Jaime Grutzendler MD
Associate Professor of Neurology and of Neurobiology; Director, Yale Center for Experimental Neuroimaging (YCEN)
Research Interests
Two-photon microscopy; Neurodegeneration; Alzheimer's; Blood-brain barrier; Microvasculature; Synapses; Neuroinflammation; Microglia; Astrocyte; Endothelium, myelin imaging
Current Projects
Research Summary
The overall interest of our laboratory centers around cells in the so called "neurovascular unit" (neurons, endothelium, astrocytes, pericytes and microglia). We aim at learning about the dynamic properties of these cells and how cell-cell interactions are disrupted in brain injury, vascular and neurodegenerative pathologies. Experiments in the laboratory involve mouse models of various cerebral disorders including microvascular injury and Alzheimer's disease. The majority of projects in the laboratory are imaging-oriented. We use a variety of techniques including transcranial in vivo two photon microscopy, high-resolution confocal and electron microscopy in combination with differential fluorescent cell labeling and genetic/pharmacological manipulations.
Extensive Research Description
- We develop strategies using two-photon microscopy (TPM) and confocal microscopy to repeatedly image individual neurons, dendritic spines, microglia, astrocytes, blood vessels and myelin over periods of up to months in the brain of living mice in the context of injury and degenerative pathologies.
- We are interested in understanding the dynamics of various neurodegenerative conditions such as Alzheimer's disease. Specifically we are interested in the interactions between microglia, neurons and amyloid plaques to determine the potential role of microglia in plaque formation, removal and secondary neuronal injury
- Vascular mechanisms of neuronal circuit disruption: we are interested in understanding how neurons and astrocytes adapt to metabolic challenges such as chronic focal and global hypoperfusion and hypoxia. We also investigate mechanisms of microvascular recanalization and angioplasticity after cerebral embolic occlusion. Specifically, we have recently described a previously unrecognized mechanism of microvascular plasticity which leads to vessel recanalization. We are currently investigating the molecular control and physiological relevance of this novel mechanism.
Selected Publications
- Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization. Lam CK, Yoo T, Hiner B, Liu Z, Grutzendler J. Nature. 2010 May 27;465(7297):478-82.
- CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar amyloid-ß phagocytosis. Liu Z, Condello C, Schain A, Harb R, Grutzendler J. J Neurosci. 2010 Dec 15;30(50):17091-101.
- Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition. C. Condello, A. Schain, J. Grutzendler. Scientific Reports. 2011. 1,19. doi:10.1038/srep00019.
- In vivo imaging of cerebral microvascular plasticity from birth to death. Harb R, Whiteus C, Freitas C, Grutzendler J. J Cereb Blood Flow Metab. 2012 Oct 24.
- Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer's disease. Grutzendler J, Helmin K, Tsai J, Gan WB. Ann N Y Acad Sci. 2007 Feb;1097:30-9.
- ATP mediates rapid microglial response to local brain injury in vivo. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. Nat Neurosci. 2005 Jun;8(6):752-8.
- Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Tsai J, Grutzendler J, Duff K, Gan WB. Nat Neurosci. 2004 Nov;7(11):1181-3
- Long-term dendritic spine stability in the adult cortex. Grutzendler J, Kasthuri N, Gan WB. Nature. 2002 Dec 19-26;420(6917):812-6.
