Publications by authors named "Regina Vontell"

Article Synopsis
  • Parkinson's Disease (PD) is a serious brain disorder affecting over 1% of people over 60, leading to issues with movement and thinking, but its exact causes are still unclear.
  • To investigate the complexity of PD, researchers conducted single-nucleus RNA sequencing and whole-genome sequencing on 100 postmortem samples, selecting cases that represent varying stages and symptoms of the disease.
  • The resulting dataset, created with high standards of quality control, is freely available on the AMP PD Knowledge Platform, facilitating research into the molecular mechanisms of PD and potentially helping to improve treatment options.
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  • ε4 is the most significant genetic risk factor for Alzheimer's disease (AD), with about half of AD patients having at least one ε4 allele.
  • Researchers found that the African-specific A allele of rs10423769 significantly reduces the AD risk associated with ε4 homozygotes by roughly 75%.
  • The protective variant is located in a specific region of chromosome 19, demonstrating differences at the structural and DNA methylation levels compared to non-protective variants, and emphasizing the need for diverse ancestry representation in AD studies.
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  • The study investigates how cerebral amyloid angiopathy (CAA) affects recovery from ischemic stroke using a 5xFAD mouse model, hypothesizing that amyloid-beta buildup leads to worse outcomes by impairing the blood-brain barrier (BBB).
  • Findings reveal that CAA worsens stroke effects, resulting in narrowed BBB microvessels, decreased cerebral blood flow, and hindered tissue recovery, alongside different gene expression patterns in endothelial cells and neural progenitor cells in the hippocampus.
  • Experiments indicate that disrupting the CXCL12-PIK3C2A-CREB3L2 pathway negatively impacts neurogenesis, but activating the PI3K pathway can restore it
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Dementia is a group of symptoms including memory loss, language difficulties, and other types of cognitive and functional impairments that affects 57 million people worldwide, with the incidence expected to double by 2040. Therefore, there is an unmet need to develop reliable biomarkers to diagnose early brain impairments so that emerging interventions can be applied before brain degeneration. Here, we performed biomarker analyses for apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-β 42/40 (Aβ) ratio in the plasma of older adults.

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Schizophrenia (SCZ) is a complex psychiatric disorder that involves an inflammatory response thought to be characterized by microglial activation. The inflammasome complex may play critical roles in the pathomechanism of neuroinflammation but how this relates to SCZ remains unclear. In this study, we performed an immunohistochemical (IHC) analysis to compare the expression of inflammasome proteins in brain tissue from donors with SCZ (n = 16) and non-psychiatric donors (NP; n = 13) isolated from the superior frontal cortex (SFC), superior temporal cortex, and anterior cingulate cortex brain regions.

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The development of the human central nervous system initiates in the early embryonic period until long after delivery. It has been shown that several neurological and neuropsychiatric diseases originate from prenatal incidents. Mathematical models offer a direct way to understand neurodevelopmental processes better.

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Introduction: Severity and distribution of aggregated tau and neurofibrillary tangles (NFT) are strongly correlated with the clinical presentation of Alzheimer's disease (AD). Clearance of aggregated tau could decrease the rate of NFT formation and delay AD onset. Recent studies implicate corpora amylacea (CA) as a regulator of onset or accumulation of tau pathology.

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Introduction: Neurogranin (Ng) is considered a biomarker for synaptic dysfunction in Alzheimer's disease (AD). In contrast, the inflammasome complex has been shown to exacerbate AD pathology.

Methods: We investigated the protein expression, morphological differences of Ng, and correlated Ng to hyperphosphorylated tau in the brains of 17 AD cases and 17 age- and sex-matched controls.

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Cetaceans are well-regarded as sentinels for toxin exposure. Emerging studies suggest that cetaceans can also develop neuropathological changes associated with neurodegenerative disease. The occurrence of neuropathology makes cetaceans an ideal species for examining the impact of marine toxins on the brain across the lifespan.

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Alzheimer's disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive function. Inflammasome activation has been suggested to play a critical role in the neuroinflammatory response in AD progression, but the cell-type expression of inflammasome proteins in the brain has not been fully characterized. In this study, we used samples from the hippocampus formation, the subiculum, and the entorhinal cortex brain from 17 donors with low-level AD pathology and 17 intermediate AD donors to assess the expression of inflammasome proteins.

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The dynamic geometry of neuronal development is an essential concept in theoretical neuroscience. We aimed to design a mathematical model which outlines stepwise in an innovative form and designed to model neuronal development geometrically and modelling spatially the neuronal-electrical field interaction. We demonstrated flexibility in forming the cell and its nucleus to show neuronal growth from inside to outside that uses a fractal cylinder to generate neurons (pyramidal/sphere) in form of mathematically called 'surface of revolution'.

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Osteopontin (OPN) is a matricellular protein that mediates various physiological functions and is implicated in neuroinflammation, myelination, and perinatal brain injury. However, its expression in association with brain injury in preterm infants is unexplored. Here we examined the expression of OPN in postmortem brains of preterm infants and explored how this expression is affected in brain injury.

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Schizophrenia (SCZ) is a psychiatric disorder that can include symptoms of disorganized speech and thoughts with uncertain underlying mechanisms possibly linked to over-activated microglia. In this study, we used brain samples from sixteen donors with SCZ and thirteen control donors to assess the differential activation of microglia by quantifying density and 3D reconstruction of microglia stained with ionized calcium-binding adaptor molecule-1 (Iba1). Our samples consisted of sections from the frontal, temporal, and cingulate cortical gray matter, subcortical white matter regions (SCWM), and included the anterior corpus callosum.

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Introduction: Synaptic damage is a key pathology of Alzheimer's disease (AD). The mechanism underlying synaptic vulnerability in AD remains elusive.

Methods: Using a large-scale transcriptomic dataset, we analyzed the neurogranin-centered integrative gene network and assessed the correlation of neurogranin () gene expression with AD pathology in brains.

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Down syndrome (DS) occurs with triplication of human chromosome 21 and is associated with deviations in cortical development evidenced by simplified gyral appearance and reduced cortical surface area. Radial glia are neuronal and glial progenitors that also create a scaffolding structure essential for migrating neurons to reach cortical targets and therefore play a critical role in cortical development. The aim of this study was to characterise radial glial expression pattern and morphology in the frontal lobe of the developing human fetal brain with DS and age-matched controls.

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Preterm brain injury, occurring in approximately 30% of infants born <32 weeks gestational age, is associated with an increased risk of neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The mechanism of gray matter injury in preterm born children is unclear and likely to be multifactorial; however, inflammation, a high predictor of poor outcome in preterm infants, has been associated with disrupted interneuron maturation in a number of animal models. Interneurons are important for regulating normal brain development, and disruption in interneuron development, and the downstream effects of this, has been implicated in the etiology of neurodevelopmental disorders.

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Article Synopsis
  • The Cytoplasmic Actin Gamma 1 gene variant is autosomal dominant and associated with central nervous system anomalies, specifically Baraitser Winter Malformation Syndrome (BWMS), which includes conditions like agenesis of the corpus callosum (ACC) and neuronal heterotopia.
  • A neonatal case study highlighted ACC and neuronal heterotopia diagnosed via antenatal MRI showed clusters of neurons in the brain's subcortical and periventricular white matter, with impaired glial formation observed post-mortem.
  • Investigations using immunohistochemistry revealed alterations in neuronal and glial cell distributions in specific brain regions, with notable deficiencies in mid
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Bestrophin-3, a potential candidate for a calcium-activated chloride channel, recently was suggested to have cell-protective functions. We studied the expression and alternative splicing of bestrophin-3 in neonatal mouse brain and after hypoxic-ischemic (HI) injury and in human neonatal brain samples. HI brain injury was induced in 9-day old mice by unilateral permanent common carotid artery occlusion in combination with exposure to 10% oxygen for 50 min.

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Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine member of the TNF family. TWEAK binds to its only known receptor, Fn14, enabling it to activate downstream signaling processes in response to tissue injury. The aim of this study was to investigate the role of TWEAK signaling in neonatal hypoxia-ischemia (HI).

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Background: Periventricular leukomalacia (PVL) is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia-ischemia (HI) and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.

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Background: Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy.

Methods: In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (αβT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd , lacking γδT cells), and TCRα-deficient (Tcra , lacking αβT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2.

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Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurologic disabilities. Inflammation contributes to perinatal brain injury development, but the essential mediators that lead to early-life brain injury remain largely unknown. Neonates have reduced capacity for mounting conventional αβT-cell responses.

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Hypoxia-ischemia (HI) can result in permanent life-long injuries such as motor and cognitive deficits. In response to cellular stressors such as hypoxia, tumor suppressor protein p53 is activated, potently initiating apoptosis and promoting Bax-dependent mitochondrial outer membrane permeabilization. The aim of this study was to investigate the effect of Trp53 genetic inhibition on injury development in the immature brain following HI.

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The cognitive and behavioural deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than TBI in the mature brain. Understanding this developmental sensitivity is critical as children under four years of age sustain TBI more frequently than any other age group. Microglia (MG), resident immune cells of the brain that mediate neuroinflammation, are activated following TBI in the immature brain.

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Apoptotic mechanisms are centre stage for the development of injury in the immature brain, and caspases have been shown to play a pivotal role during brain development and in response to injury. The inhibition of caspases using broad-spectrum agents such as Q-VD-OPh is neuroprotective in the immature brain. Caspase-6, an effector caspase, has been widely researched in neurodevelopmental disorders and found to be important following adult stroke, but its function in the neonatal brain has yet to be detailed.

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