Tomas Deierborg

Lund University | LU · Biomedical Center

Dietary patterns that include an excess of foods rich in saturated fat are associated with brain dysfunction. Although microgliosis has been proposed to play a key role in the development of brain dysfunction in diet-induced obesity (DIO), neuroinflammation with cytokine over-expression is often not always observed. Thus, mechanisms by which microg...

Aims According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α‐synuclein (α‐syn) in the gastrointestinal t...

Introduction Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficaci...

INTRODUCTION Neuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin‐3 (Gal‐3), a microglial activation regulator, holds promise as a therapeutic target and potential biomarker. Our study aimed to investigate Gal‐3 levels in patients with FTD and assess its diagnostic potential. METHODS We examined Ga...

Our diets greatly influence our health. Multiple lines of research highlight the beneficial properties of eating berries and fruits. In this study, a berry mixture of Nordic berries previously identified as having the potential to improve memory was supplemented to young C57Bl/6J male mice to investigate effects on cognition function, metabolic hea...

Microglia have an innate immunity memory (IIM) with divergent functions in different animal models of neurodegenerative diseases, including Alzheimer’s disease (AD). AD is characterized by chronic neuroinflammation, neurodegeneration, tau tangles and β-amyloid (Aβ) deposition. Systemic inflammation has been implicated in contributing to the progres...

Alzheimer’s disease (AD) is the most common neurodegenerative disease. Most cases of AD are considered idiopathic and likely due to a combination of genetic, environmental, and lifestyle-related risk factors. Despite occurring decades before the typical age of an AD diagnosis, early-life stress (ELS) has been suggested to have long-lasting effects...

Parkinson’s Disease (PD) is a neurodegenerative and progressive disorder characterised by intracytoplasmic inclusions called Lewy bodies (LB) and degeneration of dopaminergic neurons in the substantia nigra (SN). Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins an...

Microglial cells are brain-specific macrophages that swiftly react to disruptive events in the brain. Microglial activation leads to specific modifications, including proliferation, morphological changes, migration to the site of insult, and changes in gene expression profiles. A change in inflammatory status has been linked to many neurodegenerati...

Background Alzheimer’s disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation is central to the pathology progression, with evidence suggesting that microglia-released galectin-3 (gal3) plays a pivotal role by amplifying neuroinflammation in AD. However, the possible...

Background Physical activity has been proposed to be beneficial for the symptomatic control of bipolar disorder, but the duration of the effects, sex-specific mechanisms, and impact of exercise intensity are not known. Method With an observational study design, we followed skiers and age and sex-matched non-skiers from the general population to in...

Obesity and metabolic syndrome are associated to brain dysfunction, and saturated fat has been suggested to trigger neuroinflammation, including microglia activation, and contribute to neurodegeneration. However, proposed mechanisms of microgliosis and neuroinflammation in obesity are controversial, and might not involve the typical overexpression...

ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β pla...

Galectin-3 (Gal-3) is a beta-galactosidase binding protein involved in microglial activation in the central nervous system (CNS). We previously demonstrated the crucial deleterious role of Gal-3 in microglial activation in Alzheimer’s disease (AD). Under AD conditions, Gal-3 is primarily expressed by microglial cells clustered around Aβ plaques in...

Alzheimer’s disease (AD) is increasingly seen as a disease of synapses and diverse evidence has implicated the amyloid-β peptide (Aβ) in synapse damage. The molecular and cellular mechanism(s) by which Aβ and/or its precursor protein, the amyloid precursor protein (APP) can affect synapses remains unclear. Interestingly, early hyperexcitability has...

The advent of high-throughput single-cell transcriptomic analysis of microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature of some of these activated phenotypes is the upregulation of galectin-3. Representative examples of these phenotypes include disease-associated microglia (DAM) and...

Background The risk of developing Alzheimer’s disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as p...

Light microscopy has been a favorite tool of biological studies for almost a century, recently producing detailed images with exquisite molecular specificity achieving spatial resolution at nanoscale. However, light microscopy is insufficient to provide chemical information as a standalone technique. An increasing amount of evidence demonstrates th...

Background: The tissue damage following a focal stroke causes an inflammatory response that is thought to aggravate the disease state. Galectin-3 is a proinflammatory molecule that has been shown to play a significant role in the inflammatory responses in brain diseases and following experimental stroke. In most animal experiments, young animals a...

According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) starts in the enteric nervous system (ENS) to spread the brain via the vagus nerve. Thus, we were wondering whether human inflammatory bowel diseases (IBD) can progress with appearance of pathogenic alpha-synuclein (alpha-syn) in the gastrointestinal tract and midbrain d...

The proper function of the nervous system is dependent on the appropriate timing of neuronal firing. Synapses continually undergo rapid activity-dependent modifications that require feedback mechanisms to maintain network activity within a window in which communication is energy efficient and meaningful. Homeostatic synaptic plasticity (HSP) and ho...

Background: Alzheimer’s disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation is central to the pathology progression, with evidence suggesting that microglia-released galectin 3 (gal3) plays a pivotal role by amplifying neuroinflammation in AD. However, possible inv...

The amyloid-beta peptide (Aβ) is thought to have prion-like properties promoting its spread throughout the brain in Alzheimer’s disease (AD). However, the cellular mechanism(s) of this spread remains unclear. Here, we show an important role of intracellular Aβ in its prion-like spread. We demonstrate that an intracellular source of Aβ can induce am...

Alzheimer’s disease (AD) accounts for about 70% of neurodegenerative diseases and is a cause of cognitive decline and death for one-third of seniors. AD is currently underdiagnosed, and it cannot be effectively prevented. Aggregation of amyloid-β (Aβ) proteins has been linked to the development of AD, and it has been established that, under patholo...

Physical activity may prevent anxiety, but the importance of exercise intensity, sex-specific mechanisms, and duration of the effects remains largely unknown. We used an observational study design to follow 395,369 individuals for up to 21 years to investigate if participation in an ultralong-distance cross-country ski race (Vasaloppet, up to 90 km...

Alzheimer’s disease (AD) is the most common cause of dementia, costing about 1% of the global economy. Failures of clinical trials targeting amyloid-β protein (Aβ), a key trigger of AD, have been explained by drug inefficiency regardless of the mechanisms of amyloid neurotoxicity, which are very difficult to address by available technologies. Here,...

Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown....

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the globe causing coronavirus disease 2019 (COVID-19). Because it affects the respiratory system, common symptoms are cough and breathing difficulties with fever and fatigue. In addition, some cases progress to acute respiratory distress syndrome (ARDS). The acute ph...

Microglial cells are affected in Alzheimer’s disease (AD) and interact with amyloid-beta (Aβ) plaques. Apart from memory loss, depression is common in patients with AD. Electroconvulsive therapy (ECT) is an anti-depressive treatment that may stimulate microglia, induce neuroinflammation and alter the levels of soluble Aβ, but the effects of ECT on...

Background The exchange of cerebrospinal (CSF) and interstitial fluid is believed to be vital for waste clearance in the brain. The sleep-dependent glymphatic system, which is comprised of perivascular flow of CSF and is largely dependent on arterial pulsatility and astrocytic aquaporin-4 (AQP4) expression, facilitates much of this brain clearance....

Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow-derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in a...

Background: Targeted temperature management (TTM) of 32 to 34 °C has been the standard treatment for out-of-hospital cardiac arrest since clinical trials in 2002 indicated benefit on survival and neurological outcome. In 2013, a clinical trial showed no difference in outcome between TTM of 33 °C and TTM of 36 °C. In this meta-analysis, we investig...

Background Abnormal folding, aggregation and spreading of alpha-synuclein (αsyn) is a mechanistic hypothesis for the progressive neuropathology in Parkinson's disease (PD). Spread of αsyn between cells is supported by clinical, neuropathological and experimental evidence. It has been proposed that a pro-inflammatory micro-environment in response to...

Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junction diseases, and muscle disea...

Early life adversities during childhood (such as maltreatment, abuse, neglect, or parental deprivation) may increase the vulnerability to cognitive disturbances and emotional disorders in both, adolescence and adulthood. Maternal separation (MS) is a widely used model to study stress-related changes in brain and behavior in rodents. In this study,...

COVID-19 disease have become so far the most important sanitary crisis in the XXI century. In light of the events, any clinical resource should be considered to alleviate this crisis. Severe COVID-19 cases present a so-called cytokine storm as the most life-threatening symptom accompanied by lung fibrosis. Galectin-3 has been widely described as re...

Physical exercise has been suggested to reduce the risk of developing Alzheimer’s disease (AD) as well as ameliorate the progression of the disease. However, we recently published results from two large epidemiological studies showing no such beneficial effects on the development of AD. In addition, long-term, voluntary running in the 5xFAD mouse m...

Background: Epilepsy patients commonly exercise less than the general population. Animal studies indicate beneficial effects of physical activity in established epilepsy, while its effect on the development is currently less known. Methods: Here, we investigated the incidence of epilepsy during 20 years in a cohort of participants from the long-...

Objectives: To investigate dogs with acute onset of intracranial signs suspected of stroke by primary veterinary clinicians, and establish possible differential diagnoses and long-term outcome. In addition, serum C-reactive protein and plasma cytokines were investigated as potential biomarkers of disease. Materials and methods: All cases were ev...

Background: Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer's disease (AD) differently in two large study popu...

Background: Physical activity is associated with reduced risk of Parkinson's disease (PD). The explanations for this association are not completely elucidated. We use long-term PD-incidence data from long-distance skiers to study the relationship between exercise and PD. Objective: We aimed to investigate if physical activity is associated with...

Physical activity has been proposed to be beneficial for prevention of depression, although the importance of exercise intensity, sex-specific mechanisms, and duration of the effects need to be clarified. Using an observational study design, following 395,369 individuals up to 21 years we studied whether participation in an ultralong-distance cross...

The glutamate transporter 1 (GLT1) is upregulated during astrocyte development and maturation in vivo and is vital for astrocyte function. Yet it is expressed at low levels by most cultured astrocytes. We previously showed that maturation of human and mouse stem cell-derived astrocytes – including functional glutamate uptake – could be enhanced by...

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate h...

Microglia represent a specialized population of macrophages-like cells in the central nervous system (CNS) considered immune sentinels that are capable of orchestrating a potent inflammatory response. Microglia are also involved in synaptic organization, trophic neuronal support during development, phagocytosis of apoptotic cells in the developing...

Alzheimer's disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta peptide, intraneuronal tau neurofibrillary tangles and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here...

The oral antidiabetic drug metformin is known to exhibit anti-inflammatory properties through activation of AMP kinase, thus protecting various brain tissues as cortical neurons, for example. However, the effect of metformin on the substantia nigra (SN), the main structure affected in Parkinson’s disease (PD), has not yet been studied in depth. Inf...

Effect of metformin on Iba-1, IKKβ and arginase immunostaining in the SN after saline solution (A–C,G–I) and SalMetf (D–F,J–L) treatments. Iba-1 immunofluorescence in (A,D), and IKKβ immunofluorescence in (B,E), show a scarce induction of IKKβ in Iba-1-labeled microglial cells (merge, C,F). Arginase (H,K) is not induced in Iba-1-labeled microglial...

Photographs showing raw bands of IL-1b and GAPDH for the different treatments assayed (three independent experiments in each case). Treatments to BV2 cells: 1, none (control); 2, LPS; 3, LPS + metformin; 4, ATP; 5, LPS + ATP; 6, LPS + ATP + metformin; 7, Metformin; 8, Metformin + ATP.

Photographs showing raw bands of GAPDH, JNK, P-JNK, p38, and P-p38 for the different treatments assayed (four independent experiments in each case). Sal, animals injected with saline solution in the SN plus oral administration of water; SalMetf, animals injected with saline solution in the SN plus oral administration of metformin; LPS, animals inje...

Effect of metformin and LPS on Iba-1, IKKβ and arginase immunostaining in the SN after LPS (A–C,G–I) and LPSMetf (D–F,J–L) treatments. Iba-1 immunofluorescence in (A,D), and IKKβ immunofluorescence in (B,E) show an induction of IKKβ in Iba-1-labeled microglial cells (merge C,F). Arginase (H,K) is not induced in Iba-1-labeled microglial cells, excep...

Photographs showing raw bands of IL-1b and GAPDH for the different treatments assayed (four independent experiments in each case). Treatments to BV2 cells: 1, none (control); 2, LPS; 3, ATP; 4, metformin; 5, LPS + metformin; 6, ATP + metformin; 7, LPS + ATP; 8, LPS + ATP + metformin.

Photographs showing raw bands of JNK, P-JNK, and GAPDH for the different treatments assayed (four independent experiments in each case). Treatments: 1 and 5, Sal, animals injected with saline solution in the SN plus oral administration of water; 2 and 6, SalMetf, animals injected with saline solution in the SN plus oral administration of metformin;...

The oral antidiabetic drug metformin is known to exhibit anti-inflammatory properties through activation of AMP kinase, thus protecting various brain tissues as cortical neurons, for example. However, the effect of metformin on the substantia nigra (SN), the main structure affected in Parkinson's disease (PD), has not yet been studied in depth. Inf...

Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult to the CNS homeostasis. Although microglia have long been recognized as a crucial player in generating and maintaining inflammatory responses in the CNS, now it has become clear, that their function are much more...

Background and Purpose— In ischemic stroke, breakdown of the blood-brain barrier (BBB) aggravates brain damage. Pericyte detachment contributes to BBB disruption and neurovascular dysfunction, but little is known about its regulation in stroke. Here, we investigated how loss of RGS5 (regulator of G protein signaling 5) in pericytes affects BBB brea...

Background: Activated microglia play an essential role in inflammatory responses elicited in the central nervous system (CNS). Microglia-derived extracellular vesicles (EVs) are suggested to be involved in propagation of inflammatory signals and in the modulation of cell-to-cell communication. However, there is a lack of knowledge on the regulation...

Reduced blood flow to the brain induces cerebral ischaemia, potentially causing central injury and peripheral complications including gastrointestinal (GI) dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy in the enteric nervous system (ENS), which is essential in regulating GI function. This study investigates if en...

Alzheimer's disease (AD) is the most common form of dementia characterized by the formation of amyloid plaques (Aβ). Over the last decade, the important role of the innate immune system for the disease development has been established. Chronic activation of microglial cells creates a proinflammatory environment, which is believed to be central for...

Background Oxidative stress and inflammation exacerbate tissue damage in the brain after ischemic stroke. Dimethyl- fumarate (DMF) and its metabolite monomethyl-fumarate (MMF) are known to stimulate anti-oxidant pathways and modulate inflammatory responses. Considering these dual effects of fumarates, we examined the effect of MMF treatment after i...

A large number of human diseases are caused by chronic tissue injury with fibrosis potentially leading to organ failure. There is a need for more effective anti-fibrotic therapies. Congenital muscular dystrophy type 1A (MDC1A) is a devastating form of muscular dystrophy caused by laminin α2 chain-deficiency. It is characterized with early inflammat...

Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galec...

Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galec...

Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response....

In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show tha...

Background Disease progression in retinal neurodegeneration is strongly correlated to immune cell activation, which may have either a neuroprotective or neurotoxic effect. Increased knowledge about the immune response profile and retinal neurodegeneration may lead to candidate targets for treatments. Therefore, we have used the explanted retina as...

Physical exercise is known to be a beneficial factor by increasing the cellular stress tolerance. In ischemic stroke, physical exercise is suggested to both limit the brain injury and facilitate behavioral recovery. In this study we investigated the effect of physical exercise on brain damage following global cerebral ischemia in mice. We aimed to...

Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderl...