Our research is directed towards the study of selective neuronal vulnerability in dementing illnesses using classical neuropathological as well as modern quantitative immunohistochemical methods. We intend to develop a quantitative, detailed and cohesive definition of neuronal susceptibility to degeneration in the cerebral cortex, by extending data on Alzheimer disease to other dementing disorders as well as animal models of age-related illnesses, and by defining the key neurochemical and morphological characteristics linked to relative vulnerability (or resistance to degeneration) of identified neuronal populations. The regional and laminar distribution in the cerebral cortex of specific neuronal populations is investigated in a variety of neurodegenerative disorders, and quantitatively compared to Alzheimer disease and control brains. In addition, a detailed study of brains from aged patients with no records of neurological and psychiatric disorders is performed in order to define further the limits of normal aging in the brain.
We employ advanced microscopy, high field magnetic resonance imaging, stereologic, and modeling approaches to develop an accurate quantitative assessment of such pathological changes in a region- and layer-specific manner. Neuronal morphology is analyzed in a quantitative manner using intracellular injection of hippocampal and neocortical neurons coupled with computerized reconstruction to assess the degree to which the accumulation of pathologic markers causes dendritic atrophy and spine loss in different subtypes of neocortical pyramidal cells subserving cortical circuits critical for memory and cognition. The characterization of such vulnerable neurons and circuits is fundamental to the design of therapeutic strategies aiming at their protection or rescue. Similar approaches are applied to the neuropathology of schizophrenia and autism.
Finally we are investigating mammalian brain evolution with a focus on cetaceans and great apes. These studies have led us to identify specific neuronal types in parts of the cerebral cortex known to be involved in social awareness, judgment, and attention that can be considered as markers of adaptive mechanisms and functions in response to particular ecological pressure.
|Luebke JI, Weaver C, Rocher AB, Rodriguez A, Crimins JL, Dickstein DL, Wearne SL, Hof PR. Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models. Brain Struct. Funct. 2010; 214: 181-199.||
Patrick Hof, MD
|Dr. Hof is the Regenstreif Professor of Neuroscience and Vice-Chair of the Department of Neuroscience.|
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