No evidence of persisting unrepaired nuclear DNA single strand breaks in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT.

Background: It has been hypothesized in the literature that exposure to extremely low frequency electromagnetic fields (50 or 60 Hz) may lead to human health effects such as childhood leukemia or brain tumors. In a previous study investigating multiple types of cells from brain and kidney of the mouse (Acta Neuropathologica 2004; 107: 257-264), we found increased unrepaired nuclear DNA single strand breaks (nDNA SSB) only in epithelial cells of the choroid plexus in the brain using autoradiographic methods after a continuous eight-week 50 Hz magnetic field (MF) exposure of adult mice with flux density of 1.5 mT.

Presenilin 1-related alterations in DNA integrity in a transgenic mouse model of Alzheimer's disease.

The present study tested the hypothesis that mutations in amyloid precursor protein (APP) and presenilin (PS) 1 result in alterations in the amount of nuclear (n) DNA repair and nDNA damage in neurons in vivo. To this end, the relative amount of nDNA repair was measured in 8-month-old transgenic mice expressing either human mutant APP (APP751(SL) mice), human mutant PS1 (PS1(M146L) mice) or both human mutant APP and PS1 (APP751(SL)/PS1(M146L) mice) with unscheduled DNA synthesis, and the relative amount of nDNA single strand breaks (SSB) with in situ nick translation. APP751(SL)/PS1(M146L) mice showed a significantly decreased relative amount of nDNA repair in pyramidal cells in hippocampal area CA1/2 compared to APP751(SL) mice.

Microvessel length density, total length, and length per neuron in five subcortical regions in schizophrenia.

Recent studies (Prabakaran et al. in Mol Psychiat 9:684-697, 2004; Hanson and Gottesman in BMC Med Genet 6:7, 2005; Harris et al. in PLoS ONE 3:e3964, 2008) have suggested that microvascular abnormalities occur in the brains of patients with schizophrenia.

Selective loss of unmyelinated nerve fibers after extracorporeal shockwave application to the musculoskeletal system.

Application of extracorporeal shockwaves (ESW) to the musculoskeletal system may induce long-term analgesia in the treatment of chronic tendinopathies of the shoulder, heel and elbow. However, the molecular and cellular mechanisms behind this phenomenon are largely unknown. Here we tested the hypothesis that long-term analgesia caused by ESW is due to selective loss of nerve fibers in peripheral nerves.

Extracorporeal shockwave application to the distal femur of rabbits diminishes the number of neurons immunoreactive for substance P in dorsal root ganglia L5.

Application of extracorporeal shockwaves to the musculoskeletal system can induce long-term analgesia in the treatment of chronic painful diseases such as calcifying tendonitis of the shoulder, tennis elbow and chronic plantar fasciitis. However, the molecular and cellular mechanisms underlying this phenomenon are largely unknown. Recently it was shown that application of extracorporeal shockwaves to the distal femur of rabbits can lead to reduced concentration of substance P in the shockwaves' focal zone.

Neurons in the fusiform gyrus are fewer and smaller in autism.

Abnormalities in face perception are a core feature of social disabilities in autism. Recent functional magnetic resonance imaging studies showed that patients with autism could perform face perception tasks. However, the fusiform gyrus (FG) and other cortical regions supporting face processing in controls are hypoactive in patients with autism.

Caviomorph placentation as a model for trophoblast invasion.

The guinea pig and its relatives are promising candidates as animal models for studying trophoblast invasion. The origin, migration routes and kinetics of invasive trophoblast cells were examined in two caviomorph species. Histology and immunohistochemistry were done on placentas from 38 guinea pigs of days 20-47 and 13 degus of days 25-51 of gestation.

Tau-4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice.

Differential isoform expression and phosphorylation of protein tau are believed to regulate the assembly and stabilization of microtubuli in fetal and adult neurons. To define the functions of tau in the developing and adult brain, we generated transgenic mice expressing the human tau-4R/2N (htau-4R) isoform on a murine tau null background, by a knockout/knockin approach (tau-KOKI). The main findings in these mice were the significant increases in hippocampal volume and neuronal number, which were sustained throughout adult life and paralleled by improved cognitive functioning.

Moderate loss of cerebellar Purkinje cells after chronic bilateral common carotid artery occlusion in rats.

Pathological effects of moderate ischemia (oligemia, hypoperfusion) are relevant in relation to vascular factors in dementia. Chronic bilateral common carotid artery occlusion (BCCAO) in adult Wistar rats induces oligemia and leads to acute changes in gene expression, subacute changes in cortical astrocytes and prolonged changes in white matter tracts, while largely sparing neurons in the forebrain areas. Dilation and remodeling of the basilar artery ensures blood flow to the forebrain.

Volume, neuron density and total neuron number in five subcortical regions in schizophrenia.

Several studies have pointed to alterations in mean volumes, neuron densities and total neuron numbers in the caudate nucleus (CN), putamen, nucleus accumbens (NA), mediodorsal nucleus of the thalamus (MDNT) and lateral nucleus of the amygdala (LNA) in schizophrenia. However, the results of these studies are conflicting and no clear pattern of alterations has yet been established in these subcortical regions, possibly due to differences in quantitative histological methods used as well as differences in the investigated case series. The present study investigates these subcortical regions in both hemispheres of the same post-mortem brains for volume, neuron density and total neuron number with high-precision design-based stereology.

Behavioral abnormalities precede neuropathological markers in rats transgenic for Huntington's disease.

Huntington's disease (HD) is caused by an expanded CAG repeat leading to the synthesis of an aberrant protein and to the formation of polyglutamine (polyQ)-containing inclusions and aggregates. Limited information is available concerning the association of neuropathological markers with the development of behavioral markers in HD. Using a previously generated transgenic rat model of HD (tgHD rat), we performed association studies on the time-course of behavioral symptoms (motor function, learning, anxiety) and the appearance of striatal atrophy, 1C2 immunopositive aggregates and polyQ recruitment sites, a precursor to these aggregates.

Selective striatal neuron loss and alterations in behavior correlate with impaired striatal function in Huntington's disease transgenic rats.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by selective striatal neuron loss and motor, cognitive and affective disturbances. The present study aimed to test the hypothesis of adult-onset neuron loss in striatum and frontal cortical layer V as well as alterations in behavior pointing to impaired striatal function in a recently developed transgenic rat model of HD (tgHD rats) exhibiting enlarged ventricles, striatal atrophy and pycnotic pyramidal cells in frontal cortical layer V. High-precision design-based stereological analysis revealed a reduced mean total number of neurons in the striatum but not in frontal cortical layer V of 12-month-old tgHD rats compared with age-matched wild-type controls.

The aging brain: accumulation of DNA damage or neuron loss?

Age-related molecular and cellular alterations in the central nervous system are known to show selectivity for certain cell types and brain regions. Among them age-related accumulation of nuclear (n) DNA damage can lead to irreversible loss of genetic information content. In the present study on the aging mouse brain, we observed a substantial increase in the amount of nDNA single-strand breaks in hippocampal pyramidal and granule cells as well as in cerebellar granule cells but not in cerebellar Purkinje cells.

Mean cell spacing abnormalities in the neocortex of patients with schizophrenia.

It has been postulated that the prefrontal cortices of schizophrenic patients have significant alterations in their interneuronal (neuropil) space. The present study re-examines this finding based on measurements of mean cell spacing within the cell minicolumn. The population studied consisted of 13 male schizophrenic patients (DSM-IV criteria) and 13 age-matched controls.

Prenatal protracted irradiation at very low dose rate induces severe neuronal loss in rat hippocampus and cerebellum.

Prenatal irradiation is known to damage the developing brain. However, little is known about the consequences of very low dose rate prenatal protracted irradiation over several days on neuron numbers in the offspring brain, and on volumes of the corresponding brain regions. Pregnant Wistar rats were exposed either to a protracted gamma irradiation from embryonic day (E) 13 to E16 (0.

Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease.

According to the "amyloid hypothesis of Alzheimer's disease," beta-amyloid is the primary driving force in Alzheimer's disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant beta-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L).

50-Hz magnetic field exposure influences DNA repair and mitochondrial DNA synthesis of distinct cell types in brain and kidney of adult mice.

Despite several recent investigations, the impact of whole-body magnetic field exposure on cell-type-specific alterations due to DNA damage and DNA repair remains unclear. In this pilot study adult mice were exposed to 50-Hz magnetic field (mean value 1.5 mT) for 8 weeks or left unexposed.

No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment.

Previous studies in the literature have resulted in conflicting reports on the potential neurotoxicity of the beta-cleaved Alzheimer's disease C-terminal fragment (beta-CTF) of beta-amyloid precursor protein in vivo. To readdress this question by rigorous quantitative methods, we analyzed transgenic mice expressing human beta-CTF with the I45F mutation (SPA4CT) under control of the prion protein promoter by stereological techniques. The transgene was expressed in hippocampus and cortex in large pyramidal neurons and in dentate gyrus granule cells.

The aging brain: less neurons could be better.

Molecular and cellular markers of age-related alterations in the brain vary significantly between different brain regions and between different types of neurons. In contrast to what had been thought for years, it has recently become clear that only specific types of neurons show an age-related loss of cells. Based on previous work we hypothesize that there is an interrelationship between two important processes in the aging brain: some types of neurons in the aging brain show an accumulation of unrepaired nuclear (n) nDNA damage since no cells are lost during aging.

Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation.

In the third trimester of normal pregnancy, the mother tolerates daily shedding of several grams of dying placental trophoblast into the maternal circulation. The balance between apoptotic and necrotic shedding is presently unknown. Since pre-eclampsia is characterized by an altered placental oxygenation and increased trophoblast shedding, we investigated the role of oxygen on the balance of apoptotic versus necrotic trophoblast shedding in vitro.

Antioxidants and Alzheimer's disease: from bench to bedside (and back again).

Purpose Of Review: Accumulating evidence from both animal and human studies indicates a major role for oxidative damage in the pathogenesis of Alzheimer's disease, occurring even before symptoms arise and both beta-amyloid-containing plaques and neurofibrillary tangles are formed. This raises the possibility of preventing, or at least slowing down, the progression of Alzheimer's disease by the use of antioxidants. In this review, we present recent studies on the association between oxidative stress and Alzheimer's disease pathology, and on the efficacy of dietary, exogenous antioxidants to prevent or attenuate the progression of Alzheimer's disease.

Cell-Type-Specific Differences in Age-Related Changes of DNA Repair in the Mouse Brain - Molecular Basis for a New Approach to Understand the Selective Neuronal Vulnerability in Alzheimer's Disease.

Despite intensive research over the last decades, the molecular basis of the selective neuronal vulnerability in Alzheimer's disease (AD) is still largely unknown. In this context we have recently shown by means of quantitative autoradiography that presumably all types of neurons in the mouse brain suffer an age-related decrease in the rate of mitochondrial DNA synthesis, while in contrast only some distinct types of neurons showed a decrease in the rate of spontaneous overall nuclear DNA repair measured as unscheduled nuclear DNA synthesis. Most strikingly, there was a highly positive correlation to be found between that group of neurons in the mouse brain showing the age-related decrease in the rate of spontaneous overall nuclear DNA repair (pattern X) and the pattern of neurons in the human brain which - according to the literature - are affected by the formation of neurofibrillary tangles in AD (pattern Y).

Depression: reduced number of granule cells in the hippocampus of female, but not male, rats due to prenatal restraint stress.

It has been hypothesized that decreased neurogenesis in the dentate gyrus may be involved in mediating depressive disorders, which are 1.5-3 times more frequent in women than in men. Additionally, prenatal stress may increase the risk of developing depression in adulthood.

Altered spatial arrangement of layer V pyramidal cells in the mouse brain following prenatal low-dose X-irradiation. A stereological study using a novel three-dimensional analysis method to estimate the nearest neighbor distance distributions of cells in thick sections.

Prenatal X-irradiation, even at doses <1 Gy, can induce spatial disarray of neurons in the brains of offspring, possibly due to disturbed neuronal migration. Here we analyze the effects of prenatal low-dose X-irradiation using a novel stereological method designed to investigate the three-dimensional (3D) spatial arrangement of neurons in thick sections. Pregnant mice were X-irradiated with 50 cGy on embryonic day 13 or were sham-irradiated.