The gastrointestinal tract is a huge, complex bioactive barrier surface, allowing sensing, signal transduction and communication between the outside world and our body. We study various components of the gut microenvironment:
The intestinal epithelium and gut barrier
Enteric glial cells
Sympathetic and parasympathetic nerve fibers
We investigate the physiological functions of these components in a holistic approach, allowing better understanding of neurological diseases in the context of aging.
We study how processes which take place in the gut, affect brain functions in health and disease, and looking at the whole-organism level to identify novel targets to treat brain pathologies
Aging is a major risk factor for numerous brain pathologies, and is accompanied by changes in metabolic, immunological, neurological and hormonal functions. Given the expanding aging demographic, there is an urgent need to better define the molecular and cellular mechanisms responsible for increased susceptibility to neurological disorders of aged individuals.
We carry out longitudinal pre-clinical studies in young and aged mice to elucidate systemic, long-term processes that predispose the aging organism to develop neurological damage.
The gut-brain axis
The gut harbors the biggest reservoir of immune cells in the body. At the same time, it constitutes an ecosystem for trillions of bacteria that constantly biochemically interact with the host and is continuously innervated by enteric neurons and autonomic nerves interconnecting with the brain. Being such a central, bioactive barrier surface, it is surprising how little is known about basic intestinal biological processes that may affect the structure and function of the nervous system.
We study the gut-brain communication in aging and neurological disorders. In particular, we are interested in mechanisms of gut-barrier dysfunction following acute brain injuries, such as stroke and head trauma, chronic (neurodegeneration) and during brain tumors’ progression.
Gut bacteria - the microbiome - and their associated metabolites can influence the progression of neurodegenerative diseases. Identifing and targeting those bacteria and metabolic pathways may serve as a novel approach to treat neurological disorders. Image adapted from Blacher E, Science 2021.
With an ever-increasing aging population, diseases such as Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS) are on the rise and this trend is projected to
continue. These devastating diseases take away the patient’s independence by gradually destroying the patient’s motor abilities, communication skills, memory and clear line of thought.
By using multi-omics approaches on both the microbiome and the host, we study metabolic pathways that contribute to neurodegeneration and modulate them as a pre-clinical therapeutic strategy.
Confocal microscopy image of a brain slice taken from a mouse model for Alzheimer's disease. In red shown disease-associated aggregations (Aβ plaques). Microglia, the immune cells of the brain, is shown in green, surround and infiltrates the plaques. Some of the cells engulf pieces of the plaque with their processes. Other brain cells, such as neurons, are shown in blue. Image taken by: Eran Blacher.
Immune cells metabolism
The composition, function, and polarization state of the immune system change profoundly in aging and in various neurological diseases. Underlying a progressive loss of immune homeostasis in aging, there is a sharp decline in myeloid cell bioenergetics.
We are interested in identifying novel metabolic pathways that rejuvenate immune-related functions. By targeted metabolic reprogramming of specific immune cells, we aim at reversing age-related pathological phenotypes.
Microglia are the resident innate immune cells of the brain. Their metabolism changes with aging and disease, and can impact various pathologies, such as brain tumors. Right: Light microscopy image of microglial cells in culture. Left: CT imaging of glioma bearing mice.
Image taken by: Eran Blacher.