Effects of aging on signal transmission and transduction systems in the gerbil brain: morphological and autoradiographic study.
The Mongolian gerbil was used as a model of aging because of its relatively short lifespan, genetic homogeneity and the fact that data had been collected previously. Furthermore, gerbils have been widely used in biomedical investigations of stroke and epilepsy. Age-related differences in signal transmission and transduction systems were investigated in brains of three-, 11- and 21-month-old gerbils by morphological and in vitro receptor autoradiographic studies. Morphometric analysis revealed a decreased number of neurons in layer III of the occipital cortex and also a decrease in cerebellar Purkinje cells in 21-month-old animals. However, no statistical differences were observed in the hippocampal formation, the dorsolateral striatum and layer III of the frontal cortex. Autoradiography was used to map muscarinic cholinergic (labeled with [3H]quinuclidinyl benzilate), serotonin2 ([3H]spiperone), dopamine D2 ([3H]spiperone), adenosine A1 ([3H]cyclohexyladenosine), GABAA ([3H]muscimol), naloxone ([3H]naloxone), protein kinase C ([3H]phorbol 12,13-dibutyrate), adenylate cyclase ([3H]forskolin), cyclic AMP ([3H]cyclic AMP) and L-type Ca2+ channels ([3H]PN200-110). Muscarinic cholinergic receptor and protein kinase C, cyclic AMP and L-type Ca2+ channels were significantly decreased in the cerebral cortex and/or in the CA1 subfield of the hippocampus in the 21-month-old group. Muscarinic cholinergic receptor and L-type Ca2+ channel binding sites were significantly reduced in the dentate gyrus. In contrast, protein kinase C was increased in this area in the 21-month-old group. Also, naloxone binding sites were increased in the CA3 subfield, hilus, dentate gyrus and molecular layer of the cerebellum in the 11- and 21-month-old groups. Muscarinic cholinergic, serotonin2 and dopamine D2 receptors and adenylate cyclase were significantly decreased in the striatum. On the other hand, adenosine A1 and GABAA receptors remained unchanged in the 21-month-old group. Although age-related histopathological abnormalities were only observed in the occipital cortex and in the cerebellum, alterations of signal transmission and transduction systems were noticed in all areas examined (e.g. cerebral cortex, CA1 subfield, dentate gyrus and striatum). These data indicate that changes in these receptors and binding sites may be related to dysfunction of learning and memory and to the loss of motor function. The aged gerbil model is a good system for studying aging and is of value for simulating aging after epilepsy and stroke.
Department of Neurology, Institute of Brain Diseases, Tohoku University School of Medicine, Sendai, Japan.
H
H
Hara
H
H
Onodera
H
H
Kato
K
K
Kogure
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D005849:Gerbillinae; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D018377:Neurotransmitter Agents; D011955:Receptors, Drug