title: Communication among neurons.
abstract: The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues.   Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for.   Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are considered and the relation to the prevailing beta-amyloid hypothesis is discussed.
authors.affiliation: PET and Cyclotron Unit, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. lisbeth@marner.dk
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Marner
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000502:physiology*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated; D009474:Neurons / Q000502:physiology*; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000502:physiology; D012559:Schizophrenia / Q000473:pathology; D013223:Statistics as Topic; D055815:Young Adult