Alzheimer's disease (AD) is the most common form of progressively disabling dementia. The chitinases CHI3L1 and CHI3L2 have long been known as biomarkers for microglial and astrocytic activation in neurodegeneration. Here, we collected microarray datasets from the National Center for Biotechnology Information (NCBI) brain samples of non-demented controls (NDC) (n = 460), and of deceased patients with AD (n = 697). The AD patients were stratified according to sex. Comparing the high CHI3L1 and CHI3L2 expression group (75th percentile), and low CHI3L1 and CHI3L2 expression group (25th percentile), we obtained eight signatures according to the sex of patients and performed a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to twelve cell populations. Expression analysis revealed significantly higher CHI3L1 and CHI3L2 expression in AD compared with NDC, and positive correlations of these genes with GFAP and TMEM119. Furthermore, deconvolution analysis revealed that CHI3L1 and CHI3L2 high expression was associated with inflammatory signatures in both sexes. Neuronal activation profiles were significantly activated in AD patients with low CHI3L1 and CHI3L2 expression levels. Furthermore, gene ontology analysis of common genes regulated by the two chitinases unveiled immune response as a main biological process. Finally, microglia NIS significantly correlated with CHI3L2 expression levels and were more than 98% similar to microglia NIS determined by CHI3L1. According to our results, high levels of CHI3L1 and CHI3L2 in the brains of AD patients are associated with inflammatory transcriptomic signatures. The high correlation between CHI3L1 and CHI3L2 suggests strong co-regulation.
- MeSH
- Alzheimerova nemoc * genetika metabolismus MeSH
- biologické markery metabolismus MeSH
- chitinasy * genetika metabolismus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- transkriptom genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Neurological complications of AIDS (NeuroAIDS) include primary HIV-associated neurocognitive disorder (HAND). OAS3 is an enzyme belonging to the 2', 5' oligoadenylate synthase family induced by type I interferons and involved in the degradation of both viral and endogenous RNA. Here, we used microarray datasets from NCBI of brain samples of non-demented HIV-negative controls (NDC), HIV, deceased patients with HAND and encephalitis (HIVE) (treated and untreated with antiretroviral therapy, ART), and with HAND without HIVE. The HAND/HIVE patients were stratified according to the OAS3 gene expression. The genes positively and negatively correlated to the OAS3 gene expression were used to perform a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to sixteen signatures. Expression analysis revealed significantly higher OAS3 expression in HAND/HIVE and HAND/HIVE/ART compared with NDC. OAS3 expressed an excellent diagnostic ability to discriminate NDC from HAND/HIVE, HAND from HAND/HIVE, HAND from HAND/HIVE/ART, and HIV from HAND/HIVE. Noteworthy, OAS3 expression levels in the brains of HAND/HIVE patients were positively correlated with viral load in both peripheral blood and cerebrospinal fluid (CSF). Furthermore, deconvolution analysis revealed that the genes positively correlated to OAS3 expression were associated with inflammatory signatures. Neuronal activation profiles were significantly activated by the genes negatively correlated to OAS3 expression levels. Moreover, gene ontology analysis performed on genes characterizing the microglia signature highlighted an immune response as a main biological process. According to our results, genes positively correlated to OAS3 gene expression in the brains of HAND/HIVE patients are associated with inflammatory transcriptomic signatures and likely worse cognitive impairment.
- MeSH
- 2',5'-oligoadenylátsynthetasa genetika metabolismus MeSH
- HIV infekce * komplikace MeSH
- HIV * genetika metabolismus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- neurokognitivní poruchy komplikace metabolismus MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Human behavior is influenced by both genetic and environmental factors. Monoamine oxidase A (MAOA) is among the most investigated genetic determinants of violent behaviors, while the monoamine oxidase B (MAOB) is explored in Parkinson's disease. We collected twenty-four post-mortem brain tissue datasets of 3871 and 1820 non-demented males and females, respectively, who died from causes not attributable to neurodegenerative diseases. The gene expressions of MAOA and MAOB (MAO genes) were analyzed in these subjects, who were further stratified according to age into eleven groups ranging from late Infancy (5-9 months) to centenarians (>100 years). MAO genes were differently expressed in brains during the entire life span. In particular, maximal and minimal expression levels were found in early life and around the teen years. Females tended to have higher MAO gene levels throughout their lives than those found in age-matched males, even when expressions were separately measured in different brain regions. We demonstrated the existence of age- and sex- related variations in the MAO transcript levels in defined brain regions. More in-depth protein studies are needed to confirm our preliminary results obtained only on messenger RNAs in order to establish the role played by MAO genes in human development.
- MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- monoaminoxidasa biosyntéza MeSH
- mozek enzymologie MeSH
- novorozenec MeSH
- pohlavní dimorfismus * MeSH
- předškolní dítě MeSH
- regulace genové exprese enzymů * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
To improve the knowledge in chronophysiology we investigated the causal link between the most important physiological variable studied until now; ten Sarda ewes and ten Sarda goats, pluriparus not pregnant and no lactating, were used. Animals were housed under natural environmental conditions in a common stall, alfalfa hay and water were available ad libitum. Each animal was equipped with an Actiwatch-Mini® for recording total activity. Blood samples were collected every 4 h over a 48 h period for the assessment of melatonin concentration. Rectal temperature was recorded with a digital thermometer immediately before the blood sampling at each data point. Single cosinor method showed a daily rhythm of studied variables. Higher MESOR and amplitude values of melatonin and rectal temperature were observed in sheep than in goats. The diurnal acrophase of locomotor activity was statistically different from the nocturnal acrophase of melatonin and rectal temperature, with no differences between the two species. Robustness was statistically lower in total locomotor activity in comparison with the others two variables, with a differences due to species in melatonin daily rhythm. In conclusion, in small ruminants, melatonin and rectal temperature daily rhythms are strictly correlated, and are not associated with the locomotor activity rhythm.
To evaluate parallel circadian rhythms in salivary and serum cortisol concentrations during 48-h period, sampling was performed in six clinically healthy dogs of various breeds housed under natural photoperiod in spring (sunrise 05:20, sunset 20:20). Saliva and blood samples were taken every 3 h for a 48-h period to determine the daily changes in salivary and serum cortisol concentrations. The relationship between salivary and serum cortisol level was determined as well. In the two-day period of monitoring, salivary and serum cortisol concentrations showed the same trend. Their levels started to increase at sunrise and reached their peak in the middle of the photophase. Both parameters showed a high robustness of rhythm. A positive correlation between salivary and serum cortisol concentration was observed during the day 1 and 2. Acrophase and robustness of rhythm showed no statistically significant difference between salivary and serum cortisol concentrations. We can claim that salivary cortisol, a measure of free cortisol, follows the circadian rhythm of serum cortisol. Therefore, saliva sampling is a valid and non-invasive technique useful in chronomedicine to estimate free cortisol.
- MeSH
- cirkadiánní rytmus * fyziologie MeSH
- hydrokortison * analýza fyziologie krev MeSH
- psi fyziologie krev MeSH
- sérum fyziologie MeSH
- sliny fyziologie MeSH
- statistika jako téma MeSH
- zvířata MeSH
- Check Tag
- psi fyziologie krev MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
Cortisol and other adrenal steroids are typically secreted in a pulsate fashion and plasma concentrations can vary widely during a 24-hour period. To investigate daily rhythmicity of plasma adrenocorticotrophin (ACTH) concentration, as well as rectal temperature (RT), sample collections were performed in five Quarter Horses housed in individual boxes under natural light/dark (L/D) cycle followed by constant darkness. The two variables exhibited 24-h rhythmicity under the L/D cycle. Whereas rhythmicity of RT persisted in constant darkness, rhythmicity of ACTH concentration did not. These findings strongly suggested that ACTH secretion in the horse is not under circadian control and is modulated only by environmental light.
This research was carried out on five clinically healthy Sella Italiana horses to determine the daily rhythm of total proteins and their fractions, to establish if these rhythms are endogenously generated and to assess the role of light as synchroniser of these rhythms. Blood samples were collected from each subject every 3 h over a period of 48 h, starting at 9:00 on day 1 and finishing at 9:00 on day 3, into vacutainer tubes without an anticoagulant via intravenous cannulas inserted into the jugular vein. Total serum proteins, albumin, α1-, α2-, β1-, β2- and γ-globulin concentrations were assessed in all samples. The application of two-way ANOVA showed a significant effect of the time of day on total proteins, albumin, β1- and β2-globulins, and of the experimental conditions on total proteins α1-, α2-, β1-, β2- and γ-globulins. No statistical modifications were observed on the A/G ratio. Daily rhythmicity was exhibited only by total proteins and albumin during the L/D cycle. We can claim that the fluctuation of serum total proteins and albumin concentrations are daily and not circadian and that they are driven by the L/D cycle.
- MeSH
- cirkadiánní rytmus fyziologie MeSH
- elektroforéza sérových bílkovin statistika a číselné údaje MeSH
- fotoperioda MeSH
- koně fyziologie krev MeSH
- krevní proteiny fyziologie izolace a purifikace MeSH
- periodicita MeSH
- sérové globuliny fyziologie izolace a purifikace MeSH
- sérový albumin fyziologie izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
The aim of this study was to investigate the nycthemeral rhythm of total locomotor activity (TLA) in horse and the possible involvement of the daily organization of rest/activity cycles in the fluctuation of the redox state. For this purpose we recorded TLA and determined oxidative markers in ten clinically healthy Italian Saddle horses. TLA was continuously recorded by means of an actigraphy-based data logger Actiwatch-Mini®. For the assessment of free radicals (dROMs), the antioxidant barrier (Oxy-ads) and the thiol-antioxydant barrier (SHp), blood samples were collected every 4 hours over a 48 h period. One-way repeated measures analysis of variance (ANOVA) showed a statistically significant effect of time of day on all studied parameters. The application of the periodic model and the statistical analysis of cosinor indicate, in horses, the existence of a daily rhythm of the studied parameters during the 48 h of monitoring of the horses. The results show that nycthemeral rhythms of TLA and oxidative markers have different trends in horse. dROMs and Oxy-ads showed a nycthemeral rhythm with an acrophase in the middle of the photophase, and an acrophase of SHp nycthemeral rhythm preceded them. In contrast, TLA showed its acrophase only after the middle of the photophase. TLA showed a lower robustness of rhythms (16.3 and 20.3%) and in respect to the robustness values of the rhythms of oxidative markers (67.3-86.2%). In conclusion, the results of the present investigation showed that oxidative markers have different patterns than locomotor activity, and further studies could be necessary to determine whether other external stimuli, such as solar radiation, food administration or physical exercise are able to influence redox state rhythms in this species.
The author studied in thirty Thoroughbred horses the influence of age and gender on daily rhythms of serum osteocalcin (OC). The animals were divided into two groups. Group A: six male and six female 2 years old; Group B: six male, six female and six geldings 6 years old. They were housed individually in box-like stalls under natural photoperiod and environmental conditions. Blood samples were collected every 3 hours over a 48 hour period. Statistical differences of serum OC concentration due to different gender were observed in both Groups A and B. Daily rhythms of serum OC concentration were observed only in Group B, with nocturnal acrophase. In females the acrophase was statistically postponed for 1 hour compared to male and gelding. Male and female showed a more robust daily rhythm than the geldings. The results showed that blood sampling for determination of serum OC should be strictly standardized with regard to the time of the day.
- Klíčová slova
- circadian rhythms, osteocalcin, age, gender, horses,
- MeSH
- biologické markery krev metabolismus moč MeSH
- cirkadiánní rytmus fyziologie MeSH
- experimenty na zvířatech normy statistika a číselné údaje MeSH
- koně MeSH
- kosti a kostní tkáň metabolismus MeSH
- odběr vzorku krve metody využití MeSH
- osteokalcin krev moč MeSH
- sexuální faktory MeSH
- statistika jako téma MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
The goal of the present study was to investigate the daily amount of motor activity and the daily rhythm of tryptophan and serotonin in goats housed in individual boxes under a 12/12 light/dark cycle. We equipped six Girgentana breed goats with Actiwatch-Mini® (Cambridge Neurotechnology Ltd, UK), actigraphy-based data loggers that record a digitally integrated measure of motor activity. Also blood samples were collected at four-hour intervals over a 48 h period via an intravenous cannula inserted into the jugular vein. The concentration of tryptophan (TRP) and serotonin (5-HT) were assessed by the high-performance liquid chromatography (HPLC) method. Our results outline a diurnal pattern of motor activity and levels of tryptophan in the serum, and a nocturnal pattern of levels of serotonin in the serum, which underline the impact of endogenous serotoninergic activity on the behavioural aspects of the circadian response to light.