer: a Case-Control Study.

We investigated the association between six common and novel interleukin-6 (IL-6) polymorphisms with the risk of cervical cancer (CC) among Tunisians. Study subjects comprised 112 CC cases and 164 control women. Genotyping of IL-6 rs2069845, rs2069840, rs1474348, rs1800795, rs1800797, rs2069827 variants was done by real-time PCR, with defined clusters. The allelic and genotypic distributions of the tested IL-6 SNPs were comparable between CC patients and control women. Stratification according to FIGO staging revealed that rs1800795 homozygous major allele genotype (P = 0.033; OR =0.49(0.25-0.95)) and major allele (P = 0.037; OR = 0.57 (0.33-0.97)) were protective of CC. Moreover, carriage of rs1474348 major allele was also protective of CC (P = 0.014; OR = 0.53(0.32-0.88)), while higher rs1474348 minor allele frequency was seen in CC patients with early FIGO stage (P = 0.044; OR = 0.39 (0.15-1.00)), thus implicating rs1474348 in CC evolution and progression of angiogenesis. Haploview analysis demonstrated high linkage disequilibrium (LD) between rs2069845, rs2069840, rs1474348 and rs1800795, and 6-locus haplotype analysis identified GACCCA haplotype to be positively associated with increased CC, while GAGGGG haplotype was negatively associated with CC, thus suggesting a protective role for this haplotype in CC. Furthermore, there was a significant association between the incidence of CC and the use hormonal contraception (P = 0.047; OR = 1.97 (0.94-4.13)) and smoking (P < 0.001; OR = 7.12 (2.97-17.04)). The IL-6 variants rs1800795 and rs1474348, and haplotypes GACCCA and GAGGGG, along with use of hormonal contraceptives and smoking, are major risk factors of CC susceptibility and evolution among Tunisian women.

Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms in Cervical Cancer Risk.

For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46-17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01-0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.