Stereological Analysis of Neuron, Glial and Endothelial Cell Numbers in the Human Amygdaloid Complex

Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm3 and mean cell numbers (x106) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals’ age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions

Balanced Synaptic Input Shapes the Correlation between Neural Spike Trains

Stimulus properties, attention, and behavioral context influence correlations between the spike times produced by a pair of neurons. However, the biophysical mechanisms that modulate these correlations are poorly understood. With a combined theoretical and experimental approach, we show that the rate of balanced excitatory and inhibitory synaptic input modulates the magnitude and timescale of pairwise spike train correlation. High rate synaptic inputs promote spike time synchrony rather than long timescale spike rate correlations, while low rate synaptic inputs produce opposite results. This correlation shaping is due to a combination of enhanced high frequency input transfer and reduced firing rate gain in the high input rate state compared to the low state. Our study extends neural modulation from single neuron responses to population activity, a necessary step in understanding how the dynamics and processing of neural activity change across distinct brain states

Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Quantitative spectroscopic determination of hemoglobin concentration and saturation in a turbid medium: analysis of the effect of water absorption.

The contribution of water to the quantitative determination of hemoglobin concentration and saturation by near-infrared spectroscopy in turbid media was investigated. The study consisted of in vitro measurements of an aqueous suspension containing Liposyn, bovine blood, and yeast buffered at pH 7.2. The optical coefficients of the medium (μa∼0.03 to 0.08 cm-1, μ′s ∼ 6 cm-1 at wavelengths of 715 and 825 nm) were similar to those of biological tissue in the near-infrared, and the hemoglobin concentration was about 23 μM. It was possible to reversibly saturate and desaturate hemoglobin in the full range of 0 to 100% by flowing either oxygen or nitrogen through the suspension. In these experimental conditions, water absorption must be taken into account to obtain accurate oxyhemoglobin concentrations and low hemoglobin saturation values. By contrast, the water correction has a small effect on the determination of deoxyhemoglobin concentration and high hemoglobin saturation values. By extrapolating the result to physiological conditions, where water content is lower and hemoglobin content is higher than in the experimental conditions, it was concluded that water absorption should have a smaller effect on the determination of hemoglobin concentrations and saturation in tissues at the wavelengths used in this study. In particular, for hemoglobin concentrations larger than 100 μM, the water correction is less than 5% at saturation values higher than 50%. © 1997 Society of Photo-Optical Instrumentation Engineers

Quantitative spectroscopic determination of hemoglobin concentration and saturation in a turbid medium: analysis of the effect of water absorption.

The contribution of water to the quantitative determination of hemoglobin concentration and saturation by near-infrared spectroscopy in turbid media was investigated. The study consisted of in vitro measurements of an aqueous suspension containing Liposyn, bovine blood, and yeast buffered at pH 7.2. The optical coefficients of the medium (μa∼0.03 to 0.08 cm-1, μ′s ∼ 6 cm-1 at wavelengths of 715 and 825 nm) were similar to those of biological tissue in the near-infrared, and the hemoglobin concentration was about 23 μM. It was possible to reversibly saturate and desaturate hemoglobin in the full range of 0 to 100% by flowing either oxygen or nitrogen through the suspension. In these experimental conditions, water absorption must be taken into account to obtain accurate oxyhemoglobin concentrations and low hemoglobin saturation values. By contrast, the water correction has a small effect on the determination of deoxyhemoglobin concentration and high hemoglobin saturation values. By extrapolating the result to physiological conditions, where water content is lower and hemoglobin content is higher than in the experimental conditions, it was concluded that water absorption should have a smaller effect on the determination of hemoglobin concentrations and saturation in tissues at the wavelengths used in this study. In particular, for hemoglobin concentrations larger than 100 μM, the water correction is less than 5% at saturation values higher than 50%. © 1997 Society of Photo-Optical Instrumentation Engineers