scholarly journals The Effect of Chronic Morphine or Methadone Exposure and Withdrawal on Clock Gene Expression in the Rat Suprachiasmatic Nucleus and AA-NAT Activity in the Pineal Gland

2016 ◽  
pp. 517-525 ◽  
Author(s):  
D. PAČESOVÁ ◽  
J. NOVOTNÝ ◽  
Z. BENDOVÁ
Keyword(s):  
Pineal Gland ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Brain Structures ◽  
Long Term Effects ◽  
Chronic Morphine ◽  
Clock Gene Expression ◽  
Induced Changes ◽  
Opiate Administration

The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine.

scholarly journals Circadian Clock Genes and Photoperiodism: Comprehensive Analysis of Clock Gene Expression in the Mediobasal Hypothalamus, the Suprachiasmatic Nucleus, and the Pineal Gland of Japanese Quail under Various Light Schedules

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3742-3748 ◽  
Author(s):  
Shinobu Yasuo ◽  
Miwa Watanabe ◽  
Naritoshi Okabayashi ◽  
Shizufumi Ebihara ◽  
Takashi Yoshimura
Keyword(s):  
Pineal Gland ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Expression Patterns ◽  
Hypothalamic Nucleus ◽  
Mediobasal Hypothalamus ◽  
Clock Gene Expression ◽  
Circadian Clock Genes ◽  
Important Center

Abstract In birds, the mediobasal hypothalamus (MBH) including the infundibular nucleus, inferior hypothalamic nucleus, and median eminence is considered to be an important center that controls the photoperiodic time measurement. Here we show expression patterns of circadian clock genes in the MBH, putative suprachiasmatic nucleus (SCN), and pineal gland, which constitute the circadian pacemaker under various light schedules. Although expression patterns of clock genes were different between long and short photoperiod in the SCN and pineal gland, the results were not consistent with those under night interruption schedule, which causes testicular growth. These results indicate that different expression patterns of the circadian clock genes in the SCN and pineal gland are not an absolute requirement for encoding and decoding of seasonal information. In contrast, expression patterns of clock genes in the MBH were stable under various light conditions, which enables animals to keep a steady-state photoinducible phase.

scholarly journals First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Eva Matt ◽  
Lisa Kaindl ◽  
Saskia Tenk ◽  
Anicca Egger ◽  
Teodora Kolarova ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Stimulation ◽  
Longitudinal Design ◽  
Brain Structures ◽  
Brain Network ◽  
Long Term Effects ◽  
Sensorimotor Network ◽  
Functional Brain Network ◽  
Pulse Stimulation

Abstract Background With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior. Methods Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed. Results Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area. Conclusions TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

scholarly journals Trastuzumab in the Treatment of Pregnant Breast Cancer Patients – an Overview of the Literature

2019 ◽  
Vol 79 (06) ◽  
pp. 618-625 ◽  
Author(s):  
Sophia S. Goller ◽  
Udo R. Markert ◽  
Karolin Fröhlich
Keyword(s):  
Breast Cancer ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Long Term Effects ◽  
The Future ◽  
Systemic Adjuvant Therapy ◽  
Induced Changes ◽  
Available Information ◽  
Target Agent

AbstractBreast cancer is one of the most common malignancies which appear during pregnancy. Since women are increasingly not giving birth until they are at a more advanced age, it can be assumed that the incidence of pregnancy-related breast cancers will continue to increase in the future. Because of pregnancy-induced changes and conservative diagnosis, these carcinomas are frequently not detected until they are at an advanced stage and thus generally require systemic adjuvant therapy. The available data on optimal chemotherapeutic management are limited. Particularly for the use of the target agent trastuzumab which could crucially contribute to improving the prognosis in the therapy of HER2-overexpressing breast cancer in non-pregnant women, there is a lack of definitive information regarding the profile of action and safety in pregnancy as well as with regard to any long-term effects on the child. Thirty-eight pregnancies on trastuzumab for the treatment of breast cancer were able to be analysed in the literature currently available. Information can be gained from this and conclusions can be drawn which can individualise and decisively improve therapeutic options in the future for the pregnant breast cancer patient.

scholarly journals Anthracycline-free tumor elimination in mice leads to functional and molecular cardiac recovery from cancer-induced alterations in contrast to long-lasting doxorubicin treatment effects

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Stefan Pietzsch ◽  
Katharina Wohlan ◽  
James T. Thackeray ◽  
Maren Heimerl ◽  
Sven Schuchardt ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Gene Expression Pattern ◽  
Suicide Gene ◽  
Cardiac Response ◽  
Additional Stress ◽  
Repair System ◽  
Long Term Effects ◽  
Recovery Potential

AbstractSystemic effects of advanced cancer impact on the heart leading to cardiac atrophy and functional impairment. Using a murine melanoma cancer model (B16F10 melanoma cells stably transduced with a Ganciclovir (GCV)-inducible suicide gene), the present study analysed the recovery potential of cancer-induced cardiomyopathy with or without use of doxorubicin (Dox). After Dox-free tumor elimination and recovery for 70 ± 5 days, cancer-induced morphologic, functional, metabolic and molecular changes were largely reversible in mice previously bearing tumors. Moreover, grip strength and cardiac response to angiotensin II-induced high blood pressure were comparable with healthy control mice. In turn, addition of Dox (12 mg/kg BW) to melanoma-bearing mice reduced survival in the acute phase compared to GCV-alone induced recovery, while long-term effects on cardiac morphologic and functional recovery were similar. However, Dox treatment was associated with permanent changes in the cardiac gene expression pattern, especially the circadian rhythm pathway associated with the DNA damage repair system. Thus, the heart can recover from cancer-induced damage after chemotherapy-free tumor elimination. In contrast, treatment with the cardiotoxic drug Dox induces, besides well-known adverse acute effects, long-term subclinical changes in the heart, especially of circadian clock genes. Since the circadian clock is known to impact on cardiac repair mechanisms, these changes may render the heart more sensitive to additional stress during lifetime, which, at least in part, could contribute to late cardiac toxicity.

scholarly journals Time-restricted feeding near dawn entrains long-term behavioral changes through the suprachiasmatic nucleus

2021 ◽  
Author(s):  
Qiaocheng Zhai ◽  
Yizhun Zeng ◽  
Yue Gu ◽  
Tao Zhang ◽  
Baoshi Yuan ◽  
...  
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Behavioral Changes ◽  
Gabaergic Neuron ◽  
Receptor Interaction ◽  
Neuron Activity ◽  
Restricted Feeding ◽  
Peripheral Tissues ◽  
After Effect

AbstractThe suprachiasmatic nucleus (SCN) is a master circadian pacemaker known to integrate light intensity and seasonal information with peripheral tissues to coordinate daily rhythms of physiology and behavior. However, the contribution of food information to the regulation of the SCN network remains controversial. Here, we identified the effect induced by time-restricted feeding (TRF) at dawn, but not at another time widow, inducing a robust and long-term shift in locomotor behavior and increased wakefulness. Comparing the oscillations of intracellular Ca2+ signals in the SCN GABAergic neurons of freely moving mice, before and after TRF, revealed significant activation of these neurons in dawn-TRF mice. Moreover, RNA-seq profiling in the dawn TRF-induced behavioral changes identified altered expressed genes involved in regulating extracellular exosome, ion transporters, and ECM-receptor interaction, but not core clock genes. Furthermore, injection in the SCN of insulin-like growth factor (IGF2) inhibitor Chromeceptin, targeting the most upregulated gene in extracellular exosome, abolished the after effect induced by ZT0-4 TRF. Finally, GABAergic-neuron-specific disruption of the potassium-chloride cotransporter Kcc2 intensified the dawn TRF-induced after effect, indicating that Kcc2 encodes food intake derived signals that control SCN clock entrainment. Thus, our study functionally links SCN GABAergic neuron activity and central clock entrainment regulation to both hunger- and food-response-related behaviors in mice.

scholarly journals Long-term demographic consequences of a seed dispersal disruption

2012 ◽  
Vol 279 (1741) ◽  
pp. 3298-3303 ◽  
Author(s):  
Anna Traveset ◽  
Juan P. González-Varo ◽  
Alfredo Valido
Keyword(s):  
Long Term Effects ◽  
Ecological Processes ◽  
Cascading Effects ◽  
Island Populations ◽  
Mutualistic Interaction ◽  
Entire Plant ◽  
Local Extinctions ◽  
Long Term Consequences ◽  
Induced Changes

The loss or decline of vertebrate frugivores can limit the regeneration of plants that depend on them. However, empirical evidence is showing that this is still very scarce, as functionally equivalent species may contribute to maintain the mutualistic interaction. Here, we investigated the long-term consequences of the extinction of frugivorous lizards on the population persistence of a Mediterranean relict shrub Cneorum tricoccon (Cneoraceae). We examined the demographic parameters among 26 insular and mainland populations, which encompass the entire plant distributional range, comparing populations with lizards with those in which these are extinct, but in which alien mammals currently act as seed dispersers. Plant recruitment was found to be higher on island populations with lizards than on those with mammals, and the long-term effects of the native disperser's loss were found in all vital phases of plant regeneration. The study thus gives evidence of the cascading effects of human-induced changes in ecosystems, showing how the disruption of native ecological processes can lead to species regression and, in the long term, even to local extinctions.

scholarly journals Sleep–wake-driven and circadian contributions to daily rhythms in gene expression and chromatin accessibility in the murine cortex

2019 ◽  
Vol 116 (51) ◽  
pp. 25773-25783 ◽  
Author(s):  
Charlotte N. Hor ◽  
Jake Yeung ◽  
Maxime Jan ◽  
Yann Emmenegger ◽  
Jeffrey Hubbard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Serum Response Factor ◽  
Clock Genes ◽  
Chromatin Accessibility ◽  
Long Term Effects ◽  
Homeostatic Process ◽  
Gene Expression Dynamics ◽  
Damped Oscillation

The timing and duration of sleep results from the interaction between a homeostatic sleep–wake-driven process and a periodic circadian process, and involves changes in gene regulation and expression. Unraveling the contributions of both processes and their interaction to transcriptional and epigenomic regulatory dynamics requires sampling over time under conditions of unperturbed and perturbed sleep. We profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a 3-d period, including a 6-h sleep deprivation (SD) on day 2. We used mathematical modeling to integrate time series of mRNA expression data with sleep–wake history, which established that a large proportion of rhythmic genes are governed by the homeostatic process with varying degrees of interaction with the circadian process, sometimes working in opposition. Remarkably, SD caused long-term effects on gene-expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a damped oscillation of most core clock genes, includingArntl/Bmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Dynamics in distal regions, rather than promoters, correlated with mRNA expression, implying that changes in expression result from constitutively accessible promoters under the influence of enhancers or repressors. Serum response factor (SRF) was predicted as a transcriptional regulator driving immediate response, suggesting that SRF activity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level and highlights the importance of the sleep–wake distribution to diurnal rhythmicity and circadian processes.

scholarly journals The Impact of Sports-Related Concussions on the Language System

2018 ◽  
Vol 1 (1) ◽  
pp. 36-46
Author(s):  
Patrick S Ledwidge
Keyword(s):  
Brain Activity ◽  
Brain Regions ◽  
Functional Brain Imaging ◽  
Long Term Effects ◽  
Brain Potentials ◽  
Language System ◽  
Induced Changes ◽  
The Impact ◽  
Language Network

Sports-related Concussions (SRC) and their potential long-term effects are a growing concern among athletes and their families. Research utilizing functional brain imaging/recording techniques (e.g., fMRI, ERP) seeks to explain how neurocognitive brain activity changes in the days and years following SRC. Although language deficits are documented following non-sports related concussion there remains a striking lack of research on how SRCs may influence the language system and their supporting neural mechanisms. Neuroimaging findings, however, demonstrate that SRCs alter structural and functional pathways within the frontotemporal language network. Brain regions included in this network generate language-related event-related brain potentials (ERPs), including the N400 and P600. ERPs have been used to demonstrate long-term neurocognitive alterations associated with concussion and may also provide objective and robust markers of SRC-induced changes to the language system.

scholarly journals Simple and complex interactions between sleep-wake driven and circadian processes shape daily genome regulatory dynamics in the mouse

2019 ◽  
Author(s):  
Charlotte N. Hor ◽  
Jake Yeung ◽  
Maxime Jan ◽  
Yann Emmenegger ◽  
Jeffrey Hubbard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sleep Deprivation ◽  
Mrna Expression ◽  
Clock Genes ◽  
Poor Quality ◽  
Chromatin Accessibility ◽  
Time Of Day ◽  
Long Term Effects ◽  
Regulatory Dynamics

AbstractThe timing and duration of sleep results from the interaction between a sleep-wake driven, or homeostatic, process (S) and a circadian process (C), and involves changes in gene expression and genomic regulation. Unraveling the respective contributions of S and C, and their interaction, to transcriptional and epigenomic regulatory dynamics requires sampling over time under unperturbed conditions and conditions of perturbed sleep. Here, we profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a three-day period, including a 6-hour sleep deprivation (SD) on day two. Mathematical modeling established that a large proportion of rhythmic genes are actually governed by Process S with varying degrees of interaction with Process C, sometimes working in opposition. Remarkably, SD causes long-term effects on gene expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a dampening of the oscillation of most core clock genes, including Bmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Distal regions, rather than promoters, display dynamics corresponding to gene transcription, implying that changes in mRNA expression result from constantly accessible promoters under the influence of distal enhancers or repressors. Srf was predicted as a transcriptional regulator driving immediate response, suggesting that Srf activity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level. Such effects might accumulate with repeated sleep restrictions, thereby contributing to their adverse health effects.Significance statementWhen and how long we sleep is determined by the time-of-day and how long we have been awake, which are tracked molecularly by a circadian and a sleep-wake driven process, respectively. We measured the long-term consequences of a short-term sleep deprivation (SD) on gene expression and regulation in the mouse brain, and used mathematical models to determine the relative contributions of the circadian and sleep-wake driven processes. We find that many genes, including most of the genes that constitute the molecular circadian clock, are perturbed by SD long after the mice ceased showing behavioral signs of sleep loss. Our results have implications for human health, given the high prevalence of insufficient and poor quality sleep in our contemporary society.

scholarly journals Photorefractoriness in Mammals: Dissociating a Seasonal Timer from the Circadian-Based Photoperiod Response

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3782-3790 ◽  
Author(s):  
Gerald A. Lincoln ◽  
Jonathan D. Johnston ◽  
Hakan Andersson ◽  
Gabriela Wagner ◽  
David G. Hazlerigg
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Prolonged Exposure ◽  
Clock Genes ◽  
Photoperiodic Response ◽  
Photoperiod Response ◽  
Pars Tuberalis ◽  
Target Tissue ◽  
Glycoprotein Hormone ◽  
Rhythmic Expression

Abstract In seasonal animals, prolonged exposure to constant photoperiod induces photorefractoriness, causing spontaneous reversion in physiology to that of the previous photoperiodic state. This study tested the hypothesis that the onset of photorefractoriness is correlated with a change in circadian expression of clock genes in the suprachiasmatic nucleus (circadian pacemaker) and the pars tuberalis (PT, a melatonin target tissue). Soay sheep were exposed to summer photoperiod (16-h light) for either 6 or 30 wk to produce a photostimulated and photorefractory physiology, and seasonal changes were tracked by measuring the long-term prolactin cycles. Animals were killed at 4-h intervals throughout 24 h. Contrary to the hypothesis, the 24-h rhythmic expression of clock genes (Rev-erbα, Per1, Per2, Bmal1, Cry1) in the suprachiasmatic nucleus and PT reflected the ambient photoperiod/melatonin signal and not the changing physiology. Contrastingly, the PT expression of α-glycoprotein hormone subunit (αGSU) and βTSH declined in photorefractory animals toward a short day-like endocrinology. We conclude that the generation of long-term endocrine cycles depends on the interaction between a circadian-based, melatonin-dependent timer that drives the initial photoperiodic response and a non-circadian-based timer that drives circannual rhythmicity in long-lived species. Under constant photoperiod the two timers can dissociate, leading to the apparent refractory state.

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