Chronic restraint stress impairs spatial memory while decreasing hippocampal BDNF levels in rats

Aim: This study investigated the potential role of chronic restraint stress (CRS) on spatial memory, recognition memory, brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels in young adult rats. Material and Methods: In the study, 16 female rats of 12 weeks old were used. Rats were divided into two groups as control and CRS (n=8). CRS was applied 5 hours a day for 21 days. Following the end of CRS, recognition memory of rats was evaluated with new object recognition test (NORT) and spatial memory was evaluated with Morris water maze (MWM) test. At the end of the study, rats were euthanized and hippocampal tissue homogenates were obtained. Hippocampal BDNF and ACh levels were determined by ELISA method. Results: Exposure to CRS did not significantly change the exploratory behavior and discrimination index of rats (p > 0.05). In the test phase in which spatial memory was evaluated, CRS decreased the time spent in the target quadrant (p > 0.01). There was no significant difference between days in the training phase. CRS significantly decreased BDNF level in hippocampus (p > 0.05). Hippocampal ACh levels were not statistically significant (p > 0.05). Conclusions: CRS weakened cognitive functions in rats. This effect was mainly accompanied by a decrease in hippocampal BDNF levels. Our findings point to the potential role of BDNF in understanding the molecular mechanism of CRS-induced cognitive impairment

Agomelatin yetişkin sıçanlarda skopolamin kaynaklı öğrenme ve hafıza bozukluğunu tersine çevirir

Amaç: Agomelatin, melatonin reseptör (MT1 ve MT2) agonisti ve serotonin reseptör (5-HT2C) antagonisti olan antidepresan bir ilaçtır. Artan kanıtlar, agomelatinin nöroprotektif ve nöromodülatör etkiye sahip olduğunu göstermektedir. Bu çalışmada skopolamin indüklü bilişsel yetmezlik oluşturulan sıçanlarda agomelatinin potansiyel etkileri araştırılmıştır. Materyal ve Metot: Erişkin erkek sıçanlara 21 gün süreyle skopolamin (1 mg/kg) ve agomelatin (40 mg/kg) uygulandı. İlaç uygulamalarını takiben sıçanlar bilişsel davranışların değerlendirilebilmesi amacıyla yeni nesne tanıma (YNT) ve Morris su labirenti (MSL) testine tabi tutuldu. İlave olarak, beyin nörokimyasal analizleri için hipokampus ve prefrontal kortekste beyin-türevi nörotrofik faktör (BDNF) ve asetilkolin (ACh) düzeyleri değerlendirildi. Bulgular: Skopolamin hem uzamsal hafızayı hem de ayırt etme indeksini önemli ölçüde azalttı (p<0,05). Agomelatin tedavisi uzamsal hafıza performansını ve keşif süresini arttırdı, ancak ayrımcılık indeksini etkilemedi (P>0,05). Ayrıca agomelatin, skopolamin grubuna kıyasla hem hipokampusta hem de prefrontal kortekste BDNF düzeylerini önemli ölçüde arttırdı (sırasıyla p<0,05, p<0,01). Diğer yandan grupların ACh düzeyleri arasında istatistiksel olarak anlamlılık bulunmadı (p>0,05). Sonuç: Birlikte ele alındığında, bu sonuçlar agomelatinin skopolamin kaynaklı hafıza yetmezliğinin hafifletilmesinde belirgin rol oynadığını göstermiştir. Bu nedenle, agomelatinin bilişsel yetmezliğin önlenmesinde potansiyel bir ajan olabileceğini öne sürüyoruzObjective: The antidepressant agomelatine agent is a melatonin receptor (MT1 and MT2) agonist and a serotonin receptor (5-HT2C) antagonist. Increasing evidence shows that agomelatine has neuroprotective and neuromodulatory effects. In this study, the potential effects of agomelatine in rats with scopolamine-induced cognitive impairment were investigated. Materials and Methods: Adult male rats were administered scopolamine (1 mg/kg) and agomelatine (40 mg/kg) for 21 days. After drug administration, rats were subjected to new object recognition (NOR) and Morris water maze (MWM) tests in order to evaluate cognitive behaviors. In addition, brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels in the hippocampus and prefrontal cortex were evaluated. Results: Scopolamine significantly decreased both spatial memory and discrimination index (p<0.05). Agomelatine treatment increased spatial memory performance and exploration time, but did not affect the discrimination index (P>0.05). In addition, agomelatine significantly increased BDNF levels in both hippocampus and prefrontal cortex compared to the scopolamine group (p<0.05, p<0.01, respectively). On the other hand, there was no statistically significant difference between the ACh levels of the groups (p>0.05). Conclusion: Taken together, these results demonstrated that agomelatine plays a important role in alleviating scopolamine-induced memory impairment. Therefore, we suggest that agomelatine may be a potential agent in the prevention of cognitive impairment

Intersection problem for Droms RAAGs

We solve the subgroup intersection problem (SIP) for any RAAG G of Droms type (i.e., with defining graph not containing induced squares or paths of length 3): there is an algorithm which, given finite sets of generators for two subgroups H,K of G, decides whether $H \cap K$ is finitely generated or not, and, in the affirmative case, it computes a set of generators for $H \cap K$. Taking advantage of the recursive characterization of Droms groups, the proof consists in separately showing that the solvability of SIP passes through free products, and through direct products with free-abelian groups. We note that most of RAAGs are not Howson, and many (e.g. F_2 x F_2) even have unsolvable SIP.Comment: 33 pages, 12 figures (revised following the referee's suggestions

Effects of geraniol on anxiety/depression-like behavior and hippocampal cholinergic system in rats

Amaç: Kronik stresin depresyon benzeri davranışları arttırdığı bilinmektedir. Geraniol nöromodülatör ve antidepresan etkileri bilinen doğal bir monoterpendir. Bu çalışma, kronik kısıtlama stresi depresyon modeli sıçanlarda geraniolun kolinerjik sistem üzerine olası etkilerini araştırmak için tasarlanmıştır. Gereç ve Yöntem: Çalışmada erişkin 21 adet dişi sıçan kullanıldı. Sıçanlara 3 hafta süreyle günde 5 saat kısıtlama stresi uygulandı. Geraniol oral gavaj yoluyla 100 mg/kg uygulandı. Stres ve ilaç uygulamalarını takiben açık alan testi ile anksiyete, zorunlu yüzme testi ile depresyon benzeri davranışlar değerlendirildi. Daha sonra sıçanlar ötenazi edilerek hipokampus disekte edildi. Asetilkolin (ACh) ve asetilkolinesteraz (AChE) düzeyleri hipokampal doku homojenatlarında ELISA yöntemi ile belirlendi. Bulgular: Stres maruziyeti anksiyete benzeri davranışı belirgin olarak etkilemedi ancak zorunlu yüzme testlerinde depresyon benzeri davranış parametrelerini uyardı. Geraniolun strese bağlı artan hareketsizlik süresini önemli ölçüde azalttığı tespit edildi (p<0.05). Dahası, stres maruziyeti ve geraniol uygulamasının hipomkampal ACh düzeylerini anlamlı olarak etkilemediği gözlemlendi (p>0.05). Diğer yandan, kronik stres AChE düzeylerini önemli ölçüde azalttı (p<0.05). Geraniol tedavisinin AChE düzeylerini belirgin olarak değiştirmediği tespit edildi (p>0.05). Sonuç: Birlikte ele alındığında, bulgularımız kısıtlama stresinin sıçanlarda depresyon benzeri davranışı uyardığı, geraniol tedavisinin ise antidepresan benzeri etkilerini ortaya koydu. Bununla birlikte, geraniolun antidepresan benzeri etkisinin moleküler mekanizmasının ileri çalışmalarla araştırılmasını öneriyoruz.Objective: It is known that chronic stress increases depression-like behaviors. Geraniol is a natural monoterpene known for its neuromodulatory and antidepressant effects. This study was designed to investigate the possible effects of geraniol on the cholinergic system in chronic restraint stress depression model rats. Materials and Methods: 21 adult female rats were used in the study. Restraint stress was applied to rats for 5 hours a day for 3 weeks. Geraniol was administered at 100 mg/kg by oral gavage. Anxiety was evaluated with the open field test, and depression-like behaviors were evaluated with the forced swimming test following stress and drug administration. Then the rats were euthanized and the hippocampus was dissected. Acetylcholine (ACh) and acetylcholinesterase (AChE) levels were determined in hippocampal tissue homogenates by ELISA method. Results: Stress exposure did not significantly affect anxiety-like behavior, but it stimulated depression-like behavior parameters in forced swimming tests. It was determined that geraniol significantly decreased the increased immobility time due to stress (p<0.05). Moreover, it was observed that stress exposure and geraniol administration did not significantly affect hippocampal ACh levels (p>0.05). On the other hand, chronic stress significantly decreased AChE levels (p<0.05). Geraniol treatment did not significantly change AChE levels (p>0.05). Conclusion: Taken together, our findings revealed that restraint stress induces depression-like behavior in rats, while geraniol treatment has antidepressant-like effects. However, we suggest that the molecular mechanism of the antidepressant-like effect of geraniol be investigated with further studies

Utility of a Sequence-Independent, Single-Primer-Amplification (SISPA) and Nanopore Sequencing Approach for Detection and Characterization of Tick-Borne Viral Pathogens

Currently, next generation sequencing (NGS) is the mainly used approach for identification and monitorization of viruses with a potential public health threat in clinical and environmental samples. To facilitate detection in NGS, the sequence-independent, single-primer-amplification (SISPA) is an effective tool for enriching virus sequences. We performed a preliminary assessment of SISPA-nanopore sequencing as a potential approach for screening tick-borne viruses in six specimens with detectable Crimean-Congo hemorrhagic fever virus (CCHFV) and Jingmen tick virus (JMTV) sequences. A comparison of unbiased NGS and SISPA followed by nanopore sequencing was carried out in 4 specimens with single and pooled ticks. The approach was further used for genome sequencing in culture-grown viruses. Overall, total/virus-specific read counts were significantly elevated in cell culture supernatants in comparison to single or pooled ticks. Virus genomes could be successfully characterized by SISPA with identities over 99%. Genome coverage varied according to the segment and total read count. Base calling errors were mainly observed in tick specimens and more frequent in lower viral loads. Culture-grown viruses were phylogenetically-related to previously-reported local viruses. In conclusion, the SISPA + nanopore sequencing was successful in generating data comparable to NGS and will provide an effective tool for broad-range virus detection in ticks.Peer Reviewe

Concurrent occurrence of human and equine West Nile virus infections in Central Anatolia, Turkey: the first evidence for circulation of lineage 1 viruses

SummaryBackgroundWest Nile fever is an important zoonotic infection caused by West Nile virus (WNV), a member of the Flaviviridae. Previous serological data from Turkey suggest widespread WNV circulation. This report includes cases of human and equine WNV infections occurring concurrently, and manifesting as central nervous system infections, in two neighboring provinces of Central Anatolia, Turkey. A partial phylogenetic analysis of the causative virus is given for the first time.MethodsThe cases were reported in February (horses) and March (human). Symptoms of the disease were similar in the two species, characterized by neurological manifestations suggesting meningoencephalitis. Real-time/nested PCRs and commercial immunoassays and a plaque reduction neutralization assay were employed for the detection of viral RNA and specific antibodies, respectively.ResultsWNV RNAs were detected in buffy coat (horses) and cerebrospinal fluid (human) samples. Partial nucleotide sequences of the E-gene coding region revealed that the strains are closely related to viruses of lineage 1, clade 1a. Accompanying equine serosurveillance demonstrated WNV-specific antibodies in 31.6% of the samples.ConclusionsThis is the first report of acute WNV infections caused by lineage 1 strains from Turkey, in concordance with previous reports from some European and North African countries

Karadeniz ve Akdeniz tsunamileri için model geliştirme ve risk analizi projesi

TÜBİTAK ÇAYDAG15.07.201

Multi-assay investigation of viral etiology in pediatric central nervous system infections

Introduction: In an attempt to identify a wide spectrum of viral infections, cerebrospinal fluid (CSF) specimens were collected from pediatric cases with the preliminary diagnosis of viral encephalitis/meningoencephalitis in two reference hospitals, from October 2011 to December 2015. Methodology: A combination of nucleic acid-based assays, including in house generic polymerase chain reaction (PCR) assays for enteroviruses, flaviviruses and phleboviruses, a commercial real-time PCR assay for herpesviruses and a commercial real time multiplex PCR, enabling detection of frequently-observed viral, bacterial and fungal agents were employed for screening. Results: The microbial agent could be characterized in 10 (10%) of the 100 specimens. Viral etiology could be demonstrated in 7 (70%) specimens, which comprises Human Herpesvirus 6 (4/7), Herpes Simplex virus type1 (2/7) and Enteroviruses (1/7). In 3 specimens (30%), Streptococcus pneumoniae, Listeria monocytogenes and Staphylococcus aureus were detected via the multiplex PCR, which were also isolated in bacteriological media. All specimens with detectable viral nucleic acids, as well as unreactive specimens via nucleic acid testing remained negative in bacteriological cultures. Conclusions: Herpes and enteroviruses were identified as the primary causative agents of central nervous system infections in children. Enterovirus testing must be included in the diagnostic work-up of relevant cases

Co-circulation of West Nile virus and distinct insect-specific flaviviruses in Turkey

Background: Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to investigate the circulation of flaviviruses. Mosquitoes were collected from 58 locations in 10 provinces across the Aegean, Thrace and Mediterranean Anatolian regions of Turkey in 2014 and 2015. Following morphological identification, mosquitoes were pooled and screened by nested and real-time PCR assays. Detected viruses were further characterised by sequencing. Positive pools were inoculated onto cell lines for virus isolation. Next generation sequencing was employed for genomic characterisation of the isolates. Results: A total of 12,711 mosquito specimens representing 15 species were screened in 594 pools. Eleven pools (2%) were reactive in the virus screening assays. Sequencing revealed West Nile virus (WNV) in one Culex pipiens (s.l.) pool from Thrace. WNV sequence corresponded to lineage one clade 1a but clustered distinctly from the Turkish prototype isolate. In 10 pools, insect-specific flaviviruses were characterised as Culex theileri flavivirus in 5 pools of Culex theileri and one pool of Cx. pipiens (s.l.), Ochlerotatus caspius flavivirus in two pools of Aedes (Ochlerotatus) caspius, Flavivirus AV-2011 in one pool of Culiseta annulata, and an undetermined flavivirus in one pool of Uranotaenia unguiculata from the Aegean and Thrace regions. DNA forms or integration of the detected insect-specific flaviviruses were not observed. A virus strain, tentatively named as “Ochlerotatus caspius flavivirus Turkey”, was isolated from an Ae. caspius pool in C6/36 cells. The viral genome comprised 10,370 nucleotides with a putative polyprotein of 3,385 amino acids that follows the canonical flavivirus polyprotein organisation. Sequence comparisons and phylogenetic analyses revealed the close relationship of this strain with Ochlerotatus caspius flavivirus from Portugal and Hanko virus from Finland. Several conserved structural and amino acid motifs were identified. Conclusions: We identified WNV and several distinct insect-specific flaviviruses during an extensive biosurveillance study of mosquitoes in various regions of Turkey in 2014 and 2015. Ongoing circulation of WNV is revealed, with an unprecedented genetic diversity. A probable replicating form of an insect flavivirus identified only in DNA form was detected