The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.

Idiopathic Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilized human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence dependent on S100A9 and stress factors. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.

Potassium triiodide-quenched gold nanocluster as a fluorescent turn-on probe for sensing cysteine/homocysteine in human serum.

A fluorescent sensing platform using KI3-quenched bovine serum albumin stabilized gold nanoclusters has been designed and used as a fluorescent probe for the turn-on detection of homocysteine/cysteine (Cys/Hcy). The fluorescence of gold nanoclusters was quenched by iodine. The fluorescence of quenched gold nanoclusters was effectively switched on by Cys/Hcy devoid of the interference of glutathione. The transmission electron microscopy image, X-ray photoelectron spectroscopy analysis, time-correlated single photon counting analysis, and dynamic light scattering data confirmed the aggregation-induced quenching of fluorescence of gold nanoclusters by iodine. The turn-on response of Cys/Hcy shows two linear ranges from 0.0057 to 5 µM and from 8 to 25 µM, with a limit of detection of 9 nM for cysteine and 12 nM for homocysteine. Real samples were analyzed to monitor Cys/Hcy added to human serum. The fluorescence turn-on response of the probe on a paper strip in the presence of Cys/Hcy was studied. Graphical abstract ᅟ.

Fluorometric determination of morphine via its effect on the quenching of fluorescein by gold nanoparticles through a surface energy transfer process.

A method is described for sensitive and selective fluorometric determination of morphine. It is based on the effect of morphine on quenching of the fluorescence of fluorescein by gold nanoparticles (AuNPs) via surface energy transfer. When fluorescein is added to solutions of colloidal AuNPs, its fluorescence becomes quenched due to nanometal surface energy transfer (NSET) because the absorption of AuNPs strongly overlaps the emission spectrum of fluorescein. In the presence of morphine, which contains both a tertiary nitrogen ring atom and a phenolic hydroxy group, it will coordinate to the AuNPs, and this causes recovery of fluorescence. The presence of a tertiary nitrogen ring atom and a phenolic hydroxy group (both required for the effect to occur) in morphine make the probe highly selective and sensitive for morphine. A paper strip assay also was developed by utilizing this detection scheme. The turn-on fluorescent probe was successfully applied to the determination of morphine in spiked serum and urine samples. The method has a 53 pM limit of detection. The paper strip was applied to the determination of morphine in sweat, urine and other biological fluids. It is perceived to be useful for early detection of drug abuse by adolescent. Graphical abstract Schematic of the mechanism of fluorescence turn on detection of morphine using Au NPs (gold nanoparticles) acting asquencher of the fluorescence of fluorescein.

Immature sleep pattern in newborn rats when dams encountered sleep restriction during pregnancy.

There is a growing realization that proper sleep during pregnancy is essential for the health of the mother and the offspring. However, there are no reports on the effects of maternal sleep restriction on the sleep-wake profiles of newborns. So, this study was conducted to evaluate the effects of sleep restriction during the third term of pregnancy on the sleep-wake profiles of neonates born to them. The female pregnant Wistar rats were sleep restricted for 5 h/day on gestational days 15-20 by gentle handling. Sleep-wake profiles of the pups born to them and to the control rats were recorded on postnatal days 1-21. Pups of sleep restricted dams had higher active sleep (AS) and lower quiet sleep (QS) as well as wakefulness. Higher ratio of AS to QS, longer duration of sleep cycles, lesser bout frequency and reduced EEG delta power were also observed in these pups, all of which indicated brain immaturity. All these signs of delayed maturation, usually found in premature babies, were observed in the pups of sleep restricted mothers, who had longer gestation period. This report not only shows the importance of sleep during pregnancy, but it also suggests that neonatal sleep monitoring can be used as a tool for early assessment of retarded brain development.

The effects of rapid eye movement sleep deprivation during late pregnancy on newborns' sleep.

Sleep deprivation during pregnancy is an emerging concern, as it can adversely affect the development of the offspring brain. This study was conducted to evaluate the effects of deprivation of rapid eye movement (REM) sleep during the third term of pregnancy on the sleep-wake profiles of neonates in the Wistar rat model. Sleep-wake patterns were assessed through electrophysiological measures and behavioural observations during postnatal days 1-21 on pups born to REM sleep-deprived dams and control rats. Pups of REM sleep-deprived dams had active sleep that was not only markedly higher in percentage during all the days studied, but also had reduced latency during later postnatal days 15-21. Quiet sleep and wake periods were lower. These factors, along with less frequent but longer sleep-wake cycles, indicated maturational delay in the sleep-wake neural networks. The disruption of time-bound growth of sleep-wake neural networks was substantiated further by the decreased slope of survival plots in the sleep bouts. Examination of altered sleep-wake patterns during early development may provide crucial information concerning deranged neural development in the offspring. This is the first report, to our knowledge, to show that maternal sleep deprivation during pregnancy can delay and impair the development of sleep-wake profile in the offspring.

S,N-doped carbon dots as a fluorescent probe for bilirubin.

Carbon dots doped with sulfur and nitrogen (S,N-CDs) were utilised to design a paper-stripe based fluorescent probe for the detection of bilirubin. The S,N-CDs were synthesized through a microwave assisted route by using citric acid as carbon source and L-cysteine as a source of nitrogen and sulfur. The S,N-CDs exhibit bright blue fluorescence emission with a peak at 452 nm. Fluorescence is quenched by Fe(III) but selectively restored by bilirubin. The quenched fluorescent probe exhibit significant selectivity and sensitivity for bilirubin in the 0.2 nM to 2 nM concentration range, with a 0.12 nM detection limit. The method was applied to the determination of bilirubin in spiked human serum and urine samples. The method was used to design a paper based test stripe as a point of care device for visual bilirubin detection. Graphical abstract Schematic representation of sulphur and nitrogen doped carbon dots whose fluorescence is quenched by Fe(III) and turned on by bilirubin. Photograph of the corresponding system under day light and UV shows the feasibility of the phenomenon. The applicability of the assay was further extended by impregnating the probe on a filter paper.

Dynamic changes in sleep pattern during post-partum in normal pregnancy in rat model.

To develop an animal model for studies on peri-partum sleep disorders, sleep patterns in female Wistar rats during pregnancy, post-partum and after weaning, were assessed and associated adaptive changes in their anxiety were examined. Adult nulliparous female rats, maintained in standard laboratory conditions with ad libitum food and water, were surgically implanted with electroencephalogram and electromyogram electrodes under anaesthesia for objective assessment of sleep-wakefulness (S-W). After post-surgical recovery, three control recordings of S-W were taken for 24h before the animals were kept for mating. After confirmation of pregnancy, S-W recordings were acquired during different days of pregnancy, post-partum lactation/nursing days, and also after weaning. Their anxiety levels were tested in the elevated plus maze. During pregnancy, sleep increased primarily due to increase in light non-REM sleep during dark period. There was an increase in non-REM sleep delta power after parturition, though the sleep was fragmented, especially during daytime. Simultaneous behavioural recording showed increased anxiety during third trimester of pregnancy and gradual reversal of it after parturition. This is the first report where diurnal and nocturnal variations in S-W and delta power, along with adaptive changes in anxiety, were studied before, during and after pregnancy. This study also provides an animal model for drug trials and studies on sleep disorders during peri-partum window.

Sleep deprivation during late pregnancy produces hyperactivity and increased risk-taking behavior in offspring.

Sleep deprivation in women resulting from their modern lifestyle, especially during pregnancy, is a serious concern as it can affect the health of the newborn. Anxiety disorders and cognitive deficits in the offspring are also on the rise. However, experimental studies on the effects of sleep loss during pregnancy, on emotional development and cognitive function of the newborn, are scanty in literature. In the current study, female rats were sleep-deprived for 5h by gentle handling, during the 6 days of the third trimester (days 14-19 of pregnancy). The effects of this sleep deprivation on anxiety-related behaviors of pups during their peri-adolescence age were studied using elevated plus maze (EPM). In addition to body weights of dams and offspring, the maternal behavior was also monitored. The weanlings of sleep-deprived dams showed heightened risk-taking behavior as they made increased explorations into the open arms of EPM. They also showed higher mobility in comparison to the control group. Though the body weights of sleep-deprived dams were comparable to those of the control group, their newborns had lower birth weight. Nevertheless, these pups gained weight and reached the control group values during the initial post-natal week. But after weaning, their rate of growth was lower than that of the control group. This is the first report providing evidences for the role of sleep during late pregnancy in shaping the neuropsychological development in offspring.