Regionally specific age-dependent decline in α 2-adrenoceptors: An autoradiographic study in human brain

The effect of sex, postmortem delay and aging on alpha 2-adrenoceptor binding was studied in tissue sections from several representative regions of the human brain from 21 subjects using [3H]UK-14304 as a ligand. Sex and postmortem delay did not influence the density of alpha 2-receptors. Aging resulted in clear decreases in most forebrain areas examined (n. basalis greater than basal ganglia greater than hypothalamus greater than fronto-temporal cortex greater than hippocampus greater than visual cortex), whereas alpha 2-receptors did not significantly change with age in the amygdala and several infratentorial areas. We conclude that age-related, regionally specific decreases in the density of alpha 2-receptors occur in the human brain. The implications of these findings for age-dependent noradrenergic degeneration are discussed.

[1]  J. Palacios,et al.  Distribution of α2-adrenergic receptors in the human brainstem: An autoradiographic study using [3H]p-aminoclonidine , 1984 .

[2]  P. Yates,et al.  The noradrenergic system in Alzheimer and multi-infarct dementias. , 1982, Journal of neurology, neurosurgery, and psychiatry.

[3]  P. Yates,et al.  The pathology of the human locus ceruleus. , 1983, Clinical neuropathology.

[4]  W. Bondareff,et al.  Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia , 1982, Neurology.

[5]  W. Weiner,et al.  Nerve growth factor and Alzheimer's disease , 1986, Annals of neurology.

[6]  N. Volkow,et al.  Age‐related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET) , 1990, Journal of neuroscience research.

[7]  P. Yates,et al.  The topography of cell loss from locus caeruleus in Alzheimer's disease , 1986, Journal of the Neurological Sciences.

[8]  S. Z. Langer.  Presynaptic regulation of the release of catecholamines. , 1980, Pharmacological reviews.

[9]  B. Winblad,et al.  Changes in the Brain Catecholamines in Patients with Dementia of Alzheimer Type , 1979, British Journal of Psychiatry.

[10]  Y. Agid,et al.  Adrenergic receptors in Parkinson's disease , 1984, Brain Research.

[11]  J. García-Sevilla,et al.  Characterization and Regional Distribution of α2‐Adrenoceptors in Postmortem Human Brain Using the Full Agonist [3H]UK 14304 , 1989, Journal of neurochemistry.

[12]  T. Taniguchi,et al.  Biochemical Characterization of α‐Adrenergic Receptors in Human Brain and Changes in Alzheimer‐Type Dementia , 1986 .

[13]  Á. Pazos,et al.  High-affinity choline uptake carrier in Alzheimer's disease: implications for the cholinergic hypothesis of dementia , 1991, Brain Research.

[14]  T. Crow,et al.  Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type , 1984, Journal of the Neurological Sciences.

[15]  H Brody,et al.  A QUANTITATIVE STUDY OF THE PIGMENTED NEURONS IN THE NUCLEI LOCUS COERULEUS AND SUBCOERULEUS IN MAN AS RELATED TO AGING , 1979, Journal of neuropathology and experimental neurology.

[16]  T. Joh,et al.  Evidence for retrograde degeneration of epinephrine neurons in Alzheimer's disease , 1988, Annals of neurology.

[17]  T. Joh,et al.  Phenylethanolamine N‐methyltransferase activity is decreased in Alzheimer's disease brains , 1987, Annals of neurology.

[18]  Á. Pazos,et al.  α2-Adrenoceptors in human forebrain: autoradiographic visualization and biochemical parameters using the agonist [3H]UK-14304 , 1988, Brain Research.

[19]  F. E. Bloom,et al.  Loss of pigmented dopamine-β-hydroxylase positive cells from locus coeruleus in senile dementia of alzheimer's type , 1983, Neuroscience Letters.

[20]  Michael J. Kuhar,et al.  Quantitative receptor autoradiography using [3H]Ultrofilm: application to multiple benzodiazepine receptors , 1982, Journal of Neuroscience Methods.