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R W Verwer

Publications and source records attributed to R W Verwer.

At least 19 recordsLinked to original sources
PubMed2000

Decreased hippocampal metabolic activity in Alzheimer patients is not reflected in the immunoreactivity of cytochrome oxidase subunits.

In the present study we have compared histochemically determined cytochrome oxidase activity with the levels of immunocytochemically stained cytochrome oxidase subunits (CO II and CO IV) and ATP synthase in the human hippocampus in relation with Alzheimer's disease. Cytochrome oxidase activity was significantly reduced in all hippocampal areas of Alzheimer patients. The protein levels of subunits II and IV were not different between control subjects and Alzheimer patients. Additionally, it was observed that the active cytochrome oxidase is evenly distributed over both cell bodies and neuropil, while a relatively large pool of inactive enzyme or precursors is limited to the neuronal somata. Further, in Alzheimer patients the CO IV immunoreactivity decreased with age, whereas in control subjects it increased with age. Our results suggest that the assembly of cytochrome oxidase or the processing of its subunits may be impaired.

Aged↗
PubMed1998

The magnocellular neurons of the hypothalamo-neurohypophyseal system display remarkable neuropeptidergic phenotypes leading to novel insights in neuronal cell biology.

For decades the magnocellular neurons of the hypothalamo-neurophypophyseal system (HNS), in which either vasopressin or oxytocin are produced and released into the bloodstream, have been playing a pivotal role in fundamental discoveries in the nervous system. The primary structure of vasopressin and oxytocin was the first of all neuropeptides to be published, i.e., in the 1950s by the Nobel prize laureate Du Vigneaud. Moreover, many trend-setting discoveries have their origin in the HNS, which abundantly expresses vasopressin and oxytocin, clearly displays its function and is relatively easily to manipulate. Examples are the phenomenon of coexpression of neuropeptides, patch-clamping of nerve endings, axonal transport of RNA, neuroglia interactions and the behavioral effects. An extraordinarily intriguing example is the homozygous Brattleboro rat, which lacks vasopressin by a germ-line mutation, and has disclosed many of the fundamental characteristics of peptidergic neurons, and neurons in general. In this chapter we will discuss a few of them, in particular the recent data on mutations in vasopressin RNA. It is to be expected that the HNS will retain its informative role in the next decades.

Animals↗
PubMed1998

Reduced neuronal activity and reactivation in Alzheimer's disease.

1. Alzheimer's disease is a multifactorial disease in which age and APOE-epsilon 4 are important risk factors. Various mutations and even viral infections such as herpes simplex (Itzhaki et al., 1997) may play an additional role. 2. The neuropathological hallmarks of Alzheimer's disease (AD), i.e. amorphous plaques, neuritic plaques (NPs), pretangles, neurofibrillary tangles (NFT) and cell death are not part of a single pathogenetic cascade but are basically independent phenomena. 3. Pretangles can occur in neurons from which the metabolic rate is not altered. However, in brain areas where classical AD changes, i.e. NPs and NFTs, are present, such as the CA1 area of the hippocampus, the nucleus basalis of Meynert and the tuberomamillary nucleus, a decreased metabolic rate is found. Decreased metabolic rate appears to be an independent phenomenon in Alzheimer's disease. It is not induced by the presence of pretangles, NFT or NPs. 4. Decreased metabolic rate may precede cognitive impairment and is thus an early occurring hallmark of Alzheimer's disease, which, in principle, may be reversible. The observation that the administration of glucose or insulin enhances memory in Alzheimer patients also supports the view that Alzheimer's disease is basically a metabolic disease. Moreover, several observations indicate that activated neurons are better able to withstand aging and AD, a phenomenon paraphrased by us as "use it or lose it". It is, therefore, attractive to direct the development of therapeutic strategies towards restimulation of neuronal metabolic rate in order to improve cognition and other symptoms in Alzheimer's disease. A number of pharmacological and non-pharmacological studies support the concept that activation of the brain indeed has beneficial effects on several aspects of cognition and other central functions.

Aging↗
PubMed1997

Lack of translation of normal 7B2 mRNA levels in hypothalamic mutant vasopressin cells of the homozygous Brattleboro rat.

The homozygous Brattleboro rat (di/di) synthesizes a vasopressin (VP) precursor with an aberrant C-terminus, which causes a hypothalamic form of diabetes insipidus. The neuroendocrine polypeptide 7B2 is present in VP and oxytocin (OT) neurons of the supraoptic and paraventricular nucleus of the hypothalamus in wild type rats. However, in the di/di rat 7B2 immunoreactivity is absent in the VP cell population, whereas 7B2 levels within the OT cells are unaffected. Remarkably, there is no obvious difference in 7B2 transcript levels between VP and OT neurons in the di/di rat hypothalamus. This study shows that the presence of mRNA does not automatically result in the subsequent synthesis of its protein. Cellular mechanisms underlying this discrepancy are discussed.

Animals↗
PubMed1997

Collateral projections from the rat hippocampal formation to the lateral and medial prefrontal cortex.

Projections from the hippocampal formation to the medial prefrontal cortex are well known. In this report we used two retrogradely transported tracers to show that a small but significant subpopulation of pyramidal neurons in area CA1 and subiculum of the hippocampal formation projects to the lateral prefrontal cortex. About half of these neurons also possess collateral projections to the medial prefrontal cortex. The neurons projecting only to the lateral PFC are found in the intermediate hippocampal formation and in the most ventral part of the temporal subdivision. On the other hand, most of the neurons projecting to the medial prefrontal cortex only are present in the temporal and ventral intermediate hippocampal formation, and their number decreases in the dorsal intermediate subdivision. The distribution of neurons having collateral projections is comparable to that of neurons projecting to the medial prefrontal cortex only. In view of proposed functional differences between the septal one-third and the temporal two-third of the hippocampal formation, it is of interest that the neurons projecting to the prefrontal cortex are only present in the temporal two-thirds.

Amidines↗
PubMed1997

Spatial delayed alternation of rats in a T-maze: effects of neurotoxic lesions of the medial prefrontal cortex and of T-maze rotations.

The medial prefrontal cortex (mPFC) is usually considered to be a brain area important for working memory processes. In rats this statement is evidenced by their diminished performance in delay-type tasks following mPFC damage, notably in spatial delayed alternation (SDA) in a T-maze. This study has addressed two questions. First, to examine whether the functional deficiency in SDA, observed in rats with (usually large) mPFC damage, can be ascribed to an anatomically defined subarea of mPFC, the dorsal anterior cingulate area (ACd). Small, bilateral, NMDA-induced lesions were made, restricted to the dorsal part of mPFC. The performance of such animals in a T-maze paradigm, using delays of 0 and 15 s, was compared with sham-operated animals. Although these small lesions resulted in an increased number of perseverative errors, this effect was not delay-dependent, and, moreover, by the end of the training group differences had disappeared. The second aim was to study whether or not spatial (extra-maze) cues are important for the performance of this task. This was achieved by subjecting the well-trained sham-operated animals to a series of systematic trial-to-trial variations in the position of the maze in the experimental room. These spatial manipulations severely impaired the performance of the SDA task, indicating that extra-maze information is required to solve this task. In animals with ACd lesions, subjected to the same manipulations, the deficiency was comparable to that of the sham-operated animals.

Animals↗
PubMed1996

Postnatal development of amygdaloid projections to the prefrontal cortex in the rat studied with retrograde and anterograde tracers.

The prefrontal cortex (PFC) and the amygdala are involved in a number of common functions, such as emotional and social behavior, stress, visceral functions, ingestive behavior, self-stimulation, and certain aspects of learning and memory. The amygdala massively projects to the PFC and may play a role in the developmental plasticity reported for several of these functions. We have studied the normal postnatal development of the amygdaloid projections to the rat prefrontal cortex by using the retrogradely transported fluorescent dye fast blue and the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Shortly after birth some fibers were observed in the frontal pole of the rat brain. These fibers were scattered throughout all prefrontal cortical areas. The majority of the amygdaloid cells contributing to this pattern at that stage of development were located in the anterior and ventral basolateral nuclei, whereas a minority were located in the posterior basolateral nucleus. The transition from a diffuse fiber distribution to a characteristic bilaminar pattern occurred around postnatal day 12 in the lateral and rostral medial PFC. The PHA-L injections confirmed the existence of a topographical organization of the amygdalo-prefrontocortical projections. Our observations suggest that the development of amygdala innervation of the PFC parallels the emergence of PFC cytoarchitectural organization.

Aging↗
PubMed1994

Age-related increase in the total number of corticotropin-releasing hormone neurons in the human paraventricular nucleus in controls and Alzheimer's disease: comparison of the disector with an unfolding method.

It has been hypothesized that the corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN) become hyperactive with age, and even more so in Alzheimer's disease. This hyperactivity could be due to an increased production of CRH per neuron, or an increased number of PVN neurons producing CRH, or both. As a first step in elucidating which of these biological mechanisms might be operative, we have estimated the absolute number of CRH immunoreactive neurons in the PVN of 10 human control subjects between 36 and 91 years of age and 10 Alzheimer patients between 40 and 97 years of age. CRH neurons were immunocytochemically detected in 6 microns paraffin sections with the aid of a highly specific monoclonal antibody to CRH. The antibody signal was amplified by the biotin-streptavidin and alkaline phosphatase methods. The absolute number of CRH neurons in the PVN was obtained by multiplying the number of CRH neurons in a unit volume (NV) by the total volume of the PVN. Two different methods were used to estimate the NV: an unfolding method and a disector method (about three times more time-consuming). Compared to the disector, the unfolding method consistently yielded a lower cell number for all patients by 38% (+/- 2.8%; mean +/- SEM). However, both methods yielded an increase in the absolute number of CRH neurons in control and Alzheimer patients with age. No statistically significant difference in the absolute number of CRH neurons was found between control and Alzheimer patients with both methods. The age-dependent increase in the absolute number of CRH neurons within the PVN of both control and Alzheimer patients is interpreted as a sign of activation of the CRH neurons with age.

Aged↗
PubMed1993

Efficient and unbiased estimation of volume and area of tissue components and cell number in gingival biopsies.

Recently, the methodology for volume and cell number estimation from sectioned tissue has undergone rapid progress. To date there are no indications in the literature that investigators in periodontal research are aware of this progress, published mainly in the disciplines of stereology and morphometry. This is unfortunate, as these developments could be profitably exploited in periodontal pathology. In this review we discuss the dangers of some currently used quantitative methods and indicate how simple unbiased methods together with an appropriate systematic sampling scheme lead to an efficient estimation of cell number and volume of tissue or tissue components.

Bias↗
PubMed1992

Tree asymmetry--a sensitive and practical measure for binary topological trees.

The topological structure of a binary tree is characterized by a measure called tree asymmetry, defined as the mean value of the asymmetry of its partitions. The statistical properties of this tree-asymmetry measure have been studied using a growth model for binary trees. The tree-asymmetry measure appears to be sensitive for topological differences and the tree-asymmetry expectation for the growth model that we used appears to be almost independent of the size of the trees. These properties and the simple definition make the measure suitable for practical use, for instance for characterizing, comparing and interpreting sets of branching patterns. Examples are given of the analysis of three sets of neuronal branching patterns. It is shown that the variance in tree-asymmetry values for these observed branching patterns corresponds perfectly with the variance predicted by the used growth model.

Animals↗
PubMed1990

Analysis of binary trees when occasional multifurcations can be considered as aggregates of bifurcations.

The geometrical properties of neurons are important for the way they function within neural circuits. The arborescent processes of neurons that are necessary for the transmission of the information are formed by branching and elongation of segments. In studies that model the outgrowth the tree structures have generally been considered as binary. However, multifurcations do occur. It will be shown that if the multifurcations can be considered as aggregates of bifurcations they may be included in the topological analysis of neuronal branching patterns.

Animals↗
PubMed1989

Organization of projections from the mediodorsal nucleus of the thalamus to the basolateral complex of the amygdala in the rat.

Mediodorsal thalamic (MD) projections to the basolateral amygdaloid complex of the rat were investigated with the anterograde neuronal tracer, Phaseolus vulgaris-leucoagglutinin. Iontophoretic injections were made in distinct subdivisions of the rostral and caudal part of the MD. Both the medial and lateral division of the MD showed a projection to the basolateral complex and there appears to be a topographical organization of the innervation in the rostrocaudal direction: the rostral and caudal part of the MD project to respectively the mid-rostrocaudal and rostral part of the basolateral complex.

Amygdala↗
PubMed1986

Application of growth models to the topology of neuronal branching patterns.

The variation in topological structure of branching patterns may contain essential information with respect to the way these branching patterns have grown. For the understanding of how growth modes finally result in a particular variety in topological patterns, model studies may provide indispensible tools. These studies imply the mathematical formulation of growth models and the development of statistical procedures to compare model predictions with observed data. Recent literature shows two main approached in these model studies, viz. subtree partition analysis (SPA) and vertex analysis. This paper will briefly review the current status with respect to SPA and will apply the model approach to sets of dendritic trees taken from pyramidal, multipolar non-pyramidal and from Purkinje cells. The results show that the topological properties of many dendrites are not in agreement with the hypothesis of random terminal growth and that substantial branching of intermediate segments and/or branching dependent of the position of segments in the tree (topological distance from the cell body) must be assumed. Only two parameters are required to incorporate these assumptions in the model. In all cases up to now it is possible to find parameter values such that the model predictions of topological properties are in agreement with the observations.

Animals↗
PubMed1986

Descriptive and comparative analysis of geometrical properties of neuronal tree structures.

The morphology of neurons is an important factor for the identification and the study of the changes that occur in the nervous system during development or as a result of disease or an experimental treatment. A number of methods to describe the topological aspects of neuronal morphology is discussed. Furthermore it is illustrated how different groups of neurons can be compared. Although both topological and metrical aspects are considered in the comparative sections emphasis is put on counting instead of measuring. Our intention is to present quick and easy methods that are applicable to camera lucida drawings.

Animals↗
PubMed1986

Alzheimer's disease: maintenance of neuronal and synaptic densities in frontal cortical layers II and III.

Neuronal loss and alterations of the cortical neuropil were previously described on necropsic material from patients with senile dementia of the Alzheimer type, and the results compared to age-matched case controls. In frontal cortex biopsic material from our patients with Alzheimer's disease, the numerical densities of neurons and synapses were not significantly different from controls, indicating that changes in the highest cognitive functions might not depend on a generalized loss of neurons and synapses and that quantitative morphological differences may exist between Alzheimer's disease and senile dementia of the Alzheimer type.

Alzheimer Disease↗
PubMed1985

The vasopressin and oxytocin neurons in the human supraoptic and paraventricular nucleus; changes with aging and in senile dementia.

The neuropeptides vasopressin (AVP) and oxytocin (OXT) are supposed to be involved not only in peripheral functions (e.g. diuresis, labour and lactation) but also in central processes that are frequently disturbed during aging and senile dementia (e.g. fluid and electrolyte homeostasis and cognitive functions). A concomitant decrease in activity of the hypothalamo-neurohypophyseal system (HNS) with aging has been postulated in the literature, but has not yet been established. In order to investigate possible age-related changes in the human HNS, immunocytochemically identified AVP and OXT neurons in the paraventricular and supraoptic nucleus (PVN and SON) were analysed morphometrically in subjects from 10 to 93 years of age, including patients with senile dementia of the Alzheimer type (SDAT). Cell size was used as a parameter for peptide production. Mean profile area of OXT cells did not show any significant changes with increasing age. Mean profile area of AVP cells, however, showed an initial decrease up to the sixth decade of life, after which a gradual increase was observed. Size of AVP and OXT cell nuclei did not change significantly with aging. Observations in brains from patients with SDAT were within the range for their age group. The present results do not support degeneration or diminished function of the HNS in senescence or SDAT, as generally presumed in the literature, but suggest an activation of AVP cells after 80 years of age. The activation of AVP cells in senescence is in accordance with previous findings in the aged Wistar rat.

Adolescent↗