Carlos Matute

• PhD
• University of the Basque Country

Cortical damage and dysfunction is a pathological hallmark of multiple sclerosis (MS) that correlates with the severity of physical and cognitive disability. Astrocytes participate in MS pathobiology through a variety of mechanisms, and abnormal astrocytic calcium signaling has been pointed as a pathogenic mechanism of cortical dysfunction in MS. H...

Oligodendrocytes, the myelinating cells of the central nervous system, insulate axons with myelin, enabling rapid signal transmission, supporting neuronal metabolism, and contributing to brain plasticity. However, aging and neurodegenerative diseases can significantly impair oligodendrocyte function and myelin integrity. During aging, oligodendrocy...

Activation of the subventricular zone (SVZ) following cerebral ischemia is one of the brain’s early responses to counteract neuron loss and minimize tissue damage. Impaired brain regions communicate with the SVZ through various chemotactic signals that promote cell migration and differentiation, primarily involving neural stem cells (NSC), neurobla...

Neurodegenerative pathologies including multiple sclerosis (MS) are consistently associated with energy deficit in the central nervous system (CNS). This might directly impact myelinating oligodendrocytes as these are particularly vulnerable to metabolic insults. Importantly, oligodendroglial dysfunction and myelin alterations occur in most, if not...

Background Alzheimer’s disease (AD) plasma biomarkers related to amyloid (A), tau (T), and neurodegeneration (N) can potentially be used to identify these pathological features of the disease, as shown in recent studies. Our objective was to compare the clinical and analytical performance of plasma AD biomarkers measured using the single‐molecule a...

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a disorder mediated by autoantibodies against the GluN1 subunit of NMDAR. It occurs with severe neuropsychiatric symptoms that often improve with immunotherapy. Clinical studies and animal models based on patients’ antibody transfer or NMDAR immunization suggest that the autoantibodies play...

Activation of the subventricular zone (SVZ) following cerebral ischemia is one of the brain’s early responses to counteract neuron loss and minimize tissue damage. Impaired brain regions communicate with the SVZ through various chemotactic signals that promote cell migration and differentiation, primarily involving neural stem cells (NSC), neurobla...

IP3 receptor (IP3R)-mediated Ca²⁺ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial Ca²⁺ uptake and oxidative metabolism and is linked to different pathologies, including Parkinson’s disease (PD). The dependence of Ca²⁺ transfer efficiency on the ER-mitochondria distance remains unexplored. Employing...

Ischemic stroke is a complex brain pathology caused by an interruption of blood supply to the brain. It results in neurological deficits which that reflect the localization and the size of the compromised brain area and are the manifestation of complex pathogenic events triggered by energy depletion. Inflammation plays a prominent role, worsening t...

Multiple sclerosis (MS) is characterized by neuroinflammation and demyelination of the central nervous system (CNS), leading to disablility. Genetic variants that confer MS risk implicate genes involved in immune function, while variants related to severity of the disease are associated with genes preferentially expressed within the CNS. Current MS...

IP 3 receptor (IP 3 R)-mediated Ca ²⁺ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial Ca ²⁺ uptake and oxidative metabolism and is linked to different pathologies, including Parkinson’s disease (PD). The dependence of Ca ²⁺ transfer efficiency on the ER-mitochondria distance remains unexplored. Emp...

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a disorder mediated by autoantibodies against the GluN1 subunit of NMDAR. It occurs with severe neuropsychiatric symptoms that often improve with immunotherapy. Clinical studies and animal models based on patients' antibody transfer or NMDAR immunization suggest that the autoantibodies play...

Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in multiple sclerosis initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined...

We compared the clinical and analytical performance of Alzheimer’s disease (AD) plasma biomarkers measured using the single-molecule array (Simoa) and Lumipulse platforms. We quantified the plasma levels of amyloid beta 42 (Aβ42), Aβ40, phosphorylated tau (Ptau181), and total tau biomarkers in 81 patients with mild cognitive impairment (MCI), 30 wi...

Oligodendrocyte dysfunction, myelin degeneration, and white matter structural alterations are critical events in Alzheimer's disease (AD) that contribute to cognitive decline. A key hallmark of AD, Abeta oligomers, disrupt oligodendrocyte and myelin homeostasis, but a comprehensive global analysis of the mechanisms involved is lacking. Here, transc...

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these le...

Multiple sclerosis (MS) affects almost 3 million people globally who suffer demyelination as a series of relapses and remissions that tend towards progressive deterioration over time. The proximate cause is auto-immune attack by the adaptive immune system; therapies directed against this are effective during the relapsing-remitting phase but are le...

Activation of the subventricular zone (SVZ) after cerebral ischemia is one of the early responses in the brain to counteract the loss of neurons and reduce tissue damage. Impaired brain regions communicate with the SVZ through many chemotactic messages that result in neural stem cells (NSC) migration and differentiation. However, the activation of...

Activation of the subventricular zone (SVZ) after cerebral ischemia is one of the early responses in the brain to counteract the loss of neurons and reduce tissue damage. Impaired brain regions communicate with the SVZ through many chemotactic messages that result in neural stem cells (NSC) migration and differentiation. However, the activation of...

The study investigates brain lipid super-specialization by defining characteristic spectral lipotypic profiles for the five primary cerebral cell-types. Utilizing a computational approach, the research visualizes the anatomical distribution of these profiles in high spatial resolution brain tissues. This method unveils cellular stereotypic lipidic...

Background Alzheimer’s disease (AD) plasma biomarkers related to amyloid (A), tau (T), and neurodegeneration (N) can potentially be used to identify these pathological features of the disease, as shown in recent studies. Our objective was to compare the clinical and analytical performance of plasma AD biomarkers measured using the single-molecule a...

Activation of the subventricular zone (SVZ) after cerebral ischemia is one of the early responses in the brain to counteract the loss of neurons and reduce tissue damage. Impaired brain regions communicate with the SVZ through many chemotactic messages that result in neural stem cells (NSC) migration and differentiation. However, the activation of...

Recent evidence suggests that myelin lipids may act as glial energy reserves when glucose is lacking, a hypothesis yet to be solidly proven. Hereby, we examined the effects of running a marathon on myelin content by MRI. Our findings show that marathon runners undergo widespread robust myelin decrease at completion of the effort. This reduction inv...

The pathophysiological process of Alzheimer's disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its comprehensive characterization remains elusive. Accumulating evidence suggests that amyloid-β (Aβ) may media...

Recent evidence suggests that myelin lipids may act as glial energy reserves when glucose is lacking, a hypothesis yet to be solidly proven. Hereby, we examined the effects of running a marathon on the myelin content by MRI. Our findings show that marathon runners undergo widespread robust myelin decrease at completion of the effort. This reduction...

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play a vital role in maintaining the integrity of myelin, the protective sheath around nerve fibres essential for efficient signal transmission. However, in MS, oligodendrocytes become d...

Interferon regulatory factor 5 (IRF5), a transcription factor highly involved in innate immunity that drives microglia/macrophage towards a pro-inflammatory state, has been associated to multiple sclerosis susceptibility but its role in MS pathogenesis is unknown. Here we analysed the role of IRF5 in multiple sclerosis animal models. Irf 5 -/- mice...

Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis (MS) and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in MS initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we m...

There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating ph...

Nicotinic acetylcholine α7 receptors (α7 nAChRs) have a well-known modulator effect in neuroinflammation. Yet, the therapeutical effect of α7 nAChRs activation after stroke has been scarcely evaluated to date. The role of α7 nAChRs activation with PHA 568487 on inflammation after brain ischemia was assessed with positron emission tomography (PET) u...

Oxidized cholesterol metabolite 27-hydroxycholesterol (27-OH) is a potential link between hypercholesterolemia and neurodegenerative diseases since unlike peripheral cholesterol, 27-OH is transported across the blood-brain barrier. However, the effects of high 27-OH levels on oligodendrocyte function remain unexplored. We hypothesize that during hy...

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony s...

Adult oligodendrocyte progenitor cells (OPCs) give rise to myelinating oligodendrocytes through life and play crucial roles in brain homeostasis and plasticity during health and disease. Cannabinoid compounds acting through CB1 receptors promote the proliferation and differentiation of OPCs in vitro and facilitate developmental myelination and myel...

Microcircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the function of cortical microcircuits has focused on neuronal elements, much less is known about the functional organization of astrocytes and their bidirectional interaction with neurons....

Promoting remyelination is considered as a potential neurorepair strategy to prevent/ limit the development of permanent neurological disability in patients with multiple sclerosis (MS). To this end, a number of clinical trials are investigating the potential of existing drugs to enhance oligodendrocyte progenitor cell (OPC) differentiation, a proc...

Oligodendrocytes are the myelin forming cells of the central nervous system, and their vulnerability to excitotoxicity induced by glutamate contributes to the pathogenesis of neurological disorders including brain ischemia and neurodegenerative diseases, such as multiple sclerosis. In addition to glutamate receptors, oligodendrocytes express GABA r...

Synapses represent an important target of Alzheimer disease (AD), and alterations of their excitability are among the earliest changes associated with AD development. Synaptic activation has been shown to be protective in models of AD, and deep brain stimulation (DBS), a surgical strategy that modulates neuronal activity to treat neurological and p...

Preventing neurodegeneration-associated disability progression in patients with multiple sclerosis (MS) remains an unmet therapeutic need. As remyelination prevents axonal degeneration, promoting this process in patients might enhance neuroprotection. In demyelinating mouse lesions, local overexpression of semaphorin 3F (Sema3F), an oligodendrocyte...

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony s...

Cannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precursor cell (OPC)-targeted genetic mouse models, we sho...

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony s...

Evidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer’s disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is associated with altered patterns of resting-state fun...

Glial cells participate actively in the early cognitive decline in Alzheimer’s disease (AD) pathology. In fact, recent studies have found molecular and functional abnormalities in astrocytes and microglia in both animal models and brains of patients suffering from this pathology. In this regard, reactive gliosis intimately associated with amyloid p...

Glial cells are essential to understand Alzheimer’s disease (AD) progression, given their role in neuroinflammation and neurodegeneration. There is a need for reliable and easy to manipulate models that allow studying the mechanisms behind neuron and glia communication. Currently available models such as co-cultures require complex methodologies an...

The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid Δ9‐tetrahydrocannabinol (Δ9‐THC) in late 1980s paved the way for investigations on the effects of cannabis‐based therapeutics in brain pathology. Ever since, a wealth of results obtained from studies on human tissue samples and animal models have hig...

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promi...

Amyloid beta (Aβ)-mediated synapse dysfunction is an early event in Alzheimer’s disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Aβ peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in the early stages of AD...

Microcircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the function of cortical microcircuits has focused on neuronal elements, much less is known about the functional organization of astrocytes and their bidirectional interaction with neurons....

Introduction Blood and cerebrospinal fluid represent emerging candidate fluids for biomarker identification in Parkinson's disease (PD). Methods We studied 8 individuals carrying the E46K-SNCA mutation (3 PD dementia (PDD), 1 tremor-dominant PD, 2 young rigid-akinetic PD and 2 asymptomatic) and 8 age- and sex-matched healthy controls. We quantifie...

Promoting remyelination - the endogenous response by which lost myelin sheaths are regenerated - is considered as a potential neuroprotective strategy to prevent/limit the development of permanent neurological disability in patients with multiple sclerosis (MS). To this end, a number of clinical trials are investigating the potential of existing dr...

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promi...

Glial cells are essential to understand Alzheimer’s disease (AD) progression, given their role in neuroinflammation and neurodegeneration. There is a need for reliable and easy to manipulate models that allow studying the mechanisms behind neuron and glia communication. Currently available models such as cocultures require complex methodologies and...

The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we generated induced pluripotent stem cells (iPSC)-derived as...

Background: Midlife hypercholesterolemia is an established risk factor for developing Alzheimer's disease (AD), still peripheral cholesterol does not pass the blood-brain-barrier (BBB). A proposed factor linking elevated systemic cholesterol levels and AD is the oxidized cholesterol metabolite 27-hydroxycholesterol (27-OH) that can pass the BBB. A...

Background Although Alzheimer’s disease (AD) is associated with alterations of the central nervous system, this disease has an echo in blood that might represent a valuable source of biomarkers for improved diagnosis, prognosis and for monitoring drug response. Methods We performed a targeted transcriptomics study on 38 mild Alzheimer’s disease (A...

Specific and selective anti-CB 1 antibodies are among the most powerful research tools to unravel the complex biological processes mediated by the CB 1 receptor in both physiological and pathological conditions. However, low performance of antibodies remains a major source of inconsistency between results from different laboratories. Using a variet...

Background and purpose Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery. Δ⁹‐Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neurop...

Microglia act as sensors of injury in the brain, favoring its homeostasis. Their activation and polarization toward a proinflammatory phenotype are associated with injury and disease. These processes are linked to a metabolic reprogramming of the cells, characterized by high rates of glycolysis and suppressed oxidative phosphorylation. This metabol...

Introduction: There is evidence that early intervention contributes to improving the prognosis and course of first-episode psychosis (FEP). However, further randomised treatment clinical trials are needed. Objectives: The aim of this study was to compare the efficacy of a combined clinical treatment involving Cognitive Behavioural Therapy (CBT)...

Cover Illustration: Tetrahydrocannabinol administration at early postnatal ages to CNP‐mGFP mice increases mature myelinating oligodendrocyte cell density in the developing white matter. CNP (2′,3′‐Cyclic nucleotide 3′‐phosphodiesterase; green) and MAG (myelin‐associated glycoprotein; red). (See Huerga‐Gómez, A. et al, https://doi.org/10.1002/glia....

Background: Research on demyelinating disorders aims to find novel molecules able to induce oligodendrocyte precursor cell differentiation to promote CNS remyelination and functional recovery. Δ9-Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neuroprotection in animal models of demyelina...

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the diffe...

Adenosine A1 receptors (A1ARs) are promising imaging biomarkers and targets for the treatment of stroke. Nevertheless, the role of A1ARs on ischemic damage and its subsequent neuroinflammatory response has been scarcely explored so far. Methods: In this study, the expression of A1ARs after transient middle cerebral artery occlusion (MCAO) was evalu...

In Alzheimer’s disease (AD), amyloid β peptide (Aβ) causes mitochondrial alterations including disrupted metabolism and dynamics, enhanced oxidative stress, aberrant calcium signaling, and neuronal apoptosis. Natural polyphenols boost mitochondria and bioenergetic function as well as exhibit neuroprotective effects in experimental paradigms that ar...

Background Amyloid beta (Aβ)-mediated synapse dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Aβ peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in early stages...

Microglia act as sensors of injury in the brain, favouring its homeostasis. Their activation and polarization towards a pro-inflammatory phenotype are associated to injury and disease. These processes are linked to a metabolic reprogramming of the cells, characterized by high rates of glycolysis and suppressed oxidative phosphorylation. This metabo...

Oligodendrocytes (OLs) express functional GABAA receptors (GABAARs) that are activated by GABA released at synaptic contacts with axons or by ambient GABA in extra-synaptic domains. In both instances, the receptors molecular identity has not been fully defined. Furthermore, data on their structural diversity in different brain regions, and informat...

Background Changes in synaptic excitability and reduced brain metabolism are among the earliest alterations associated with the development of Alzheimer’s disease (AD) (Reiman et al., 2004; Sperling et al., 2009). Among different approaches for therapeutics, the stimulation of synaptic activity has been shown to be protective in models of AD, and d...

The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homeostatic support and deficient neuroprotection. In this study, we generated iPSC-derived astrocytes from PD patients with LRR...

Parkinson's disease (PD) affects millions of patients worldwide and is characterized by alpha-synuclein aggregation in dopamine neurons. Molecular tweezers have shown high potential as anti-aggregation agents targeting positively charged residues of proteins undergoing amyloidogenic processes. Here we report that the molecular tweezer CLR01 decreas...

d9-Tetrahydrocannabinol (THC), the main bioactive compound found in the plantCannabis sativa, exerts its effects by activating cannabinoid receptors present in manyneural cells. Cannabinoid receptors are also physiologically engaged by endogenouscannabinoid compounds, the so-called endocannabinoids. Specifically, the endo-cannabinoid 2-arachidonoyl...

The endocannabinoid system is associated with protective effects in multiple sclerosis (MS) that involve attenuated innate immune cell responses. Astrocytes and microglia are modulated by endocannabinoids and participate in the biosynthesis and metabolism of these compounds. However, the role of neuroglial cells as targets and mediators of endocann...

Sephin1 is a derivative of guanabenz that inhibits the dephosphorylation of the eukaryotic initiation factor 2 alpha (eIF2α) and therefore may enhance the integrated stress response (ISR), an adaptive mechanism against different cellular stresses, such as accumulation of misfolded proteins. Unlike guanabenz, Sephin1 provides neuroprotection without...

The release and extracellular action of ATP are a widespread mechanism for cell-to-cell communication in living organisms through activation of P2X and P2Y receptors expressed at the cell surface of most tissues, including the nervous system. Among ionototropic receptors, P2X4 receptors have emerged in the last decade as a potential target for CNS...

Myelin facilitates the fast transmission of nerve impulses and provides metabolic support to axons. Differentiation of oligodendrocyte progenitor cells (OPCs) and Schwann cell (SC) precursors is critical for myelination during development and myelin repair in demyelinating disorders. Myelination is tightly controlled by neuron-glia communication an...

In vivo positron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far. In vivo and ex vivo assessment of gliogenesis after transient middle cerebral artery occlusi...