Dr. Carlos Matute was appointed Scientific Director of ACHUCARRO from 2012 until the end of 2020.
He graduated in Physical Sciences from the University of Zaragoza. Later on, he became interested in Neuroscience and did his Doctoral Thesis under the supervision of Dr. Luis Martínez-Millán at the Department of Anatomy from the Faculty of Medicine at the University of Zaragoza. He obtained his PhD in 1982 and received an Extraordinary Award for his Thesis entitled “Experimental study of the distribution of neurotransmitters in the cortico-collicular and tecto -thalamic pathways”.
His initial work focused on the characterization of glutamatergic connections in the Central Nervous System (CNS). These chemo-neuroanatomical studies on brain connections were further developed during his first postdoctoral stay at the Brain Research Institute at the University of Zurich (Switzerland) under the supervision of Drs. Michel Cuénod and Peter Streit. During his stay in Zürich, he generated monoclonal antibodies against excitatory and inhibitory neurotransmitters (glutamate, aspartate, GABA and glycine) which allowed them to pioneer the characterization of nerve connections that used these amino acids as neurotransmitters. These antibodies have been distributed for free on demand, and used in hundreds of laboratories all over the world.
Carlos then moved to the laboratory of Dr. Ricardo Miledi (Prince of Asturias Award for Research 1999) at the University of California in Irvine. One of the most important findings during his stay with Dr. Miledi, and which would later serve as the basis for his research activity in the Basque Country, was that glial cells expressed functional receptors for neurotransmitters.
After his return to Spain, he joined the University of the Basque Country and in 1988 founded the Laboratory of Neurobiology at the Department of Neurosciences. His lab is specialized in glial cell biology. Glial cells constitute, together with neurons, the two main types of cells of the Central Nervous System (CNS). Traditionally, it has been considered that these cells, among which are astrocytes, oligodendrocytes and microglial cells, provided sustenance for the correct functioning of neurons, limiting their functions to structural and metabolic support. However, the work of several research groups, including Dr. Matute’s, showed that these cells expressed receptors for neurotransmitters on their membranes, and thus, contribute directly to brain communication. This discovery has served as the basis for the establishment of the now widely accepted theory that glial cells play a more active role than previously believed in the processing and transmission of nerve impulses and, therefore, in cognition.
Another significant discovery by him is that oligodendrocytes express AMPA and kainate glutamate receptors, whose excessive activation causes their own death. This phenomenon, initially described in neurons, is known as excitotoxicity. Oligodendrocytes are the cells responsible for myelination of axons in the CNS, which is needed for fast transmission of nerve impulses. Consequently, myelin damage impairs nerve impulse conduction and disrupts proper brain function. Demyelination is precisely the hallmark of multiple sclerosis, a neurodegenerative disease that can affect the entire CNS. The pioneering work of Dr. Matute and his team led to establishing the idea that excitotoxicity isa major cause of oligodendrocyte death and demyelination in this disease opening new avenues for novel neuroprotective therapies. Lately, his laboratory has contributed to the idea that NMDA receptors in oligodendrocytes are key to support energy demand of axons, and that disruption of their activity in anti-NMDA receptor autoimmune encephalitis underlies white matter damage and connectivity alterations in this rare disease.
Carlos Matute has also contributed to a better understanding of another excitatory neurotransmitter, ATP, which can also cause receptor-mediated oligodendroglial death. Interestingly, he has shown that receptor antagonists for ATP diminish tissue damage and ameliorates neurological symptoms in experimental multiple sclerosis, and stroke. More recently, his laboratory has also discovered that purinergic receptors play a relevant role in microglial response to myelin injury, a finding that also has a high potential for clinical translation.
Currently, Carlos is studying myelin autophagy by oligodendroglia and how it is regulated by glutamate and ATP receptors. This opens intriguing questions that he is addressing about the metabolic relevance of this feature its impact in shaping the oligodendrocyte population as well as in myelin generation and maintenance.
Keep connected for more exciting news on these developments.