Projektbeschreibung
Neue Forschung zur Neurogenese im Hippocampus Erwachsener
Der Hippocampus ist ein Areal im Gehirn, das Lernen und Gedächtnis steuert. An Nagermodellen wurde bereits ein Zusammenhang zwischen gestörter Neurogenese im Hippocampus Ausgewachsener und kognitiven Fehlleistungen sowie Stimmungsschwankungen festgestellt. Besonders anfällig für Schäden ist der Hippocampus in den ersten Frühstadien von Alzheimer. So untersucht das vom Europäischen Forschungsrat finanzierte Projekt HumAN, welche Mechanismen die Reifung und synaptische Integration neu erzeugter Zellen beim Menschen regulieren. Dies wird auch neue Erkenntnisse zur Pathophysiologie neurodegenerativer und psychischer Krankheiten sowie mögliche neue therapeutische Ansätze für diese bislang unheilbaren Erkrankungen liefern. Erstmals wird das Projekt zudem untersuchen, wann sich neue Neuronen effizient in den menschlichen Hippocampus integrieren.
Ziel
The hippocampus is crucial for learning and memory and it hosts an extraordinary form of plasticity: the generation of new neurons throughout life, a process named adult hippocampal neurogenesis (AHN). Newly generated neurons grow in a specialised niche composed of unique vascular, glial, and neuronal elements. Impaired AHN leads to cognitive dysfunction and mood dysregulation in rodents. Recent work by my group reveals the persistence of AHN until the tenth decade of human life, as well as impairment of this process in patients with Alzheimer’s disease. The general aim of HumAN is to unveil the features that confer the human hippocampus with neurogenic potential, thoroughly characterising this niche in adulthood, physiological aging, and pathological conditions (AIM 1), and to identify potentially unique AHN signatures for specific neurodegenerative and psychiatric diseases (AIM 2). Moreover, we will determine, for the first time, whether new neurons integrate efficiently into the human hippocampus (AIM 3) and we will interrogate the subcellular machinery of these cells to unravel the mechanisms underlying AHN impairments in these diseases (AIM 4). The unprecedented quality of our collection of human hippocampal samples, obtained from 180 individuals (either controls or with specific neurodegenerative or psychiatric diseases), allows successful application of trail-blazing methodologies such as RNAscope, iterative indirect immunofluorescence imaging (4i)-microscopy, and super-resolution and stimulated emission depleted (STED) nano-resolution microscopy. HumAN will break new ground in the field of AHN by deepening our understanding not only of the mechanisms that control the maturation and synaptic integration of newly generated cells in human beings, but also of the pathophysiology of neurodegenerative and psychiatric diseases, thereby facilitating the identification of potential novel therapeutic targets for these as yet incurable conditions.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
28006 Madrid
Spanien