A5091820289- Epigenetics and DNA Methylation
- Hemispheric Asymmetry in Neuroscience
- Spinal Cord Injury Research
- Neuroscience of respiration and sleep
- Neuropeptides and Animal Physiology
- Traumatic Brain Injury Research
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Migraine and Headache Studies
- Neuroendocrine regulation and behavior
- Functional Brain Connectivity Studies
- Genetic Syndromes and Imprinting
- Transcranial Magnetic Stimulation Studies
- Neurological disorders and treatments
- Neuroscience and Neuropharmacology Research
- SARS-CoV-2 and COVID-19 Research
- Biochemical effects in animals
- EEG and Brain-Computer Interfaces
- COVID-19 Clinical Research Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Neuroinflammation and Neurodegeneration Mechanisms
- Pain Mechanisms and Treatments
- Identity, Memory, and Therapy
- Alzheimer's disease research and treatments
- Genetics and Physical Performance
Science for Life Laboratory
2022-2025
Uppsala University
2015-2025
Financial University
2011
ABSTRACT The endogenous opioid system (EOS) plays a critical role in addictive processes. Molecular dysregulations this may be specific for different stages of addiction cycle and neurocircuitries involved therefore differentially contribute to the initiation maintenance addiction. Here we evaluated whether EOS is altered brain areas cognitive control including dorsolateral prefrontal cortex (dl‐PFC), orbitofrontal (OFC) hippocampus human alcohol‐dependent subjects. Levels mRNAs were...
Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied field cancerization in BLCA using multi-sample- multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations loss chromosome Y (LOY). analysed 277 samples histologically normal urothelium, 145 tumors 63 blood from 52 males 15 females, in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows...
Abstract Alzheimer’s disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of chromosome Y (LOY) in leukocytes strongly associated with AD. We studied here DNA methylation RNA expression sorted monocytes granulocytes without LOY from male AD patients. Through multi-omic analysis, we identified new candidate genes along those previously Global analyses samples vs. normal state showed that hypomethylation dominated both monocytes. Our...
Traumatic brain injury (TBI) is an established risk factor for neurodegenerative disorders and dementias. Epigenetic modifications, such as DNA methylation, may alter the expression of genes without altering sequence in response to environmental factors. We hypothesized that methylation changes occur injured human be implicated aftermath TBI. The status related neurodegeneration; example, amyloid beta precursor protein (APP), microtubule associated tau (MAPT), neurofilament heavy (NEFH),...
Abstract Background The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows largely unexplained male bias for the severity mortality of disease. Loss chromosome Y (LOY) is risk factor candidate in due to its prior association with many chronic age-related diseases, on immune gene transcription. Methods Publicly available scRNA-seq data PBMC samples derived from patients critically ill were reanalyzed, LOY status was added annotated cells. We further studied...
Molecular changes induced by excessive alcohol consumption may underlie formation of dysphoric state during acute and protracted withdrawal which leads to craving relapse. A main molecular addiction hypothesis is that the upregulation dynorphin (DYN)/κ-opioid receptor (KOR) system in nucleus accumbens (NAc) alcohol-dependent individuals causes imbalance activity D1- D2 dopamine (DR) expressing neural circuits results dysphoria. We here analyzed post-mortem NAc samples human alcoholics assess...
The endogenous opioid peptides dynorphins and enkephalins may be involved in brain-area specific synaptic adaptations relevant for different stages of an addiction cycle. We compared the levels prodynorphin (PDYN) proenkephalin (PENK) mRNAs (by qRT-PCR), radioimmunoassay) caudate nucleus putamen between alcoholics control subjects. also evaluated whether PDYN promoter variant rs1997794 associated with alcoholism affects expression. Postmortem specimens obtained from 24 26 controls were...
ABSTRACT Alzheimer’s disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of chromosome Y (LOY) in leukocytes strongly associated with AD. We studied here DNA methylation RNA expression sorted monocytes granulocytes without LOY from male AD patients. Through multi-omic analysis, we identified new candidate genes confirmed involvement numerous previously Our findings highlight LOY-related differences that occur gene regulatory regions...
Regulation of the formation and rewiring neural circuits by neuropeptides may require coordinated production these signaling molecules their receptors that be established at transcriptional level. Here, we address this hypothesis comparing absolute expression levels opioid peptides with receptors, largest neuropeptide family, characterizing coexpression (transcriptionally coordinated) patterns genes. We demonstrated genes highly correlate within across functionally anatomically different...
Abstract Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke traumatic brain injury remain poorly understood. In early animal studies, a unilateral lesion the cerebellum produced postural asymmetry with ipsilateral hindlimb flexion that was retained after complete spinal cord transection. Here we demonstrate in rats is induced by sensorimotor cortex, characterize this phenomenon as model neuroplasticity underlying asymmetric deficits. After cortical lesion,...
Abstract Unilateral traumatic brain injury and stroke result in asymmetric postural motor deficits including contralateral hemiplegia hemiparesis. In animals, a localized unilateral recapitulates the human upper neuron syndrome formation of hindlimb asymmetry with contralesional limb flexion nociceptive withdrawal reflexes. The current view is that these effects are developed due to aberrant activity pathways descend from into spinal cord. These their target circuits may be regulated by...
Brain injuries can interrupt descending neural pathways that convey motor commands from the cortex to spinal motoneurons. Here, we demonstrate a unilateral injury of hindlimb sensorimotor rats with completely transected thoracic cord produces postural asymmetry contralateral flexion and asymmetric withdrawal reflexes within 3 hr, as well in gene expression patterns lumbar cord. The injury-induced effects were abolished by hypophysectomy mimicked transfusion serum animals brain injury....
Abstract Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss control over intake addictive substances alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced learning memory, while KOR antagonists block excessive, compulsive-like drug alcohol self-administration animal models. In human brain, the DYN/KOR system undergo adaptive changes, along with neuronal...
Neuropeptides are implicated in control of lateralized processes the brain. A unilateral brain injury (UBI) causes contralesional sensorimotor deficits. To examine whether opioid neuropeptides mediate UBI induced asymmetric we compared effects antagonists on and ipsilesional hindlimb responses to left-sided right-sided rats. postural asymmetry (HL-PA) with flexion, activated withdrawal reflex extensor digitorum longus (EDL) evoked by electrical stimulation recorded EMG technique. No...
Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression substance dependence. We here demonstrated PDYN is expressed in neurons human dorsolateral prefrontal cortex (dlPFC), identified neuronal differentially methylated region locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG...
ABSTRACT Alzheimer’s disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of Y (LOY) in leukocytes more prevalent AD patients. We studied DNA methylation, gene expression other epigenetic changes monocytes granulocytes with without LOY from male patients controls. New candidate genes were identified numerous already implicated pathogenesis confirmed. show that multi-omics can define we strengthen role development. The LOY-associated...
Abstract Traumatic brain injury and stroke result in hemiplegia, hemiparesis, asymmetry posture. The effects are mostly contralateral; however, ipsilesional deficits may also develop. We here examined whether ablation controlled cortical impact (CCI), a rat model of clinical focal traumatic injury, both centered over the left or right sensorimotor cortex, induced hindlimb postural (HL-PA) with contralesional limb flexion. was flexed after side injury. In contrast, CCI unexpectedly produced...
Abstract Effects of environmental factors may be transmitted to the following generation, and cause neuropsychiatric disorders including depression, anxiety, posttraumatic stress disorder in offspring. Enhanced synaptic plasticity induced by enrichment also transmitted. We here test hypothesis that effects brain injury pregnant animals produce neurological deficits Unilateral (UBI) ablation hindlimb sensorimotor cortex rats resulted development postural asymmetry (HL‐PA), impairment balance...
ABSTRACT DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies small sample sizes have revealed associations between blood methylation neuropsychopathology, however, large-scale epigenome-wide association (EWAS) are needed investigate the utility profiling peripheral marker for brain....