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D L Rosene

Publications and source records attributed to D L Rosene.

At least 19 recordsLinked to original sources
PubMed2004

Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex.

Executive system function, mediated largely by the prefrontal cortex (PFC), often declines significantly with normal aging in humans and non-human primates. The neural substrates of this decline are unknown, but age-related changes in the structural properties of PFC neurons could lead to altered synaptic signaling and ultimately to PFC dysfunction. The present study addressed this issue using whole-cell patch clamp assessment of excitatory and inhibitory postsynaptic currents (PSCs) in layer 2/3 pyramidal cells in in vitro slices of the PFC from behaviorally characterized young (< or =12 years old) and aged (> or =19 years old) rhesus monkeys. Behaviorally, aged monkeys were significantly impaired in performance on memory and executive system function tasks. Physiologically, the frequency of spontaneous glutamate receptor-mediated excitatory PSCs was significantly reduced in cells from aged monkeys, while the frequency of spontaneous GABAA receptor-mediated inhibitory PSCs was significantly increased. In contrast, there was no effect of age on the frequency, amplitude, rise time or decay time of action potential-independent miniature excitatory and inhibitory PSCs. The observed change in excitatory-inhibitory synaptic balance likely leads to significantly altered signaling properties of layer 2/3 pyramidal cells in the PFC with age.

Aging↗
PubMed2003

Hypertension-induced changes in monoamine receptors in the prefrontal cortex of rhesus monkeys.

Hypertension affects approximately 60 million people in the United States. Recent studies have demonstrated that hypertension may produce progressive changes in the CNS. The present study is focused on reports in the literature that hypertension may significantly alter neurotransmitter systems, particularly dopamine (DA) and norepinephrine (NE). To address this, DA and norepinephrine (NE) receptor binding was assessed in the prefrontal cortex (PFC) of 15 male rhesus monkeys using on-the-slide in vitro assays for the DA1, NE alpha1 and NE alpha2 receptors as well as for the DA and NE uptake transporters. Eight monkeys underwent surgical coarctation of the mid-thoracic aorta which produced sustained, untreated hypertension as defined by a systolic pressure above 150 mm Hg. Compared with normotensive controls, chronic, untreated hypertension produced a significant decrease in DA1 and NE alpha1 receptor binding and an increase in DA uptake (DAU) receptor binding in the prefrontal cortex. While the mechanisms by which untreated hypertension alters DA and NE receptors is not known, the use of this non-human primate model should provide the means to uncover neurobiological changes that occur with untreated hypertension.

Animals↗
PubMed2002

Birthdates and number of neurons in the serotonergic raphe nuclei in the rat with prenatal protein malnutrition.

The effect of prenatal protein deprivation on timing of neurogenesis and on number of neurons generated in the serotonergic dorsal (DR) and median raphe (MR) nuclei of the rat was studied. These neurons are of interest because their neurogenesis occurs during the period of malnutrition and their axonal projections participate in the earliest stages of brain development. In this study, dams were maintained on a 25% casein diet or a 6% casein diet 5 weeks prior to mating and throughout pregnancy. At birth, all pups were cross-fostered to dams on a 25% casein diet. Bromodeoxyuridine, a thymidine analog that is incorporated into nuclear deoxyribonucleic acid during the cell cycle synthetic phase, was used as a marker of neurogenesis. Bromodeoxyuridine was administered on either embryonic day 11, 12, 13 or 14. On postnatal day 30, serial sections of raphe nuclei were processed with bromodeoxyuridine immunocytochemistry to determine the number of raphe cells generated on each day and with Nissl stain to determine the total number of cells generated. There were no significant differences between the two diet groups in timing of generation or in total number of cells generated, indicating that neurogenesis of these early generated neurons appears unaffected by concomitant protein deprivation.

Animals↗
PubMed2000

Astrocytic hypertrophy and altered GFAP degradation with age in subcortical white matter of the rhesus monkey.

Reactive astrocytosis is a well known phenomenon that occurs in the normal aging process of the brain. While many studies indicate astrocytic hypertrophy and glial fibrillary acidic protein (GFAP) content increase with age in the hippocampal formation of certain animal models, it is unclear whether these findings are generalizable to the primate and to other areas of the brain. In this study, we quantitatively assessed age-related changes in astrocytic cell size and density in a rhesus monkey model of normal aging. By GFAP immunohistochemistry, we observed an increase in GFAP(+) cell size but not density in all subcortical white matter areas of the frontal, temporal, and parietal cortices. No significant increases in astrocyte hypertrophy were observed in any gray matter area examined. In addition, Western blotting experiments showed increases in total and degraded GFAP content with age, suggesting altered degradation and possibly production of GFAP occur with age.

Aging↗
PubMed2000

Chlordiazepoxide-induced spatial learning deficits: dose-dependent differences following prenatal malnutrition.

The sensitivity of prenatally protein-malnourished rats to the amnestic properties of the benzodiazepine (BZ) receptor agonist, chlordiazepoxide (CDP), was studied in the male offspring of rats provided with a protein-deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy. Rats were tested during acquisition of the submerged platform version of the Morris water maze task using three systemic doses of CDP (3.2, 5.6, and 7.5 mg/kg i.p.) at two ages (day 30 and day 90). At 30 days, prenatally malnourished rats showed less sensitivity to the amnestic effect of the 5.6-mg/kg dose when compared with well-nourished controls by displaying shorter swim paths during acquisition and a more selective search of the target quadrant upon removal of the platform (probe trial). At 90 days, prenatally malnourished rats again showed less sensitivity to CDP at a dose of 5.6 mg/kg, but more sensitivity to the 3.2-mg/kg dose (indicated on the probe trial). No obvious relationship was identified between the nutritional group differences in behavioral sensitivity to CDP at 90 days and their BZ receptor density in the hippocampus or medial septum. It can be concluded that prenatal malnutrition alters the amnestic response to CDP in a dose-dependent and developmentally specific manner, thus providing further support for functional changes within the GABAergic system subsequent to malnutrition.

Animals↗
PubMed2000

Serum amyloid A is present in the capillaries and microinfarcts of hypertensive monkey brain: an immunohistochemical study.

Serum amyloid A (SAA) is a major inducible acute phase protein characterized as a transient injury specific constituent of high density lipoprotein. We investigated whether the acute phase SAA (A-apoSAA), as a marker of inflammation, is present in the brain of monkeys with surgically induced hypertension of 39 months duration. Sections from brains of normotensive monkeys (systolic blood pressure < 124 mmHg) and hypertensive monkeys (systolic blood pressure > 185 mmHg) were processed for immunohistochemistry with a rabbit polyclonal antiserum to human A-apoSAA. We found that A-apoSAA was present in hypertensive but not in normotensive brain sections. Staining was localized to capillary endothelial cells and occasionally to the entire vessel wall of the prefrontal cortex. Staining was also observed in the capillaries and in medium size vessels of the corona radiata, the head of the caudate and, to a smaller extent, in the putamen. Additionally, the A-apoSAA was present in cells forming a circular configuration within microinfarcts. These findings suggest that high blood pressure in the brain can result in either local production of A-apoSAA in the capillaries and within microinfarcts or uptake of A-apoSAA from the blood

Animals↗
PubMed1999

Age-related decline in DHEAS is not related to cognitive impairment in aged monkeys.

To determine whether endogenous DHEAS level is related to cognitive performance in the rhesus monkey, we tested 9 young and 14 old monkeys on the acquisition and the 120 s delay condition of the delayed non-matching to sample and on the spatial delayed recognition span test. A single summary measure of cognitive ability, the cognitive performance index (CPI), was derived from these three tests. As expected, the mean level of DHEAS as well as the CPI declined with age. DHEAS level, however, was not significantly correlated with CPI, after controlling for the relationship of age to these two variables. Further, impaired and unimpaired aged monkeys did not differ in DHEAS level. These findings suggest that DHEAS is not independently associated with age-related cognitive decline in the rhesus monkey.

Aging↗
PubMed1999

Hippocampal formation lesions produce memory impairment in the rhesus monkey.

There is much debate over the role of temporal lobe structures in the ability to learn and retain new information. To further assess the contributions of the hippocampal formation (HF), five rhesus monkeys received stereotactically placed ibotenic acid lesions of this region without involvement of surrounding ventromedial temporal cortices. After surgery, the animals were trained on two recognition memory tasks: the Delayed Non-Match to Sample (DNMS) task, which tests the ability to remember specific trial unique stimuli, and the Delayed Recognition Span Task (DRST), which tests the ability to remember an increasing array of stimuli. Relative to normal control monkeys, those with HF lesions demonstrated significant impairments in both learning and memory stages of the DNMS task. Additionally, the HF group was significantly impaired on spatial, color, and object versions of the DRST. Contrary to suggestions that damage to the entorhinal and parahippocampal cortices is required to produce significant behavioral deficits in the monkey, these results demonstrate that selective damage to the HF is sufficient to produce impairments on tasks involving delayed recognition and memory load. This finding illustrates the importance of the HF in the acquisition and retention of new information.

Animals↗
PubMed1999

Spatial cognition in rhesus monkeys: male superiority declines with age.

Twelve young (4-7 years of age) and 14 old (20-27 years of age) male and female rhesus monkeys were tested on seven cognitive tasks. Males and females performed similarly on tasks of object memory and executive function, but young males outperformed young females on a spatial memory task (Delayed Recognition Span Test) that requires the identification of a new stimulus among an increasing array of serially presented stimuli. This superior level of spatial ability in young males declined sharply with age, so that old males did not perform significantly better than old females. These findings in the nonhuman primate suggest that biological rather than sociocultural factors underlie the sex differences in cognition and their diminution with age.

Aging↗
PubMed1999

Prenatal availability of choline alters the development of acetylcholinesterase in the rat hippocampus.

Choline (Ch) supplementation during embryonic days (ED) 12-17 enhances spatial and temporal memory in adult and aged rats, whereas prenatal Ch deficiency impairs attention performance and accelerates age-related declines in temporal processing. To characterize the neurochemical and neuroanatomical mechanisms that may mediate these behavioral effects in rats, we studied the development [postnatal days (PD) 1, 3, 7, 17, 27, 35, 90, and 26 months postnatally] of acetylcholinesterase (AChE) activity in hippocampus, neocortex and striatum as a function of prenatal Ch availability. We further measured the density of AChE-positive laminae (PD27 and PD90) and interneurons (PD20) in the hippocampus as a function of prenatal Ch availability. During ED11-ED17 pregnant Sprague-Dawley rats received a Ch-deficient, control or Ch-supplemented diet (average Ch intake 0, 1.3 and 4.6 mmol/kg/day, respectively). Prenatal Ch deficiency increased hippocampal AChE activity as compared to control animals in both males and females from the 2nd to 5th week postnatally. Moreover, prenatal Ch supplementation reduced hippocampal AChE activity as compared to control animals over the same developmental period. There was no effect of prenatal Ch status on either cortical or striatal AChE activity at any age measured, and by PD90 the effect of Ch on hippocampal AChE was no longer observed. In order to localize the early changes in hippocampal AChE activity anatomically, frozen coronal brain sections (PD20, PD27, PD90) were stained histochemically for AChE. Consistent with biochemical results, the AChE staining intensity was reduced in PD27 hippocampal laminae in the Ch-supplemented group and increased in the Ch-deficient group compared to control animals. There was no effect of the diet on hippocampal AChE staining intensity on PD90. In addition, the prenatal Ch availability was found to alter the size and density of AChE-positive PD20 interneurons. These results show that prenatal Ch availability has long-term consequences on the development of the hippocampal cholinergic system.

Acetylcholinesterase↗
PubMed1998

Organization of direct hippocampal efferent projections to the cerebral cortex of the rhesus monkey: projections from CA1, prosubiculum, and subiculum to the temporal lobe.

This study investigates direct hippocampal efferent projections to the temporal lobe of the rhesus monkey. Tritiated amino acid injections were placed into the hippocampal formation to identify terminal fields, and complementary fluorescent retrograde tracer injections were placed into the cortex to identify the cells of origin. Tritiated amino acid injections into CA1, prosubicular, or subicular subfields produced anterograde label over parts of the parahippocampal gyrus and temporal pole. Injections of fluorescent retrograde tracers demonstrated that these projections originate from longitudinal strips of neurons that occupy part of the CA1 subfield as well as from strips of neurons in adjacent prosubicular and subicular subfields. Thus, an injection into area TH of the posterior parahippocampal gyrus labeled neurons in a longitudinal strip of proximal CA1 (i.e., near CA2) as well as a strip in the subiculum; injections into areas TF, TL, 35, or Pro labeled neurons in a longitudinal strip of distal CA1 (i.e., near the prosubiculum) as well as one in the prosubiculum; and an injection into area TFO labeled neurons in a longitudinal strip in the middle of CA1. These strips of neurons extended longitudinally throughout the entire rostrocaudal length of the hippocampus. These results demonstrate that, in the monkey, CA1 projections to cortex arise topographically from longitudinally oriented strips of neurons that occupy only a part of the transverse extent of CA1 but that cover most of the anteroposterior extent of the hippocampus. Thus, in the monkey, CA1 is not a single uniform entity and may have a unique role as a source of direct hippocampal projections to the cerebral cortex.

Animals↗
PubMed1997

Morphology and electrophysiology of dentate granule cells in the rhesus monkey: comparison with the rat.

The morphologic and electrophysiologic properties of dentate granule cells in the young adult rhesus monkey (Macaca mulatta) were examined for the first time with whole-cell patch clamp recordings and intracellular biocytin filling in in vitro hippocampal slice preparations. Data from monkeys were compared with data generated in an identical manner from adult Sprague-Dawley rats. Intracellularly filled monkey and rat granule cells were identical in numerous morphologic parameters, including area of somata, total dendritic length, dendritic spread, segment number and length, and branching pattern. The single statistically significant difference in morphology was the vertical extent of the dendritic tree (distance from soma to fissure), which was 20% greater in the monkey. The passive membrane properties (resting membrane potential, input resistance, and membrane time constant) measured under current clamp conditions were virtually identical. The thresholds and amplitudes of action potentials were the same, but significant differences were seen in the kinetics of single action potentials. Monkey granule cell action potentials were significantly longer in duration (with slower rise and fall times) than action potentials in rat cells. These differences were likely due to a much smaller fast after hyperpolarization in the monkey as compared with the rat cells. Thus, with the exception of action potential properties, the principal finding of this study is that there is significant conservation of both form and function in dentate granule cells in these two species, despite the enormous phylogenetic separation. This suggests that granule cell properties may be extremely stable across diverse mammalian species.

Action Potentials↗
PubMed1997

Age-related neuronal loss in the nucleus centralis superior of the rhesus monkey.

The effect of age on the number of neurons in the nucleus centralis superior (NCS) was determined in 11 behaviorally tested rhesus monkeys of 7-32 years of age, There was a significant age-related decrease in both cell packing density and in the total number of neurons. This decrease in number of neurons appeared to effect two different populations of cell in the NCS, one of which corresponded in size to the serotonergic cells in this nucleus and the other to a smaller-sized cell. Comparisons of the changes in the cell packing density with behavioral testing, showed significant correlations with the overall test performance as well as with individual tests of memory function and of executive system functions. These findings suggest that neuronal loss in the NCS may play a significant role in mediating cognitive changes seen in normal aging.

Age Factors↗
PubMed1997

Lack of correlation between plaque burden and cognition in the aged monkey.

To assess whether amyloid plaque accumulation in the monkey brain can account for age-related cognitive impairment that begins at about 20 years of age, we measured plaque content in the brains of 14 rhesus monkeys aged 5-30 years. We used immunohistochemistry employing the monoclonal antibody 6E10, which is specific to amino acids 1-17 of the amyloid beta peptide to identify amyloid plaques in serial coronal sections of the forebrain. Amyloid plaques accumulate with age, starting at 25 years of age and escalating after 30 years. Until the age of 30, plaques are only found in a few monkeys and are relatively sparse. Results from our group and others show that plaque content and the proportion of individuals afflicted with amyloid plaques increase with age. Although both cognitive dysfunction and plaque content increase with age, amyloid plaque content does not correlate with the cognitive dysfunction observed in elderly monkeys since even in very old subjects some cognitively impaired animals have few amyloid plaques and others with abundant plaques show only minor cognitive impairments. In summary, amyloid plaques appear to accumulate significantly only in monkeys over 25 years of age but do not appear to be a causal factor in age-related cognitive decline of the normal aging rhesus monkey.

Aging↗
PubMed1997

Patterns of cognitive decline in aged rhesus monkeys.

Although cognitive decline has been well established as a consequence of aging in non-human primate models, the prevalence or frequency of impairment for specific age ranges has not been described. The first aim of this study was to estimate prevalence of cognitive impairment on each of the six tests of cognitive performance by comparing the performance of early-aged (19-23 years old), advanced-aged (24-28 years old), and oldest-aged (29+ years old) monkeys to that of young adults (< 15 years old). The second aim was to derive a single overall measure of cognitive performance to help classify behavioral function in our aged monkeys. Accordingly, we obtained performance measures for these age groups on six behavioral measures: (1) acquisition of the delayed non-matching-to-sample task (DNMS); (2) performance of the DNMS with a delay of 120 sec; (3) the spatial condition of the delayed recognition span test (DRST); (4) the color condition of the DRST; (5) spatial reversal learning; and (6) object reversal learning. Early-aged monkeys displayed prevalence rates of impairment significantly greater than zero on all tasks except the DRST-color. The highest prevalence of impairment was observed in this age group in a task measuring spatial memory (DRST). Significant trends toward progressively higher impairment rates in advanced-aged and oldest-aged monkeys were observed for DNMS-acquisition, DRST-color and spatial reversal learning tasks. A linear transformation of standardized scores on the six cognitive tests was derived by means of principal components analysis (PCA). The first PCA (PCA1) included data from 30 monkeys with available data on all six measures, and yielded a composite measure which declined linearly with increasing age (r = -0.74). A second PCA (PCA2) was performed on data from 53 monkeys for which three test scores (DNMS-acquisition, DNMS-120s delay, and DRST-spatial condition) were available. The composite score derived from this analysis was highly correlated (r = 0.93) with the composite score from PCA1, suggesting that a score based on only three tests may provide an adequate classification of global cognitive ability.

Aging↗
PubMed1996

Neurobiological bases of age-related cognitive decline in the rhesus monkey.

The rhesus monkey offers a useful model of normal human aging because when monkeys are tested on a battery of behavioral tasks that can also be used to evaluate cognition in humans, it is found that the monkeys undergo an age-related decline in several domains of cognitive function as do humans. In monkeys these changes begin at about 20 years of age. To determine what gives rise to this cognitive decline, we have examined several parameters in the brains of monkeys. Some parameters do not change with age. Examples of this are the numbers of neurons in the neocortex and hippocampal formation, and the numbers of synapses in the hippocampal formation. Changes in other parameters can be positively correlated with chronological age; examples of this are numbers of neuritic plaques, a decrease in the numbers of neurons in the striatally projecting pars compacta of the substantia nigra, and a decrease in the thickness of layer I in primary visual cortex. But the most interesting changes are those that correlate either with cognitive decline alone, or with both cognitive decline and chronological age. Among these are a breakdown in the integrity of myelin around axons, an overall reduction in the volume of white matter in the cerebral hemispheres, thinning of layer I in area 46 of prefrontal cortex, and decreases in the cell density in cortically projecting brain stem nuclei. To date then, our studies suggest that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer I and in the integrity of myelinated axons, rather than an age-related loss of cortical neurons or synapses, as has long been assumed.

Aging↗
PubMed1996

Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys.

In order to determine whether there are age-related changes in the supragranular layer of the dentate gyrus of the rhesus monkey, we examined this layer in monkeys 4-35 years of age, spanning the entire range of adulthood of this species. Electron microscopic analyses were conducted to determine whether there is an age-related change in the number of synapsing axon terminals, in the cross-sectional area of these terminals, or in the length of the postsynaptic density at the synaptic junction. Only asymmetrical synapses in the anterior dentate gyrus were evaluated. In a subset of our monkeys (n = 6, ages 4-31 years), we compared three different approaches to the estimation of synaptic density: (1) the conventional profile method, in which synapse numbers are expressed per unit area of the examined tissue section; (2) the empirical formula of Colonnier and Beaulieu for converting areal densities into number of synapses per unit volume, and (3) the 'disector' method, a stereological approach to the estimation of the number of synapses per unit volume that makes no assumption about the shape of the objects. Data are presented validating the small-fold method of estimating section thickness for the disector. The three methods were highly intercorrelated (rs approximately 0.89), and none of the methods revealed an age-related loss of synapses. Analysis of the thickness of the dentate gyrus molecular layer suggests that the reference volume in which these synapses were counted dose not change with age. In addition, the conventional profile method showed no age-related change in the number of axodendritic or axospinous synapses, the cross-sectional area of the synapsing terminals, or the length of the postsynaptic densities of synapses. Together, these data suggest a remarkable age-related preservation of synapses in the normal aging monkey.

Aging↗