Synapse Counts Research Articles

Cognitive Reserve Index questionnaire (CRIq): a new instrument for measuring cognitive reserve.

The concept of "reserve" has been used to explain the difference between individuals in their capacity to cope with or compensate for pathology. Brain reserve refers to structural aspects of the brain, such as brain size and synapse count. Cognitive reserve is the ability to optimize and maximize performance through two mechanisms: recruitment of brain networks, and/or compensation by alternative cognitive strategies. The aim of the present research was to devise an instrument for comprehensive assessment and measurement of the quantity of cognitive reserve accumulated by individuals throughout their lifespan. A new approach using the Cognitive Reserve Index questionnaire (CRIq) was developed and tested in a sample of 588 healthy individuals, from 18 to 102 years old, stratified by age (Young, Adults, Elderly) and gender. The CRIq includes demographic data and items grouped into three sections: education, working activity and leisure time, each of which returns a subscore. The WAIS Vocabulary test and TIB were also administered. The main descriptive features and some inferential results are described. Intelligence was only moderately correlated with cognitive reserve, stressing the distinction between these two concepts. Age and gender significantly affected CRIq scores, whereas no effect emerged from their interaction. Adults showed a higher score than Young and Elderly. This study provides a new instrument for a standardized measure of the cognitive reserve accumulated by individuals through their lifespan. The potential use of the CRIq in both experimental research and clinical practice is discussed.

Analogical Mapping with Sparse Distributed Memory: A Simple Model that Learns to Generalize from Examples

We present a computational model for the analogical mapping of compositional structures that combines two existing ideas known as holistic mapping vectors and sparse distributed memory. The model enables integration of structural and semantic constraints when learning mappings of the type \(x_i \rightarrow y_i\) and computing analogies \(x_j \rightarrow y_j\) for novel inputs x j . The model has a one-shot learning process, is randomly initialized, and has three exogenous parameters: the dimensionality \(\mathcal{D}\) of representations, the memory size S, and the probability χ for activation of the memory. After learning three examples, the model generalizes correctly to novel examples. We find minima in the probability of generalization error for certain values of χ, S, and the number of different mapping examples learned. These results indicate that the optimal size of the memory scales with the number of different mapping examples learned and that the sparseness of the memory is important. The optimal dimensionality of binary representations is of the order 104, which is consistent with a known analytical estimate and the synapse count for most cortical neurons. We demonstrate that the model can learn analogical mappings of generic two-place relationships, and we calculate the error probabilities for recall and generalization.

A computational study on the spatial correlation of granule cell firing in the cerebellar cortex

The cerebellum, also known as small brain, is a special region of the brain and plays critical roles in motor control. The granular layer, which harbors more than 95% of the cerebellar neurons (and more than 50% of the cells in the whole brain), is the input layer of the cerebellum, including two main neuron types: granule cells (GrCs) and Golgi cells (GoCs). From a functional perspective, the cerebral granular layer is responsible for receiving the mossy fiber (MF) inputs originally from sensory systems, cerebral cortex and spinal cord. These MF signals are then transformed and sent to the molecular layer, and eventually the Purkinje cells, to be further integrated to fine tune motor activities. Accordingly, elucidating the spatial/temporal dynamics of the granular layer is fundamental to understand the overall signal processing in the cerebellum. However, there remain many dynamical enigmas at the level of input integration relating to the spatial-temporal integration potentialities. In order to identify them, we built a large-scale 3D network model of the granular layer. The model (in NEURON) has dimensions 1 × 1 × 0.2 mm3, and contains both GrCs and GoCs with realistic cell and synapse counts, and has connectivity tightly constrained by anatomical literature [1]. Both cells receive excitatory inputs from MFs, and had their dynamics modeled according to detailed models, published in [2,3]. In the network, the GrCs (single-compartment) excited GoCs (multi-compartment) via parallel fibers. GoCs were the only source of inhibition for their surrounding GrCs. There was no connection between different GrCs, and gap junction coupling between GoCs was not considered. In this poster, we will present results on the properties of the spread of activity in the granular layer. In addition, we will discuss how the dynamical properties of MF inputs influence the spatial correlation of granule cell firing in the cerebellar cortex. Our results indicate that (1) the spatial correlation of granule cell firing is rather local, and (2) displays very short transient, and (3) exhibits a level of anisotropy. We hope that this work will contribute not only to the basic understanding of the spatial dynamics of the granule layer, but also to the capabilities of the cerebellum to integrate multimodal input.

ANALYSIS OF STRUCTURAL PLASTICITY IN THE HONEY BEE BRAIN USING THE CAVALIERI ESTIMATOR OF VOLUME AND THE DISECTOR METHOD

The antennal lobe of the worker honey bee has been used as a model system to address the origins of structural plasticity in the central nervous system. A combination of light and electron microscopy was used to determine total synapse number within an easily identifiable sub-unit of the antennal lobe neuropil, the T4-2(1) glomerulus. The Cavalieri method was applied at the light microscope level to determine a reference volume (Vref) of this glomerulus. Using transmission electron microscopy, the physical disector was used to determine synaptic density (Nv) within the T4-2(1) glomerulus. An estimate of the total synapse number N(syn) was determined by; N(syn) = V(ref) Nv. Newly emerged, 4-day old,10-day old and forager-aged bees were analysed. Results showed that despite a significant increase in T4-2(1) volume with age, the total number of synapses in this glomerulus did not show a corresponding increase. Disturbingly, it is possible that huge variances within age groups, due to one or two outlying data points, could be masking the true trend of synapse number. This variance, the heterogeneous distribution of synapses within this glomerulus and the problems associated with reproducibility of synapse counts are discussed.

Calcium-Dependent Synaptic Vesicle Trafficking Underlies Indefatigable Release at the Hair Cell Afferent Fiber Synapse

Sensory hair cell ribbon synapses respond to gradedstimulation in a linear, indefatigable manner, requiring that vesicle trafficking to synapses be rapid and nonrate-limiting. Real-time monitoring of vesicle fusion identified two release components. The first was saturable with both release rate and magnitude varying linearly with Ca(2+), however the magnitude was too small to account for sustained afferent firing rates. A second superlinear release component required recruitment, in a Ca(2+)-dependent manner, of vesicles not in the immediate vicinity of the synapse. The superlinear component had a constant rate with its onset varying with Ca(2+) load. High-speed Ca(2+) imaging revealed a nonlinear increase in internal Ca(2+) correlating with the superlinear capacitance change, implicating release of stored Ca(2+) in driving vesicle recruitment. These data, supported by a mass action model, suggest sustained release at hair cell afferent fiber synapse is dictated by Ca(2+)-dependent vesicle recruitment from a reserve pool.

Kognitive Reservekapazität und ihre Bedeutung für Auftreten und Verlauf der Demenz

Progressive brain damage is undoubtedly the main cause of clinical symptoms of dementia in neurodegenerative disorders such as Alzheimer's disease. However, the association between brain damage and cognitive symptoms is not linear. Certain interindividual differences such as a good school education or a greater brain volume are associated with a higher resilience against brain damage that is usually referred to as cognitive reserve (CR). Individuals with high CR have a diminished risk for dementia and both active and passive concepts for this phenomenon are discussed. In the concept of passive CR, peculiarities of brain structure such as higher synapse or neuron counts are regarded as buffers against brain damage. Symptoms of dementia do not occur until a certain threshold of damage is passed. In addition to the passive concepts, active mechanisms are also discussed that are associated with the ability to maintain a certain level of cognitive performance in the face of progressive neurodegeneration for a longer period. In subjects with healthy cognitive function, these active mechanisms contribute to the adaptation of brain activity when task difficulty level is increased. Confronted with progressive neurodegeneration, these active mechanisms help to compensate for brain damage. Individuals with higher CR show more efficient activation for solving the same task, which helps them to preserve normal levels of cognitive performance for a longer period.

Initial loss but later excess of GABAergic synapses with dentate granule cells in a rat model of temporal lobe epilepsy

Many patients with temporal lobe epilepsy display neuron loss in the dentate gyrus. One potential epileptogenic mechanism is loss of GABAergic interneurons and inhibitory synapses with granule cells. Stereological techniques were used to estimate numbers of gephyrin-positive punctae in the dentate gyrus, which were reduced short-term (5 days after pilocarpine-induced status epilepticus) but later rebounded beyond controls in epileptic rats. Stereological techniques were used to estimate numbers of synapses in electron micrographs of serial sections processed for postembedding GABA-immunoreactivity. Adjacent sections were used to estimate numbers of granule cells and glutamic acid decarboxylase-positive neurons per dentate gyrus. GABAergic neurons were reduced to 70% of control levels short-term, where they remained in epileptic rats. Integrating synapse and cell counts yielded average numbers of GABAergic synapses per granule cell, which decreased short-term and rebounded in epileptic animals beyond control levels. Axo-shaft and axo-spinous GABAergic synapse numbers in the outer molecular layer changed most. These findings suggest interneuron loss initially reduces numbers of GABAergic synapses with granule cells, but later, synaptogenesis by surviving interneurons overshoots control levels. In contrast, the average number of excitatory synapses per granule cell decreased short-term but recovered only toward control levels, although in epileptic rats excitatory synapses in the inner molecular layer were larger than in controls. These findings reveal a relative excess of GABAergic synapses and suggest that reports of reduced functional inhibitory synaptic input to granule cells in epilepsy might be attributable not to fewer but instead to abundant but dysfunctional GABAergic synapses.

Sprouting interneurons in mushroom bodies of adult cricket brains

In crickets, neurogenesis persists throughout adulthood for certain local brain interneurons, the Kenyon cells in the mushroom bodies, which represent a prominent compartment for sensory integration, learning, and memory. Several classes of these neurons originate from a perikaryal layer, which includes a cluster of neuroblasts, surrounded by somata that provide the mushroom body's columnar neuropil. We describe the form, distribution, and cytology of Kenyon cell groups in the process of generation and growth in comparison to developed parts of the mushroom bodies in adult crickets of the species Gryllus bimaculatus. A subset of growing Kenyon cells with sprouting processes has been distinguished from adjacent Kenyon cells by its prominent f-actin labelling. Growth cone-like elements are detected in the perikaryal layer and in their associated sprouting fiber bundles. Sprouting fibers distant from the perikarya contain ribosomes and rough endoplasmic reticulum not found in the dendritic processes of the calyx. A core of sprouting Kenyon cell processes is devoid of synapses and is not invaded by extrinsic neuronal elements. Measurements of fiber cross-sections and counts of synapses and organelles suggest a continuous gradient of growth and maturation leading from the core of added new processes out to the periphery of mature Kenyon cell fiber groups. Our results are discussed in the context of Kenyon cell classification, growth dynamics, axonal fiber maturation, and function.

The β-Propensity of Tau Determines Aggregation and Synaptic Loss in Inducible Mouse Models of Tauopathy

Neurofibrillary lesions are characteristic for a group of human diseases, named tauopathies, which are characterized by prominent intracellular accumulations of abnormal filaments formed by the microtubule-associated protein Tau. The tauopathies are accompanied by abnormal changes in Tau protein, including pathological conformation, somatodendritic mislocalization, hyperphosphorylation, and aggregation, whose interdependence is not well understood. To address these issues we have created transgenic mouse lines in which different variants of full-length Tau are expressed in a regulatable fashion, allowing one to switch the expression on and off at defined time points. The Tau variants differ by small mutations in the hexapeptide motifs that control the ability of Tau to adopt a beta-structure conformation and hence to aggregate. The "pro-aggregation" mutant DeltaK280, derived from one of the mutations observed in frontotemporal dementias, aggregates avidly in vitro, whereas the "anti-aggregation" mutant DeltaK280/PP cannot aggregate because of two beta-breaking prolines. In the transgenic mice, the pro-aggregation Tau induces a pathological conformation and pre-tangle aggregation, even at low expression levels, the anti-aggregation mutant does not. This illustrates that abnormal aggregation is primarily controlled by the molecular structure of Tau in vitro and in the organism. Both variants of Tau become mislocalized and hyperphosphorylated independently of aggregation, suggesting that localization and phosphorylation are mainly a consequence of increased concentration. These pathological changes are reversible when the expression of Tau is switched off. The pro-aggregation Tau causes a strong reduction in spine synapses.

Stereological Analysis Reveals Striking Differences in the Structural Plasticity of Two Readily Identifiable Glomeruli in the Antennal Lobes of the Adult Worker Honeybee

The primary antennal sensory centers (antennal lobes) in the brain of the honeybee are highly compartmentalized into discrete spheres of synaptic neuropil called glomeruli, many of which can be identified according to their predictable size and location. Glomeruli undergo significant changes in volume during the lifetime of the adult worker bee, at least some of which are activity dependent. This study tests the commonly expressed assumption that increases in neuropil volume are accompanied by an underlying increase in the number of synapses present in the tissue. A combination of light and electron microscopy was used to determine total synapse number within two glomeruli, T1-44 and T4-2(1). The Cavalieri direct estimator of volume was applied to 1.5 microm sections of resin-embedded brains. Selected sections were then re-embedded and prepared for transmission electron microscopy. Synapse densities were determined using the physical disector method on electron micrographs. Synapse density and glomerulus volume were combined to give an unbiased estimate of the total number of synapses. In glomerulus T1-44, a significant increase in volume was accompanied by a significant increase in the total number of synapses. In contrast, synapse counts in T4-2(1) remained unchanged, despite a significant increase in the volume of this glomerulus. These results demonstrate that synapse proliferation in antennal lobes of the adult worker bee is highly site specific. Although volumetric changes and changes in synapse number both contribute to the structural plasticity of the antennal lobes, these two components of plasticity appear to be independent processes.

Weightlessness during spaceflight results in enhanced synapse formation in a fish brain vestibular nucleus

Synapse counts were undertaken by conventional electron microscopy in primary vestibular integration centers, (i.e. nucleus descendens and nucleus magnocellularis of the brainstem area octavolateralis) and in the diencephalic visual nucleus corticalis of spaceflown neonate swordtail fish Xiphophorus helleri as well as in 1 g control siblings. Spaceflight (16 days microgravity, (μg), STS-90 Neurolab Mission) yielded an increase in synaptic contacts within the vestibular nucleus descendens indicating that lack of input resulted in compensation processes. No effect of μg, however, was observed in the visual nucleus corticalis and in the vestibular nucleus magnocellularis which is situated in the close vicinity of the nucleus descendens. In contrast to the latter, the nucleus magnocellularis does not receive exclusively vestibular input, but inputs from the lateral line as well, possibly providing sufficient input at microgravity.

Preserving Plasticity: New Directions in Research for the Developing Brain

After completing this article, readers should be able to: 1. Characterize the process of corticogenesis. 2. Describe findings of magnetic resonance imaging of the developing brain. Cerebral development of the fetus is under genetic control, and during the third trimester of gestation, synapse development, dendritic spine elaboration, and cortical-cortical connections proceed as the period of developmental plasticity begins. In contrast to infants born at term, those who are born preterm can suffer significant developmental disability; many reports have shown that the neurodevelopmental outcome of very low-birthweight preterm infants is related directly to gestational age at birth. Infants weighing less than 1,000 g at birth now represent almost 1% of all live births in the United States, and the survival rate for this population approaches 85%. In stark contrast to the improved survival, however, are the emerging reports of neurodevelopmental disability in these very tiny and frequently critically ill infants. The incidence of cerebral palsy is increasing as the survival rate increases, and the incidence of cognitive deficits in this population has not changed during the past decade. The incidence of major neurodevelopmental handicaps in very preterm infants ranges from 12% to 32%, and even “healthy” preterm infants experience a high degree of educational difficulties. When we examined 200 very low-birthweight survivors of the Randomized Indomethacin Intraventricular Hemorrhage Prevention Trial who had reached 8 years of age, more than 50% required special assistance in school or were educated in full-time special education classrooms, and 25% already had repeated at least one grade in school. These data are consistent with those of other observers and indicate that preterm birth disrupts the normal genetically programmed series of events regulating corticogenesis in the developing brain. Intracranial hemorrhage (ICH), or hemorrhage into the germinal matrix tissues of the developing brain, is a major cause of neurodevelopmental handicap …

E4 allele dosage does not predict cholinergic activity or synapse loss in Alzheimer's disease.

To investigate the relationship between apolipoprotein E (APOE) genotype and both cholinergic dysfunction and synapse loss in AD. A reduction in neocortical synapses and marked losses in the cholinergic system occur in AD. It has been suggested that the number of APOE epsilon4 alleles is inversely related to choline acetyltransferase (ChAT) activity, thereby influencing cholinergic function. Whether APOE genotype may influence neocortical synapse loss remains unclear. An autopsy series of 182 patients with AD (National Institute on Aging and Consortium to Establish a Registry for Alzheimer's Disease criteria) and 16 normal controls (NC). APOE genotype was determined in blood samples or in postmortem brain tissue. Midfrontal synapse counts (AU/microg) were quantified by a dot-immunobinding assay for synaptophysin (Syn). Midfrontal ChAT activity (nmol/h/100 mg) was assessed using standard assays. Mean midfrontal ChAT activity and Syn were both significantly reduced in patients with AD compared with NC. The relationship between ChAT activity and number of epsilon4 allele copies in AD was complex, with ChAT activity lower in patients with either two or no epsilon4 alleles compared with those with one epsilon4 allele. There was no relationship between APOE genotype and synapse loss in AD. Syn density was almost identical across the three genotypes. Unlike other studies, we failed to detect a linear relationship between ChAT activity and number of epsilon4 allele copies in the midfrontal cortex of this large sample of patients with AD. Our data also show that the presence of epsilon4 allele does not influence midfrontal synapse loss in AD. This suggests that factors other than APOE genotype may be operative in the decline in midfrontal cholinergic function and synapses seen in AD.

Neurochemical Markers Do Not Correlate With Cognitive Decline in the Lewy Body Variant of Alzheimer Disease

Reductions in neocortical synapses and cholinergic function occur in patients with Alzheimer disease (AD) and in patients with the Lewy body variant of AD (LBV). The relation between these losses and cognitive decline has been reported frequently in patients with AD but remains unclear for patients with LBV. To investigate the relation between clinical markers of disease progression and choline acetyltransferase activity or synaptic density, measured by synaptophysin (Syn) level, in patients with LBV, and to investigate the relation of these neurochemical markers with one another. Brain specimens of 41 patients with autopsy-confirmed (National Institute on Aging criteria for AD) LBV were examined. The last Mini-Mental State Examination and Blessed Information-Memory-Concentration test scores before death were reviewed. Midfrontal synapse counts were quantified by a dot-immunobinding assay for Syn. Choline acetyltransferase activity of the midfrontal cortex was assayed by established protocols. The last Mini-Mental State Examination score before death did not correlate significantly with Syn level (n = 25, r = 0.25, P = .24); however, there was a trend toward significance for the relation between last Mini-Mental State Examination score and choline acetyltransferase activity (n = 39, r = 0.31, P = .05). The last Blessed Information-Memory-Concentration test score did not correlate with either Syn level (n = 24, r = -0.17, P = .44) or choline acetyltransferase activity (n = 39, r = -0.16, P = .33). Finally, there was only a modest correlation between Syn level and choline acetyltransferase activity (n = 25, r = 0.38, P = .06), which did not reach statistical significance. Unlike AD, neurochemical markers do not appear to correlate well with cognitive decline in LBV.

The effects of aging on layer 1 in area 46 of prefrontal cortex in the rhesus monkey.

The effect of age on layer 1 of area 46 of prefrontal cortex was determined in the cerebral cortices of 15 rhesus monkeys, 13 of which had been behaviorally tested. Five of the monkeys were young (5-7 years of age), three were middle-aged (9-12 years) and seven were old (24-32 years). It was found that with age, layer 1 becomes significantly thinner and the glial limiting membrane becomes thicker. Counts of synapses in layer 1 of seven of these monkeys using the physical disector method on thin sections revealed that compared to young monkeys, there is a 30-60% reduction in the density of synapses per unit volume in old monkeys. This loss of synapses is accompanied by a reduction in the frequency of profiles of postsynaptic dendrites and their spines from the neuropil of layer 1, indicating that some spiny dendrites that belong to the apical dendritic tufts of pyramidal cells are degenerating and being lost with age. Correlation of these morphological changes with the behavioral data shows that there is a significant correlation between the thickness of layer 1 and memory function, as measured by the 2 min delay condition of the delayed non-matching to sample task. Also, there is significant correlation between the numerical density of synapses in layer 1 and three of the behavioral measures used, as well as the Cognitive Impairment Index. Thus, the changes that occur with age in layer 1 provide one possible basis for the age-related cognitive impairment evidenced in monkeys and humans alike.

Correlation of nicotinic binding with neurochemical markers in Alzheimer's disease.

The loss of neocortical synapses that occurs in Alzheimer's disease (AD) has been shown to correlate with cognitive decline. In addition, marked losses in the cholinergic system in AD, specifically choline acetyltransferase (ChAT) activity and high affinity presynaptic neuronal nicotinic cholinergic receptors (nAChRs), have also been described. We hypothesized that in AD, the loss of [3H]-ligand binding to nAChRs, which are largely presynaptic, would correlate with changes in two other presynaptic markers: synaptophysin (Syn), a measure of synaptic density, and ChAT activity. The midfrontal (MF) cortex of 36 autopsy confirmed (NIA and CERAD criteria) AD patients (mean death age +/- SD 80.1 +/- 8.4 years) who met NINDS-ADRDA criteria for a clinical diagnosis of probable or possible AD, and 11 nondemented controls (mean death age +/- SD 77.9 +/- 8.0) were examined. Synapse counts were quantified by a dotimmunobinding assay for Syn. ChAT activity was assessed by standard biochemical assays. Nicotinic cholinergic receptor binding was assayed using the high affinity nicotinic agonist [3H]-(+/-)-epibatidine ([3H]-EPI). The mean +/- SD Syn in AD (83.4 +/- 31.9 arbitrary units (AU)/mg protein) was significantly lower than controls (126.1 +/- 19.9, p = 0.0003; t-test). The mean ChAT activity in AD (139.0 +/- 75.6 nmol ACh/hr/100 mg protein) was significantly lower than controls (219.6 +/- 70.8, p = 0.004). The mean [3H]-EPI total binding in AD (6.2 +/- 2.8 fmol/mg protein) was significantly lower than controls (14.8 +/- 3.2; p < 0.0001). Syn correlated with [3H]-EPI binding in AD (r = 0.48, p = 0.006; Pearson) but ChAT did not (r = -0.20, p = 0.34). We conclude that loss of high affinity nAChR binding correlates with loss of synapses in AD. The lack of correlation between [3H]-EPI binding and ChAT activity suggests that the targeted receptor populations may not be located exclusively on cholinergic neurons.

Lack of gonadotropin-positive feedback in the male rat is associated with lack of estrogen-induced synaptic plasticity in the arcuate nucleus.

We have demonstrated that estrogen induces synaptic reorganization in the hypothalamic arcuate nucleus of female rats during the ovarian cycle and proposed that estrogen-induced synaptic retraction plays a role in the disinhibition of gonadotropin secretion that occurs during the afternoon of proestrus. This so-called positive feedback of gonadotropins is developmentally determined. It is present in female rats and absent in males. To confirm the role of the estrogen-induced synaptic retraction in positive feedback, we tested whether administration of estrogen to male rats also fails to induce synaptic remodeling of the arcuate nucleus. Male and female rats were gonadectomized and studied as follows. One month following gonadectomy, animals received either a single injection of estradiol (100 micrograms/animal in sesame oil; 12 males and 12 females) or vehicle (6 males and 6 females). Twenty-four hours following injections, all animals in the vehicle-injected group and 6 animals of each sex in the treatment groups were sacrificed, while the rest of the animals were killed 48 h following the hormone injections (6 per group). As expected, quantitative electron microscopic analysis of the female arcuate nuclei revealed that compared to oil-injected controls, estradiol induced drastic decreases in the overall synapse counts by 24 h (121 +/- 10 vs. 74 +/- 5 synapses/1,000 microns membrane; p < 0.05). Synaptic counts had recovered to control levels by 48 h. On the contrary, in males, estradiol treatment did not cause changes in the total synapse counts at either time. As a further control, the lack of an estrogen-induced gonadotropin surge in long-term castrate males was also confirmed. Our study confirmed that in males estradiol does not alter the net synaptology of the arcuate nucleus or cause gonadotropin positive feedback. This is in clear contradistinction to females which show both synaptic plasticity and gonadotropin-positive feedback upon receiving exogenous or endogenous estrogen. The lack of estrogen-induced synaptic plasticity may be an underlying mechanism in the abolishment of positive gonadotropin, feedback in developing males and the development of constant estrus in aging female rats.

Ginseng root prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia.

The present study was designed to investigate the possible neuroprotective activity of ginseng roots in 5-min ischemic gerbils using a step-down passive avoidance task and subsequent neuron and synapse counts in the hippocampal CA1 region. The following drugs were administered for 7 days before the induced ischemia: red ginseng powder (RGP), crude ginseng saponin (CGS), crude ginseng non-saponin (CGNS), and pure ginsenosides Rb1, Rg1 and Ro. Oral administration of RGP significantly prevented the ischemia-induced decrease in response latency, as determined by the passive avoidance test, and rescued a significant number of ischemic hippocampal CA1 pyramidal neurons in a dose-dependent manner. Intraperitoneal injections of CGS exhibited a similar neuroprotective effect. CGNS had a significant but less potent protective effect against impaired passive avoidance task and degeneration of hippocampal CA1 neurons. Ginsenoside Rb1 significantly prolonged the response latency of ischemic gerbils and rescued a significant number of ischemic CA1 pyramidal neurons, whereas ginsenosides Rg1 and Ro were ineffective. Postischemic treatment with RGP, CGS or ginsenoside Rb1 was ineffective. The neuroprotective activities of RGP, CGS and ginsenoside Rb1 were confirmed by electron microscopy counts of synapses in individual strata of the CA1 field of ischemic gerbils pretreated with the drugs. These findings suggest that RGP and CGS are effective in the prevention of delayed neuronal death, and that ginsenoside Rb1 is one of the neuroprotective molecules within ginseng root.

A Spaceflight Study of Synaptic Plasticity in Adult Rat Vestibular Maculas

Behavioral signs of vestibular perturbation in altered gravity have not been well correlated with structural modifications in neurovestibular centers. This ultrastructural research investigated synaptic plasticity in hair cells of adult rat utricular maculas exposed to microgravity for nine days on a space shuttle. The hypothesis was that synaptic plasticity would be more evident in type II hair cells because they are part of a distributed modifying macular circuitry. All rats were shared with other investigators and were subjected to treatments unrelated to this experiment. Maculas were obtained from flight and control rats after shuttle return (R + 0) and nine days post-flight (R + 9). R + 9 rats had chromodacryorrhea, a sign of acute stress. Tissues were prepared for ultrastructural study by conventional methods. Ribbon synapses were counted in fifty serial sections from medial utricular macular regions of three rats of each flight and control group. Counts in fifty additional consecutive sections from one sample in each group established method reliability. All synapses were photographed and located to specific cells on mosaics of entire sections. Pooled data were analyzed statistically. Flown rats showed abnormal posture and movement at R + 0. They had statistically significant increases in total ribbon synapses and in sphere-like ribbons in both kinds of hair cells; in type II cells, pairs of synapses nearly doubled and clusters of 3 to 6 synapses increased twelve-fold. At R + 9, behavioral signs were normal. However, synapse counts remained high in both kinds of hair cells of flight maculas and were elevated in control type II cells. Only counts in type I cells showed statistically significant differences at R + 9. High synaptic counts at R + 9 may have resulted from stress due to experimental treatments. The results nevertheless demonstrate that adult maculas retain the potential for synaptic plasticity. Type II cells exhibited more synaptic plasticity, but space flight induced synaptic plasticity in type I cells.

Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity

Ultrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD) revealed that the number of synapses in lamina III of Brodmann's area 9 was significantly decreased when compared with the number in age-matched control brains (n = 9; postmortem time, less than 13 hours). Further decline in synaptic number was seen in age-matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini-Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini-Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined.(ABSTRACT TRUNCATED AT 250 WORDS)