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Alan Peters

Publications and source records attributed to Alan Peters.

At least 19 recordsLinked to original sources
PubMed2006

Maturational sequence of newly generated neurons in the dentate gyrus of the young adult rhesus monkey.

The generation of new neurons in the hippocampal dentate gyrus of adult mammals has been characterized in rodents, but the details of this process have not been described in the primate. Eleven young adult rhesus monkeys were given an injection of the DNA synthesis phase marker bromodeoxyuridine (BrdU) and killed at varying survival intervals (2 hours to 98 days). The immature neuronal marker TUC-4 (TOAD/Ulip/CRMP-4) was used to define three stages of morphological maturation. Stage I neurons had small somata and lacked dendrites. Stage II neurons had larger somata and short dendrites. Stage III neurons were similar in size to mature granule cells and had branching dendrites that extended into the molecular layer. Examination of TUC-4-positive immature neurons colabeled with BrdU indicated that stage I neurons first appeared 2 days after BrdU injection, stage II neurons at 14 days, and stage III neurons at 35 days. Electron microscopy of TUC-4-labeled cells showed that stage I cells had ultrastructural features of immature neurons, whereas stage III neurons were similar to mature granule cells and formed synapses in the molecular layer. This suggests that stage III neurons could potentially integrate into the circuitry of the dentate gyrus. This study shows that the maturational sequence for new neurons in the adult monkey is similar to that of the adult rodent; however, maturation takes a minimum of 5 weeks in the monkey, which is substantially longer than what has been reported in rodents.

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PubMed2006

Age-related molecular reorganization at the node of Ranvier.

In myelinated axons, action potential conduction is dependent on the discrete clustering of ion channels at specialized regions of the axon, termed nodes of Ranvier. This organization is controlled, at least in part, by the adherence of myelin sheaths to the axolemma in the adjacent region of the paranode. Age-related disruption in the integrity of internodal myelin sheaths is well described and includes splitting of myelin sheaths, redundant myelin, and fluctuations in biochemical constituents of myelin. These changes have been proposed to contribute to age-related cognitive decline; in previous studies of monkeys, myelin changes correlate with cognitive performance. In the present study, we hypothesize that age-dependent myelin breakdown results in concomitant disruption at sites of axoglial contact, in particular at the paranode, and that this disruption alters the molecular organization in this region. In aged monkey and rat optic nerves, immunolabeling for voltage-dependent potassium channels of the Shaker family (Kv1.2), normally localizing in the adjacent juxtaparanode, were mislocalized to the paranode. Similarly, immunolabeling for the paranodal marker caspr reveals irregular caspr-labeled paranodal profiles, suggesting that there may be age-related changes in paranodal structure. Ultrastructural analysis of paranodal segments from optic nerve of aged monkeys shows that, in a subset of myelinated axons with thick sheaths, some paranodal loops fail to contact the axolemma. Thus, age-dependent myelin alterations affect axonal protein localization and may be detrimental to maintenance of axonal conduction.

Aging↗
PubMed2006

Long-term effects of cage-cleaning frequency and bedding type on laboratory rat health, welfare, and handleability: a cross-laboratory study.

Cage-cleaning is necessary for a hygienic environment, but since rats communicate using scent, they might suffer if their cages are cleaned too frequently. Male rats (Sprague-Dawley and Wistar) were kept for five months across four animal units. Their cages were cleaned twice-weekly, weekly, or every two weeks, and contained either aspen woodchips or absorbent paper bedding. Aggression, injuries and general health, weight gain, chromodacryorrhoea (a stress-related Harderian gland secretion), handleability, and lung pathology were monitored, as was in-cage ammonia. Cleaning frequency had no clear impact on rat welfare, although frequent cleaning decreased ammonia concentrations and handleability, and non-aggressive skirmishing was highest in weekly cleaned rats. Surprisingly, bedding type did not affect ammonia, but all ammonia readings were unexpectedly low. However, rats kept on aspen had greater sneezing rates and lung pathology than those on paper bedding, but also had higher body weights. The results raise concerns about aspen bedding, which is relatively inert compared with other wood beddings, but nevertheless more harmful than paper. Animal unit significantly affected eight of the 11 variables tested, having interactive effects on five of them. The study also demonstrates the interactive effects of different animal units, casting doubt on the feasibility of standardization. We explored multiple variables of interest, so all findings require confirmation through further work. Nevertheless, cage-cleaning rates seem to affect socially housed male rats little, while bedding type has important effects on rat health.

Ammonia↗
PubMed2005

Light and electron microscopic immunohistochemical detection of bromodeoxyuridine-labeled cells in the brain: different fixation and processing protocols.

Bromodeoxyuridine (BrdU) immunohistochemistry is the method of choice for labeling newly generated cells in the brain. Most BrdU studies utilize paraformaldehyde-fixed brain tissue because of its compatibility with both BrdU and other immunohistochemical methods. However, stronger fixation is required for electron microscopic studies, and unfixed tissue is needed for biochemical and molecular studies. Because there are no systematic studies comparing the effects of different fixatives on BrdU immunohistochemistry in brain tissue, we compared BrdU immunohistochemical methods in brain tissue fixed with 4% paraformaldehyde, a mixed glutaraldehyde-paraformaldehyde fixative for electron microscopy, and unfixed tissue from brains perfused only with buffer and flash frozen. After optimizing immunostaining protocols, qualitative assessments of light microscopic diaminobenzidine labeling and of double-label immunofluorescence with confocal microscopy demonstrated excellent BrdU labeling in each of the three groups. Quantitative stereological assessment of the number of BrdU-labeled cells in rat dentate gyrus showed no significant difference in the number of labeled cells detected with each perfusion protocol. Additionally, we developed a protocol to visualize BrdU-labeled cells in the electron microscope with adequate preservation of fine structure in both rat and monkey brain.

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PubMed2004

Oligodendrocytes, their progenitors and other neuroglial cells in the aging primate cerebral cortex.

In a previous study it was found that with age there is an increase in the frequency of paranodal profiles of myelinated nerve fibers in the cerebral cortex of monkeys. This indicates that there is an increase in the number of internodal myelin segments, and raises the question of whether additional oligodendrocytes are necessary to generate the increased numbers of internodal myelin segments. The present study shows that in layer 4C beta of monkey primary visual cortex there is an age-related increase in the number of oligodendrocytes. When young (4-10 years of age) and old (25-35 years of age) monkeys are compared, the increase is found to be approximately 50%, and it begins in middle age (12-19 years old). It is also shown that although there is no increase in the population of astrocytes in layer 4C beta with age, there appears to be a slight increase in the frequency of microglial cells. As their numbers increase, oligodendrocytes in pairs, rows and groups become more common, which suggests that additional oligodendrocytes are being generated by cell division. Since there is little evidence that mature oligodendrocytes can divide, it is probable that the new oligodendrocytes are generated from progenitor cells which, as many studies have shown, can be labeled by antibodies to NG2, a chondroitin sulfate proteoglycan. By comparing the appearance of these NG2-labeled cells with cells encountered in thin sections of normally prepared tissue, it is shown that the NG2-positive cells have the features of neuroglial cells that were previously described as beta astrocytes.

Aging↗
PubMed2004

A fourth type of neuroglial cell in the adult central nervous system.

Labeling central nervous tissue from mature animals with antibodies to NG2 chondroitin sulfate proteoglycan reveals the existence of large numbers of NG2 positive cells, at least some of which are oligodendroglial progenitors. It is generally agreed that these cells differ from the classically defined neuroglia, since they are antigenetically different from astrocytes, oligodendrocytes, or microglial cells. Although the NG2 positive cells have been well characterized in light microscopic preparations, examination of the labeled cells by electron microscopy have not led to general agreement about their morphological features. The basic reason for this is that it is difficult to obtain good preservation of the fine structure of NG2 labeled neurons. Since these NG2 positive cells are abundant in the central nervous system, it was decided to examine routinely prepared tissue from the brains of mature monkeys and rats by electron microscopy to determine if there is a neuroglial cell type whose presence has been overlooked. It soon became evident that there is a fourth type of neuroglial cell. These cells have pale, irregular shaped nuclei with a thin rim of heterochromatin beneath the nuclear envelope, and they have pale cytoplasm. Superficially they resemble astrocytes, which is the probable reason why the presence of this fourth type of neuroglial cell has been largely overlooked. However, the fourth type of neuroglial cell, here referred to as a ss neuroglial cell, has no intermediate filaments in its cytoplasm, the mitochondria are thinner than those of astrocytes, centrioles are frequently encountered in their cytoplasm, and when they are adjacent to capillaries they are always separated from the basal membrane by an astrocytic processes.

Animals↗
PubMed2004

Sanford Louis Palay.

Explore the source record for details and available documents.

History, 20th Century↗
PubMed2003

Disrupted myelin and axon loss in the anterior commissure of the aged rhesus monkey.

This study assesses the effects of age on the composition of the anterior commissure of the rhesus monkey. The anterior commissures of nine young (5-10 years), five middle-aged (15-20 years), and eight old (25-35 years) monkeys were examined by light and electron microscopy. In all, 90-95% of the nerve fibers in the anterior commissure are myelinated. With age, the structure of the myelin sheaths of some nerve fibers is altered. Some of the axons also show signs of degeneration and this leads to a loss of nerve fibers. Thus, in young and the middle-aged monkeys the mean number of myelinated nerve fibers in the anterior commissure is 2.2 x 10(6), while in the old monkeys the mean is 1.2 x 10(6). Increasing age is correlated with a reduction in the number of myelinated nerve fibers in the anterior commissure, an increase in the frequency of structural alterations in myelin sheaths, and an increase in the frequency of occurrence of degenerating axons. However, the number of myelinated nerve fibers is the only variable that correlates with cognition: in monkeys 5-20 years of age the fewer the number of nerve fibers the poorer the cognitive performance, as measured by our Cognitive Impairment Index (CII). The most common neuroglial cells in the anterior commissure are oligodendrocytes. They account for 86% of all neuroglial cell profiles, while astrocytes account for 9%, and microglial cells for 5% of profiles. There is no apparent change with age in the total numbers of neuroglial cells, although as they age each of the neuroglial cell types acquires some inclusions in their cytoplasm. The data, together with those from previous studies, support the concept that in aging there is a ubiquitous loss of myelinated nerve fibers from the brain and that fiber loss is preceded by alterations in the structure of many of the myelin sheaths.

Aging↗
PubMed2003

Is there remyelination during aging of the primate central nervous system?

The effect of aging on myelin sheaths in the rhesus monkey was studied in the vertical bundles of nerve fibers that traverse monkey cerebral cortex in primary visual area 17 and prefrontal area 46. As shown previously, with age the internodes of many of these myelin sheaths show structural changes, the most common of which is an accumulation of electron-dense cytoplasm within some sheaths, a change which is considered to indicate that breakdown of myelin is taking place. Supporting the suggestion that myelin is breaking down with age, astrocytes in the cortices of old monkeys contain phagocytosed myelin and some of the inclusion bodies in astrocytes label with antibodies to myelin basic protein. There is also evidence that remyelination is taking place. Thus, we have found an increase in the frequency of profiles of paranodes when transverse sections of the nerve fibers are examined. The increase in paranodal frequency with age is 57% in area 17 and 90% in area 46. This increase cannot all be attributed to lengthening of paranodes with age, because in area 17 the 11% increase in mean paranodal length with age is insufficient to account for an age-related increase in paranodal profile frequency. Consequently, there must be an increase in the number of internodal lengths of myelin with age, as would occur if shorter lengths of myelin are produced by remyelination. In support of the proposal that remyelination is occurring, short internodal lengths of myelin have been found in the nerve bundles passing through the cortices of old monkeys and inappropriately thin sheaths occur around some axons. Both of these features are generally considered to be the hallmarks of remyelination. Consequently, it is proposed that in the aging cerebral cortex of the monkey there is some breakdown of internodes of myelin with subsequent remyelination that leads to the formation of some new and shorter internodal lengths of myelin.

Aging↗
PubMed2002

Effects of age on the glial cells in the rhesus monkey optic nerve.

The optic nerve is a circumscribed white matter tract consisting of myelinated nerve fibers and neuroglial cells. Previous work has shown that during normal aging in the rhesus monkey, many optic nerves lose some of their nerve fibers, and in all old optic nerves there are both myelin abnormalities and degenerating nerve fibers. The present study assesses how the neuroglial cell population of the optic nerve is affected by age. To address this question, optic nerves from young (4-10 years) and old (27-33 years) rhesus monkeys were examined by using both light and electron microscopy. It was found that with age the astrocytes, oligodendrocytes, and microglia all develop characteristic cytoplasmic inclusions. The astrocytes hypertrophy and fill space vacated by degenerated nerve fibers, and they often develop abundant glial filaments in their processes. Oligodendrocytes and microglial cells both become more numerous with age, and microglial cells often become engorged with phagocytosed debris. Some of the debris can be recognized as degenerating myelin, and in general, the greater the loss of nerve fibers, the more active the microglial cells become.

Aging↗
PubMed2002

Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey.

In the rhesus monkey, the myelin sheaths of nerve fibers in area 46 of prefrontal cortex and in splenium of the corpus callosum show age-related alterations in their structure. The alterations are of four basic types. Most common is splitting of the dense line of myelin sheaths to accommodate electron dense cytoplasm derived from the oligodendroglia. Less common are splits of the intraperiod line to form balloons or blisters that appear to contain fluid, the occurrence of sheaths with redundant myelin, and thick sheaths that are almost completely split so that one set of compact lamellae is surrounded by another set. But despite these alterations in the sheaths, few nerve fibers show axonal degeneration. To quantify the frequency of the age-related alterations in myelin, transversely sectioned nerve fibers from the splenium of the corpus callosum and from the vertical bundles of nerve fibers within area 46 were examined in electron photomicrographs. The material was taken from 19 monkeys, ranging between 5 and 35 years of age. It was found that the frequency of alterations in myelin sheaths from both locations correlates significantly with age. In area 46, the age-related alterations also significantly correlate (P < 0.001) with an overall assessment of impairment in cognition, i.e., the cognitive impairment index, displayed by individual monkeys. The correlation is also significant when only the old monkeys are considered as a group. A similar result was obtained previously in our examination of the effects of age on the myelin sheaths of nerve fibers in primary visual cortex (Peters et al. [2000] J Comp Neurol. 419:364-376). However, in the corpus callosum the myelin alterations correlate significantly with only one component of the cognitive impairment index, namely the delayed nonmatching to sample task with a 2-minute delay. It is proposed that age-related myelin alterations are ubiquitous and that the correlations between their frequency and impairments in cognition occur because the conduction velocity along the affected nerve fibers is reduced, so that the normal timing sequences within neuronal circuits break down.

Aging↗
PubMed2002

Structural changes in the normally aging cerebral cortex of primates.

During normal aging humans exhibit some cognitive decline, but it is difficult to determine the underlying causes of this decline, because information about cognitive status is rarely available and preservation of the brain is usually inadequate for detailed cytological examination. One solution to this problem is to use a nonhuman primate model, such as the rhesus monkey, which exhibits age-related cognitive decline similar to humans, and can be cognitively tested before the brains are preserved for detailed examination. It is now known that cognitive decline in human and nonhuman primates is not due to loss of cortical neurons and there is no correlation between the frequency of senile plaques and cognitive status. Indeed apart from layer 1, neurons of cerebral cortex show few signs of aging, although there may be some loss of synapses throughout cortex. In contrast, both microglia and astrocytes come to contain phagocytosed material, but its origin is unknown. There is also loss of white matter, which is accompanied by some breakdown of myelin sheaths and alterations in oligodendrocytes. It is suggested that the myelin changes alter conduction velocities along axons. This would alter timing in neuronal circuits, contributing to cognitive decline.

Aging↗
PubMed2002

Structural changes that occur during normal aging of primate cerebral hemispheres.

Human and non-human primates show cognitive decline during normal aging. Originally, the decline was attributed to a loss of cortical neurons, but recent studies have shown there is no significant cortical neuronal loss with age. Neurons acquire pigment, but the only other obvious changes are in layer 1 of neocortex. Layer 1 becomes thinner as apical tufts of pyramidal cells lose branches, as well as synapses, and at the same time the glial limiting membrane thickens. How dendrites and synapses in deep layers are affected by age is uncertain, but there are decreases in the levels of some neurotransmitters and receptors. Throughout the brain myelin sheaths show signs of breakdown. This may contribute to cognitive decline because it would cause a slowing of conduction along nerve fibers, disrupting the timing in neuronal circuits. Concomitantly, the myelin-forming oligodendrocytes develop swellings along their processes and gain dense inclusions. Microglial cells and astrocytes accumulate large amounts of phagocytosed material with age, although the origins of this material are not known.

Aging↗
PubMed2002

The effects of age on the cells in layer 1 of primate cerebral cortex.

Although there is significant thinning of layer 1 with age in both occipital area 17 and prefrontal area 46 of the rhesus monkey, there are no significant age-related changes in the numbers of neurons, astrocytes, or microglia and oligodendrocytes in this layer. A few profiles of degenerating neurons have been encountered in old monkeys, but they are uncommon. Some astrocytes undergo hypertrophy with age, as evidenced by the increased thickness of the glial limiting membrane, and throughout layer 1 the amount of filaments in the cytoplasm of both their cell bodies and processes increases. The astrocytes also come to contain phagocytic material in the old monkeys, as do the microglial cells. We have previously shown that in both areas 17 and 46 there is an age-related loss of synapses from layer 1 and a concomitant loss of dendritic branches from the apical tufts of pyramidal cells from layer 1. These may be the sources of the material phagocytosed by the astrocytes and microglial cells.

Aging↗
PubMedDate not supplied

Examining neocortical circuits: some background and facts.

The first definitive studies of where afferents to cerebral cortex terminate were made possible by the finding that as they degenerate axon terminals become electron dense. Gold toning of Golgi impregnated neurons allowed the postsynaptic targets of these afferents to be identified by electron microscopy and also allowed the termination sites of axons from a variety of types of cortical neurons to be ascertained, while the development of antibodies to GAD and to GABA made it possible to determine which types of cortical neurons are inhibitory. Subsequently the use of gold toned, Golgi impregnated material to examine neuronal connectivity was made redundant by the development of techniques that allowed the physiological properties of cortical neurons to be evaluated in neurons filled intracellularly with markers. Intracellular filling showed the axonal trees of cortical neurons are much more widespread than had been revealed by Golgi impregnations. As a result of numerous studies of the axons of identified neurons, we know a great deal about where most of the different types of neurons in cerebral cortex form their synapses, but on the other side of the picture there is a dearth of information about the origins of the inputs that specific types of cortical neurons receive. However, it is evident that each cortical neuron is the focus of input from many other neurons, and on the basis of the available data it is estimated that a single pyramidal cell in cortex receives its input from as many as 1,000 other excitatory neurons and as many as 75 inhibitory neurons.

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