Kenneth R. Brizzee

Age Differences in Short-Term Memory and Cell Loss in the Cortex of the Rat

Studies with human and animal subjects have indicated age declines in short-term memory and cell loss in the cortex. Cell loss has been estamated by descriptive nonautomated methods. Declines in short-term memory may be related to reduced learning, movtivation, motor capacity, or some combination of these factors. Passive-avoidance tests of memory minimize these factors. Direct correlational studies on learning and memory in relation to cell loss in the same subject are not feasible in man and they have not been reported previously in animals. The aims of this study were to examine age differences in learning and short-term passive-avoidance memory in relation to cell packing density in the visual cortex of the Fisher 344 rat. Cell counts were made with a computer-guided, automated, image-analyzing system (TAS, Leitz). The following observations were made: (1) significant age differences in 2- and 6-hour short-term passive-avoidance retention or memory between mature and senescent rats were related to nonsignificant age differences in original learning inferred from starting latencies, running time and running distance and (2) sd compared to mature rats were associated with significant differences in neuron but not glia-vascular cell density in area 17 in the presence of nonsignificant age differences in cortical depth and brain weight. Aims of further studies are to establish the role of cell loss from the hippocampus in loss of short-term spatial memory with age and to develop criteria for differential counting of small neurons, glia, endothelial cells and pericytes.

The ultrastructural morphology of the squirrel monkey area postrema.

SummaryExamination of the squirrel monkey (Saimiri sciureus) area postrema (AP) revealed this circumventricular organ to be primarily composed of two types of glial cells and a single type of neuronal element. No pattern of neuronal arrangement could be discerned, however, this cell type was frequently observed in close relation to the perivascular spaces. The neuronal elements, although slightly larger than the glial cells, were characteristically less electron dense. The neurons routinely displayed an infolded nuclear membrane, a single nucleolus and the normal complement of subcellular organelles. Synaptic terminals were numerous, and both axo-somatic and axo-dendritic varieties were observed with the latter being more numerous. Both clear-cored and dense-cored vesicles could be observed in the same ending. Unmyelinated neuronal processes were the predominant type within the interior of the AP, although myelinated processes were also regularly present.Non-neuronal elements within the AP resembled CNS astrocytes and were as numerous as the neuronal elements. This cell type appeared to envelope completely the vasculature and separated the parenchyma from the perivascular spaces. The ventricular surface of the AP was covered by modified ependyma which lacked kinocilia but frequently demonstrated microvillar projections. Opposed ependymal cell membranes showed interdigitations, and zonula adherens-type cell junctions connected the ependymal cells near the ventricular lumen. Two types of bulbous projections were observed in the ventricular lumen close to the ependymal surface.The most characteristic feature of the AP, however, was its vascularity. Perivascular spaces surrounding fenestrated capillaries contained fibroblasts and collagen. The vascular endothelium routinely demonstrated pinocytotic activity, and the basal lamina was prominent.

Muscarinic cholinergic receptors in area postrema and brainstem areas regulating emesis

Central cholinergic pathways modulate both the perception of excessive motion stimuli and the expression of motion sickness symptoms, such as nausea and vomiting. Specific brainstem areas which mediate motion-induced emesis include the area postrema (AP), vagal nuclear complex (VNC), reticular formation (RF) at the site of the vomiting center, and the vestibular complex (VC). In this report, histological studies indicated the cellular organization of brainstem structures mediating emesis was similar in bovine and squirrel monkey brain. The objective of this study was to characterize biochemical and pharmacological properties of muscarinic cholinergic receptors assayed by 3H-QNB binding in these regions of bovine brainstem. Scatchard analyses of specific 3H-QNB binding showed an uneven distribution of muscarinic receptors, with high densities of sites in VNC and AP, intermediate levels in RF and lowest receptor concentrations in VC. Dissociation constants for 3H-QNB, measured in saturation and kinetic experiments, were similar in all brainstem regions. The pharmacological potency of cholinergic agonists and antagonists was the same as reported for muscarinic receptors labeled in other brain areas or peripheral organs. Several drugs which potently inhibited 3H-QNB binding in bovine brainstem also exhibited antiemetic activity in a squirrel monkey model of motion-induced emesis. The antimotion sickness effects of these drugs may be due, in part, to their antagonism of muscarinic receptors in brainstem areas regulating emesis.

Depth distribution of lipofuscin pigment in cerebral cortex of albino rat

SummaryThe proportion of neuron somata occupied by lipofuscin pigments was determined at 20 relative depth levels throughout the depth of cerebral cortex (area 3) through the use of an integrating ocular and application of the Chalkley (1943) „hit” method.The proportion of the neuron soma volume occupied by autofluorescent granules was calculated from the above data. The highest (peak) values were observed in lamina Vb (23%-aged, 13%-middle age, and 6%-young adult). Mean values for the entire depth of cortex increased from 3% in 100 day rats to 6% in 400 days and 13% at 630–700 days. Theproportional increase in the relative volume of cell soma occupied by lipofuscin pigment from young adulthood to old age was greatest in lamina III, followed closely by lamina II.Ultrastructural studies of neurons in lamina V of cerebral cortical area 3 of young adult (150 day) and very aged (1200 day) albino rats revealed that electron-dense pigment bodies in neuron somata tended to increase in amount and size with increase in age of the animals. These changes were accompanied by changes in gross configurations and internal structure of the pigment bodies and a tendency to congregate in groups within the perikarya. Similar changes, although more variable, were observed in pigment accumulation within perineuronal glial cells.ZusammenfassungDas Verhältnis der lipofuscinpigmenthaltigen Nervenzelleiber wurde in 20 relativen Tiefenniveaus der Großhirnrinde (Area 3) der Albinoratte mittels eines Integrationsoculars und der Chalkleyschen Treffermethode (1943) bestimmt.Der Anteil des von autofluorescierenden Granula eingenommenen Nervenzellvolumens wurde aus den obigen Daten errechnet. Die höchsten (Spitzen)-Werte wurden in Lamina Vb beobachtet (23% bei alten, 13% bei mittelalten und 6% bei jungen erwachsenen Ratten). Die Mittelwerte für die gesamte Rindentiefe erhöhen sich von 3% bei 100 Tage alten Ratten auf 6% bei 400 Tage alten bis auf 13% bei 630–700 Tage alten Ratten. Der anteilsmäßige Zuwachs im Relativvolumen des von Lipofuscinpigment eingenommenen Zelleibes vom jungen Erwachsenen-Alter bis zu hohem Alter war in Lamina III am größten, knapp gefolgt von Lamina II.Ultrastrukturuntersuchungen der Nervenzellen in Lamina V der Area 3 der Großhirnrinde bei jungen erwachsenen Tieren (150 Tage) und sehr alten (1200 Tage) Albinoratten ergaben, daß die elektronendichten Pigmentkörperchen in den Nervenzelleibern an Zahl und Größe mit dem Alterszuwachs der Tiere zunahmen. Diese Veränderungen waren von solchen der äußeren Konfiguration und inneren Struktur der Pigmentkörperchen sowie der Tendenz zur Gruppenbildung innerhalb der Perikarya begleitet. Ähnliche, wenn auch mehr variable Veränderungen wurden bei der Pigmentanhäufung innerhalb der perineuronalen Gliazellen festgestellt.

Free radical theory of aging: Effect of dietary lipids on lipofuscin accumulation in the hippocampus of rats

The fatty acid composition of central nervous system lipids is largely independent of the dietary fat except for docosahexanoic acid (22:6ω3) and its precursors, mainly linolenic acid (18:3ω3). Ingestion of these lipids increases peroxidizability of neuronal phospholipids by displacing 22:5ω6 with 22:6ω3. Since lipofuscin (age pigment) is formed by oxidative polymerization of lipid and protein it seemed likely that increases in dietary 22: 6ω3 and/or peroxidizability of the dietary lipids might enhance lipofuscin accumulation. To evaluate these possibilities groups of male Charles River CD strain rats were fed a commercial diet, or semi-synthetic diets containing either 5%w (percent by weight) lard, 20%w olive oil, or 20%w safflower oil for periods up to 28 months of age; the amount of 22:6ω3 in lard is small, but considerably more than that of 22:6ω3 plus its precursors in olive oil or safflower oil.At 24 months of age the lipofuscin content of hippocampal neurons of rats fed the lard diet was significantly greater than for the control, olive oil or safflower oil groups; there was no significant difference between the latter two groups.Thus lipofuscin accumulation in hippocampal neurons was associated with increases in neuronal content of 22:6ω3 and not with the gross peroxidizability of the dietary lipid.

Neuron numbers and dendritic extent in normal aging and alzheimer's disease

Evidence is reviewed regarding neuron numbers and dendritic extent in normal aging in rodent, monkey and human brain and in Alzheimers disease (AD) in man. Neuron loss and change in dendritic extent appear to be regionally specific but not identical in rodents and primates. In AD there is excess neuron loss and dendritic regression in some but not all brain regions. Overlap between AD and control groups, however, is known to occur. Methods to assess dynamic morphology of the living brain may be superior to analysis of static, post-mortem brain structure in explaining functional deficits in AD and normal aging.

The Anti-Emetic Properties of 1-Sulpiride in a Ground-Based Model of Space Motion Sickness

L-sulpiride, at a dose of 4 mg/kg, essentially abolished motion-induced emesis in a group of 6 squirrel monkeys undergoing horizontal rotation at 25 rpm, a terrestrial model of space motion sickness (SMS). Extrapyramidal side effects were not observed. In the absence of the drug, the usual emetic response returned. In comparison while typical neuroleptics were also strongly anti-emetic, they produced a considerable degree of rigidity and akinesia.

Differential Accumulation of Lipofuscin Pigment in Cerebral Cortex of Rat

A comparison of the amount and distribution of lipofuscin pigment in neurons of cerebral cortex in prenatally X-irridiated (90 r) and control aged rats was carried out in areas 3 and 17. The proportio

The Aging Process in the Neuron

The neuron as the ultimate anatomical and physiological unit of the nervous system, and the archetype of postreplicative cells of the body, has perhaps received a greater amount of attention as a model for the study of aging processes than any other cell type. Additional interest in the neuron as a subject for aging studies stems from the view that that these elements, in strategic locations in the nervous system, may function as pacemakers, or the central control elements, of the “time clocks” of aging which may determine the onset and rate of senescence (1).