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Turkish Journal of Medical Sciences 2023The cause and treatment of electrical status epilepticus during sleep (ESES), one of the epileptic encephalopathies of childhood, is unclear. The aim of this study was...
BACKGROUND/AIM
The cause and treatment of electrical status epilepticus during sleep (ESES), one of the epileptic encephalopathies of childhood, is unclear. The aim of this study was to evaluate possible microstructural abnormalities in the brain using advanced magnetic resonance imaging (MRI) techniques in ESES patients with and without genetic mutations.
MATERIALS AND METHODS
This research comprised 12 ESES patients without structural thalamic lesions (6 with genetic abnormalities and 6 without) and 12 healthy children. Whole-exome sequencing was used for the genetic mutation analysis. Brain MRI data were evaluated using tractus-based spatial statistics, voxel-based morphometry, a local gyrification index, subcortical shape analysis, FreeSurfer volume, and cortical thickness. The data of the groups were compared.
RESULTS
The mean age in the control group was 9.05 ± 1.85 years, whereas that in the ESES group was 9.45 ± 2.72 years. Compared to the control group, the ESES patients showed higher mean thalamus diffusivity (p < 0.05). ESES patients with genetic mutations had lower axial diffusivity in the superior longitudinal fasciculus and gray matter volume in the entorhinal region, accumbens area, caudate, putamen, cerebral white matter, and outer cerebellar areas. The superior and middle temporal cortical thickness increased in the ESES patients.
CONCLUSION
This study is important in terms of presenting the microstructural evaluation of the brain in ESES patients with advanced MRI analysis methods as well as comparing patients with and without genetic mutations. These findings may be associated with corticostriatal transmission, ictogenesis, epileptogenesis, neuropsychiatric symptoms, cognitive impairment, and cerebellar involvement in ESES. Expanded case-group studies may help to understand the physiology of the corticothalamic circuitry in its etiopathogenesis and develop secondary therapeutic targets for ESES.
Topics: Humans; Status Epilepticus; Male; Child; Female; Magnetic Resonance Imaging; Brain; Sleep; Adolescent; Case-Control Studies; Thalamus
PubMed: 38813507
DOI: 10.55730/1300-0144.5754 -
Frontiers in Endocrinology 2024This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin,... (Review)
Review
This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin, herein referred to as Source #1, is the pineal gland. In this organ, melatonin production is circadian with maximal synthesis and release into the blood and cerebrospinal fluid occurring during the night. Of the total amount of melatonin produced in mammals, we speculate that less than 5% is synthesized by the pineal gland. The melatonin rhythm has the primary function of influencing the circadian clock at the level of the suprachiasmatic nucleus (the CSF melatonin) and the clockwork in all peripheral organs (the blood melatonin) via receptor-mediated actions. A second source of melatonin (Source # 2) is from multiple tissues throughout the body, probably being synthesized in the mitochondria of these cells. This constitutes the bulk of the melatonin produced in mammals and is concerned with metabolic regulation. This review emphasizes the action of melatonin from peripheral sources in determining re-dox homeostasis, but it has other critical metabolic effects as well. Extrapineal melatonin synthesis does not exhibit a circadian rhythm and it is not released into the blood but acts locally in its cell of origin and possibly in a paracrine matter on adjacent cells. The factors that control/influence melatonin synthesis at extrapineal sites are unknown. We propose that the concentration of melatonin in these cells is determined by the subcellular redox state and that melatonin synthesis may be inducible under stressful conditions as in plant cells.
Topics: Melatonin; Humans; Animals; Circadian Rhythm; Pineal Gland; Suprachiasmatic Nucleus
PubMed: 38808108
DOI: 10.3389/fendo.2024.1414463 -
Fluids and Barriers of the CNS May 2024Choroid plexus (ChP), the brain structure primarily responsible for cerebrospinal fluid production, contains a robust circadian clock, whose role remains to be...
Choroid plexus (ChP), the brain structure primarily responsible for cerebrospinal fluid production, contains a robust circadian clock, whose role remains to be elucidated. The aim of our study was to [1] identify rhythmically controlled cellular processes in the mouse ChP and [2] assess the role and nature of signals derived from the master clock in the suprachiasmatic nuclei (SCN) that control ChP rhythms. To accomplish this goal, we used various mouse models (WT, mPer2, ChP-specific Bmal1 knockout) and combined multiple experimental approaches, including surgical lesion of the SCN (SCNx), time-resolved transcriptomics, and single cell luminescence microscopy. In ChP of control (Ctrl) mice collected every 4 h over 2 circadian cycles in darkness, we found that the ChP clock regulates many processes, including the cerebrospinal fluid circadian secretome, precisely times endoplasmic reticulum stress response, and controls genes involved in neurodegenerative diseases (Alzheimer's disease, Huntington's disease, and frontotemporal dementia). In ChP of SCNx mice, the rhythmicity detected in vivo and ex vivo was severely dampened to a comparable extent as in mice with ChP-specific Bmal1 knockout, and the dampened cellular rhythms were restored by daily injections of dexamethasone in mice. Our data demonstrate that the ChP clock controls tissue-specific gene expression and is strongly dependent on the presence of a functional connection with the SCN. The results may contribute to the search for a novel link between ChP clock disruption and impaired brain health.
Topics: Animals; Suprachiasmatic Nucleus; Choroid Plexus; Circadian Clocks; Mice; Mice, Inbred C57BL; Circadian Rhythm; Male; Mice, Knockout; ARNTL Transcription Factors
PubMed: 38802875
DOI: 10.1186/s12987-024-00547-3 -
Molecular Brain May 2024The Hypothalmic-Pituitary-Adrenal axis also known as the HPA axis is central to stress response. It also acts as the relay center between the body and the brain. We...
The Hypothalmic-Pituitary-Adrenal axis also known as the HPA axis is central to stress response. It also acts as the relay center between the body and the brain. We analysed hypothalamic proteome from mice subjected to chronic social defeat paradigm using iTRAQ based quantitative proteomics to identify changes associated with stress response. We identified greater than 2000 proteins after processing our samples analysed through Q-Exactive (Thermo) and Orbitrap Velos (Thermo) at 5% FDR. Analysis of data procured from the runs showed that the proteins whose levels were affected belonged primarily to mitochondrial and metabolic processes, translation, complement pathway among others. We also found increased levels of fibrinogen, myelin basic protein (MBP) and neurofilaments (NEFL, NEFM, NEFH) in the hypothalamus from socially defeated mice. Interestingly, research indicates that these proteins are upregulated in blood and CSF of subjects exposed to trauma and stress. Since hypothalamus secreted proteins can be found in blood and CSF, their utility as biomarkers in depression holds an impressive probability and should be validated in clinical samples.
Topics: Animals; Hypothalamus; Stress, Psychological; Social Defeat; Male; Mice, Inbred C57BL; Proteomics; Mice; Proteome
PubMed: 38802853
DOI: 10.1186/s13041-024-01096-4 -
Nature Communications May 2024Unified visual perception requires integration of bottom-up and top-down inputs in the primary visual cortex (V1), yet the organization of top-down inputs in V1 remains...
Unified visual perception requires integration of bottom-up and top-down inputs in the primary visual cortex (V1), yet the organization of top-down inputs in V1 remains unclear. Here, we used optogenetics-assisted circuit mapping to identify how multiple top-down inputs from higher-order cortical and thalamic areas engage V1 excitatory and inhibitory neurons. Top-down inputs overlap in superficial layers yet segregate in deep layers. Inputs from the medial secondary visual cortex (V2M) and anterior cingulate cortex (ACA) converge on L6 Pyrs, whereas ventrolateral orbitofrontal cortex (ORBvl) and lateral posterior thalamic nucleus (LP) inputs are processed in parallel in Pyr-type-specific subnetworks (Pyr and Pyr) and drive mutual inhibition between them via local interneurons. Our study deepens understanding of the top-down modulation mechanisms of visual processing and establishes that V2M and ACA inputs in L6 employ integrated processing distinct from the parallel processing of LP and ORBvl inputs in L5.
Topics: Animals; Primary Visual Cortex; Optogenetics; Male; Thalamus; Visual Pathways; Neurons; Visual Cortex; Gyrus Cinguli; Interneurons; Visual Perception; Mice; Female; Brain Mapping
PubMed: 38802410
DOI: 10.1038/s41467-024-48924-8 -
Frontiers in Endocrinology 2024Previous studies have revealed the sex-specific features of pituitary-thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and...
Sex-specific associations between the developmental alterations in the pituitary-thyroid hormone axis and thyroid nodules in Chinese euthyroid adults: a community-based cross-sectional study.
BACKGROUND
Previous studies have revealed the sex-specific features of pituitary-thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary-TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQI) and the thyroid feedback quantile-based index by FT3(TFQI) with of TNs in Chinese euthyroid adults.
METHODS
8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted.
RESULTS
TFQI among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQI levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both for trend < 0.05). Additionally, lower TFQI and TFQI levels were significantly associated with a higher prevalence of TNs in women (both for trend < 0.05), and lower TFQI levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQI and TFQI levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQI and the prevalence or number of TNs in men were not found.
CONCLUSIONS
The trends of THs, TSH, TFQI, and TFQI at different ages were sex-dependent. Both TFQI and TFQI levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs.
Topics: Humans; Male; Female; Thyroid Nodule; Adult; Cross-Sectional Studies; Middle Aged; China; Thyroid Hormones; Pituitary Gland; Thyrotropin; Thyroid Gland; Aged; Sex Factors; Young Adult; Prevalence; Sex Characteristics; East Asian People
PubMed: 38800483
DOI: 10.3389/fendo.2024.1379103 -
Addiction Biology May 2024Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health....
Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.
Topics: Humans; Male; Aged; Female; Longitudinal Studies; Brain; White Matter; Aged, 80 and over; Magnetic Resonance Imaging; Gray Matter; Alcohol Drinking; Atrophy; Aging; Binge Drinking; Thalamus; Hippocampus; Amygdala; Corpus Callosum
PubMed: 38797559
DOI: 10.1111/adb.13402 -
Translational Psychiatry May 2024In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic...
In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic dysfunction. Impaired release of oxytocin can lead to cognitive impairment and affect prognosis and long-term quality of life after hypothalamic injury. Hypothalamic injury-induced cognitive dysfunction was detected in male animals. Behavioral parameters were measured to assess the characteristics of cognitive dysfunction induced by hypothalamic-pituitary stalk lesions. Brains were collected for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in hippocampal regions highly associated with cognitive function after injury to corresponding hypothalamic areas. Through transcriptomic analysis, we confirmed the loss of oxytocin neurons after hypothalamic injury and the reversal of hypothalamic-induced cognitive dysfunction after oxytocin supplementation. Furthermore, overactivation of the ERK signaling pathway and β-amyloid deposition in the hippocampal region after hypothalamic injury were observed, and cognitive function was restored after inhibition of ERK signaling pathway overactivation. Our findings suggest that cognitive dysfunction after hypothalamic injury may be caused by ERK hyperphosphorylation in the hippocampal region resulting from a decrease in the number of oxytocin neurons, which in turn causes β-amyloid deposition.
Topics: Oxytocin; Animals; Hippocampus; Male; Cognitive Dysfunction; Hypothalamus; MAP Kinase Signaling System; Amyloid beta-Peptides; Neurons; Disease Models, Animal; Mice; Phosphorylation
PubMed: 38796566
DOI: 10.1038/s41398-024-02930-y -
International Journal of Molecular... May 2024In contrast to the hypothesis that aging results from cell-autonomous deterioration processes, the programmed longevity theory proposes that aging arises from a partial...
In contrast to the hypothesis that aging results from cell-autonomous deterioration processes, the programmed longevity theory proposes that aging arises from a partial inactivation of a "longevity program" aimed at maintaining youthfulness in organisms. Supporting this hypothesis, age-related changes in organisms can be reversed by factors circulating in young blood. Concordantly, the endocrine secretion of exosomal microRNAs (miRNAs) by hypothalamic neural stem cells (htNSCs) regulates the aging rate by enhancing physiological fitness in young animals. However, the specific molecular mechanisms through which hypothalamic-derived miRNAs exert their anti-aging effects remain unexplored. Using experimentally validated miRNA-target gene interactions and single-cell transcriptomic data of brain cells during aging and heterochronic parabiosis, we identify the main pathways controlled by these miRNAs and the cell-type-specific gene networks that are altered due to age-related loss of htNSCs and the subsequent decline in specific miRNA levels in the cerebrospinal fluid (CSF). Our bioinformatics analysis suggests that these miRNAs modulate pathways associated with senescence and cellular stress response, targeting crucial genes such as , , and . The oligodendrocyte lineage appears to be the most responsive to age-dependent loss of exosomal miRNA, leading to significant derepression of several miRNA target genes. Furthermore, heterochronic parabiosis can reverse age-related upregulation of specific miRNA-targeted genes, predominantly in brain endothelial cells, including senescence promoting genes such as and . Our findings support the presence of an anti-senescence mechanism triggered by the endocrine secretion of htNSC-derived exosomal miRNAs, which is associated with a youthful transcriptional signature.
Topics: MicroRNAs; Animals; Exosomes; Hypothalamus; Aging; Neural Stem Cells; Gene Regulatory Networks; Cellular Senescence; Brain; Mice; Parabiosis; Oligodendroglia; Transcriptome; Gene Expression Regulation; Gene Expression Profiling
PubMed: 38791505
DOI: 10.3390/ijms25105467 -
International Journal of Molecular... May 2024Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading to adverse foetal...
Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.
Topics: Animals; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Female; Pregnancy; Prediabetic State; Rats; Adrenocorticotropic Hormone; Rats, Sprague-Dawley; Corticosterone; Male; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Prenatal Exposure Delayed Effects; Diabetes Mellitus, Type 2; Insulin Resistance
PubMed: 38791468
DOI: 10.3390/ijms25105431