The New York Consortium in Evolutionary Primatology
Regenstreif Professor and Vice-Chair Department of Neuroscience Mount Sinai School of Medicine
M.D., 1985, University of Geneva School of Medicine
Email: patrick.hof [at] mssm.edu
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. We also investigate transgenic mouse models, expressing the human tau gene or mutations in the amyloid precursor protein. We study spatial and temporal relationships between neuronal integrity and reflections of degeneration such as tangle formation, amyloid deposition and microvascular damage. We employ high field magnetic resonance microscopy, stereologic, and mathematical modeling approaches to develop an accurate quantitative appraisal of such pathological changes in a cortical region- and layer-specific manner. 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 in the context of schizophrenia and autism spectrum disorder.
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, judgement, and attention, that can be considered as markers of adaptive mechanisms and functions in response to particular ecological pressure.
Hof PR, Morrison JH. The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 2004; 27: 607-613.
Hof PR, Van der Gucht E. The structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae). Anat Rec 2007; 290: 1-31.
Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, McEwen BS, Morrison JH, Wearne SL, Hof PR. Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J Comp Neurol 2008; 507: 1141-1150.
Akram A, Christoffel D, Rocher AB, Bouras C, Kövari E, Perl DP, Morrison JH, Herrmann FR, Haroutunian V, Giannakopoulos P, Hof PR. Stereologic estimates of total spinophilin-immunoreactive spine numbers in area 9 and the CA1 field: relationship with the progression of Alzheimer's disease. Neurobiol Aging 2008; 29: 1296-1307.
Kabaso D, Koskren PJ, Henry BI, Hof PR, Wearne SL. The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cereb Cortex 2009; 19: 2248-2268.
Sherwood CC, Stimpson CD, Butti C, Bonar CJ, Newton AL, Allman JM, Hof PR. Neocortical neuron types in Xenarthra and Afrotheria: implications for brain evolution in mammals. Brain Struct Funct 2009; 213: 301-328.
Butti C, Sherwood CC, Hakeem AY, Allman JM, Patrick R. Hof PR. Total number and volume of von Economo neurons in the cerebral cortex of cetaceans. J Comp Neurol 2009; 515: 243-259.
Luebke JI, Weaver CM, 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.
Butti C, Hof PR. The insular cortex: a comparative perspective. Brain Struct Funct 2010; 214: 477-493.
Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, Goubert V, Hof PR. The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Struct Funct 2010; 214: 495-517.
Sherwood CC, Raghanti MA, Stimpson CD, Spocter MA, Uddin M, Boddy AM, Wildman DE, Bonar CJ, Lewandowski AH, Phillips KA, Erwin JM, Hof PR. Inhibitory interneurons of the human prefrontal cortex display conserved evolution of the phenotype and related genes. Proc R Soc B 2010; 277: 1011-1020.