Jonathan Kipnis, Ph.D.
Ph.D., 2004, Weizmann Institute of
Professor of Neuroscience
Director, Center for Brain Immunology and Glia (BIG)
Laboratory of Cellular and Molecular Neuroimmunology
Neuro-Immune interactions in neurodegenerative, mental,
cognitive and neurodevelopmental disorders – understanding of basic
mechanisms and development of novel therapies and vaccines.
Kipnis Lab Website
In my lab we are working to better understand the complex interactions between the immune and nervous systems. Until very recently, scientists assumed that any activity of the immune system within or around the central nervous system (CNS) was a hallmark of pathology. However, multiple new lines of evidence support the notion that immune support is actually required for optimal neuronal survival following CNS injury.
In parallel, we recently showed that immune-compromised mice exhibit behavioral and cognitive abnormalities when compared to mice with normally-functioning immune systems. Animals that lack the population of unique T lymphocytes, or key molecular factors produced by these cells, are strikingly impaired in learning and memory tasks, adult neurogenesis, and neuronal plasticity. Moreover, a well-controlled boost of immune response improves learning abilities in normal animals and accelerates the process of neurogenesis.
Our goal is to elucidate the cellular and molecular mechanisms underlying the beneficial effects of immune cells in healthy and diseased CNS. On the therapeutic “frontline”, we are designing vaccines and developing novel therapies with a potential to promote neuronal survival, improve cognitive functions, and slow down progression of neurodegenerative, neurodevelopmental and cognitive disorders.
We are studying the following areas:
CNS injury and neurodegenerative diseases - neuronal regeneration, neuroprotection, and neurogenesis.
Models: stroke, spinal cord injury, optic nerve injury, brain injury, glaucoma, Alzheimer's Disease.
Cognitive and mental disorders – impairment of cognition, neurogenesis, and neuronal plasticity; glial biology.
Models: age-related dementia, chemo-brain, Alzheimer's Disease, schizophrenia, and depression.
To learn more about the role of immunity in cognitive function, take a look at this Scientific American Blog post on our research.
Neurodevelopmental disorders – neurogenesis, neuronal plasticity, synapse formation and maintenance, glial biology.
Models: autism spectrum disorders, Rett syndrome.
|Wild type and immune deficient (scid) mice were compared at cognitive task performance on Barnes Maze (the aim is to find a hidden box within the shortest time). Note the difference in the path length between the two strains.|
|Brains from wild type and immune deficient (scid) mice were analyzed for synapses using electron microscope. Note the difference in the numbers of synapses (marked by red arrow heads) between wild type and scid mice.|
|Primary neurons are grown in cultures and make spontaneous connections (synapses). Stimulations by T cells significantly increase the numbers of synapses.|
|Brains from wild type and immune deficient (scid) mice were analyzed for newly born neurons (green) and neural stem cells (red) using confocal microscope. Note the difference in the numbers of neuronal and neural progenitors between wild type and scid mice.|
Selected Recent Publications
Lu Z, Kipnis J. (2010) Thrombospondin 1--a key astrocyte-derived neurogenic factor. FASEB J. Jun;24(6):1925-34.
Derecki NC, Privman E, Kipnis J. (2010) Rett syndrome and other autism spectrum disorders--brain diseases of immune malfunction? Mol Psych. Apr;15(4):355-63. Epub 2010 Feb 23.
Derecki NC, Cardani AN, Yang CH, Quinnies KM, Crihfield A, Lynch KR, Kipnis J. (2010) Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med. May 10;207(5):1067-80. Epub 2010 May 3.
Walsh JT, Kipnis J. (2011) Regulatory T cells in CNS injury: the simple, the complex, and the confused. Trends Mol Med. Oct;17(10):541-7.
Lu Z, Elliott MR, Chen Y, Walsh J., Klibanov, AI, Ravichandran KS, Kipnis J. (2011) A novel phagocytic role for neural progenitors that regulates adult neurogenesis. Nat Cell Biol. Jul 31:13(9):1076-83.
Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SBG, Guyenet PG, Kipnis J. (2012) Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature. 2012 Mar 18;484(7392):105-9.
Kipnis J, Gadani S, Derecki NC. (2012) Pro-cognitive properties of T cells. Nat Rev Immunol. 2012 Aug 10;12(9):663-9.