In this investigation, we hypothesize that quality of oral anticoagulation (OA) and long-term outcome after mechanical heart valve (MHV) replacement with self-management (Self-M) of OA is superior to conventional anticoagulation treatment (Conv-T), even in outside trial conditions. One hundred sixty patients (78.8% aortic valve replacements) were trained in international normalized ratio Self-M and 260 patients (86.2% aortic valve replacements) preferred Conv-T. Mean follow-up was 8.6 ± 2.1 years, representing 3612 patient-years. During follow-up, 37.2% bleedings and 10.6% thromboembolic events were recorded in the Self-M group versus 39.6% bleedings (P = 0.213) and 15.4% thromboembolic events (P = 0.064) in the Conv-T group. Serious adverse events were significantly lower in the Self-M group [grade III bleeding events causing disability or death: 0 versus 4.6% (P = 0.03); grade III thromboembolic events: 0.6 versus 5.0% (P = 0.011)]. Patients with Self-M were significantly more satisfied with their OA management and their quality of life (P < 0.001). Actuarial survival after 1, 5 and 10 years was 100, 99 and 97 with Self-M and 100, 95 and 81% with Conv-T, respectively (P < 0.001). Univariate risk factors for mortality were age (P = 0.008), type of operation (P = 0.021) and conventional OA (P < 0.001). In multivariate analysis, only conventional OA reached significance (P < 0.001). We conclude that in a routine setting under outside trial conditions Self-M of OA improves long-term outcome and treatment quality.
Self-management; Home monitoring; Heart valve replacement; International normalized ratio; Anticoagulation; Oral
Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a spatial resolution in the centimeter range. This resolution is poor compared to other functional imaging tools.
However, recently it was shown that diffuse optical tomography (DOT) as an extension of NIRS based on high-density (HD) probe arrays and supplemented by an advanced image reconstruction procedure allows describing activation patterns with a spatial resolution in the millimeter range. Building on these findings, we hypothesize that HD-DOT may render very focal activations accessible which would be missed by the traditionally used sparse arrays. We examined activation patterns in the primary somato-sensory cortex, since its somatotopic organization is very fine-grained. We performed a vibrotactile stimulation study of the first and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT imaging system for achieving a higher resolution than conventional topographic NIRS. To compare the results to a well established high-resolution imaging technique, the same paradigm was investigated in the same subjects by means of functional magnetic resonance imaging (fMRI). In this work, we tested the advantage of ultrahigh-density probe arrays and show that highly focal activations would be missed by classical next-nearest neighbor NIRS-approach, but also by DOT, when using a sparse probe array. Distinct activation patterns for both fingers correlated well with the expected neuro-anatomy in five of eight subjects. Additionally we show that activation for different fingers are projected to different tissue depths in the DOT image. Comparison to the fMRI data yielded similar activation foci in seven out of ten finger representations in these five subjects when comparing the lateral localization of DOT and fMRI results.
near infrared spectroscopy; NIRS; diffuse optical tomography; DOT; high-density diffuse optical tomography human; brain; somatotopy; vibrotactile stimulation; comparison NIRS fMRI; multimodal imaging
Aberrations in epigenetic marks have been associated with aging of the brain while caloric restriction (CR) and upregulation of endogenous antioxidants have been suggested as tools to attenuate the aging process. We have recently observed age-related increases in levels of 5-methylcytidine (5-mC) and DNA methyltransferase 3a (Dnmt3a) in the mouse hippocampus. Most of those age-related changes in these epigenetic relevant markers were prevented by CR but not by transgenic overexpression of the endogenous antioxidant superoxide dismutase 1 (SOD1). As recent work has suggested a distinct role for hydroxymethylation in epigenetic regulation of gene expression in the brain, the current study investigated age-related changes of 5-hydroxymethylcytosine (5-hmC) in the mouse hippocampus, and furthermore tested whether CR and transgenic upregulation of SOD1 affected any age-related changes in 5-hmC. Immunohistochemical analyses of 5-hmC in 12- and 24-month-old wild-type and transgenic mice overexpressing SOD1, which were kept under either a control or a calorie restricted diet, revealed an increase of 5-hmC immunoreactivity occurring with aging in the hippocampal dentate gyrus, CA3 and CA1–2 regions. Moreover, CR, but not overexpression of SOD1, prevented the age-related increase in the CA3 region. These region-specific findings indicate that the aging process in mice is connected with epigenetic changes and suggest that the beneficial actions of CR may be mediated via epigenetic mechanisms such as methylation and hydroxymethylation of DNA.
Aging; Epigenesis; Epigenetics; DNA hydroxymethylation; 5-hydroxymethylcytosine; Caloric restriction; Antioxidants; superoxide dismutase (SOD); Hippocampus
Tissue engineering represents a promising new method for treating heart valve diseases. The aim of this study was evaluate the importance of conditioning procedures of tissue engineered polyurethane heart valve prostheses by the comparison of static and dynamic cultivation methods.
Human vascular endothelial cells (ECs) and fibroblasts (FBs) were obtained from saphenous vein segments. Polyurethane scaffolds (n = 10) were primarily seeded with FBs and subsequently with ECs, followed by different cultivation methods of cell layers (A: static, B: dynamic). Group A was statically cultivated for 6 days. Group B was exposed to low flow conditions (t1= 3 days at 750 ml/min, t2= 2 days at 1100 ml/min) in a newly developed conditioning bioreactor. Samples were taken after static and dynamic cultivation and were analyzed by scanning electron microscopy (SEM), immunohistochemistry (IHC), and real time polymerase chain reaction (RT-PCR).
SEM results showed a high density of adherent cells on the surface valves from both groups. However, better cell distribution and cell behavior was detected in Group B. IHC staining against CD31 and TE-7 revealed a positive reaction in both groups. Higher expression of extracellular matrix (ICAM, Collagen IV) was observed in Group B. RT- PCR demonstrated a higher expression of inflammatory Cytokines in Group B.
While conventional cultivation method can be used for the development of tissue engineered heart valves. Better results can be obtained by performing a conditioning step that may improve the tolerance of cells to shear stress. The novel pulsatile bioreactor offers an adequate tool for in vitro improvement of mechanical properties of tissue engineered cardiovascular prostheses.
Tissue engineering; Heart valve; Polyurethane scaffold; Static cultivation; Dynamic cultivation
Non-invasive diffuse optical tomography (DOT) of the adult brain has recently been shown to improve the spatial resolution for functional brain imaging applications. Here we show that high-resolution (HR) DOT is also advantageous for clinical perfusion imaging using an optical contrast agent. We present the first HR-DOT results with a continuous wave near infrared spectroscopy setup using a dense grid of optical fibers and indocyanine green (ICG) as an exogenic contrast agent. We find an early arrival of the ICG bolus in the intracerebral tissue and a delayed arrival of the bolus in the extracerebral tissue, achieving the separation of both layers. This demonstrates the method’s potential for brain perfusion monitoring in neurointensive care patients.
(170.2655) Functional monitoring and imaging; (170.6280) Spectroscopy, fluorescence and luminescence; (170.6960) Tomography
Aberrant DNA methylation patterns have been linked to molecular and cellular alterations in the aging brain. Caloric restriction (CR) and upregulation of antioxidants have been proposed as interventions to prevent or delay age-related brain pathology. Previously, we have shown in large cohorts of aging mice, that age-related increases in DNA methyltransferase 3a (Dnmt3a) immunoreactivity in the mouse hippocampus were attenuated by CR, but not by overexpression of superoxide dismutase 1 (SOD1). Here, we investigated age-related alterations of 5-methylcytidine (5-mC), a marker of DNA methylation levels, in a hippocampal subregion-specific manner. Examination of 5-mC immunoreactivity in 12- and 24-month-old wild type (WT) mice on control diet, mice overexpressing SOD1 on control diet, wild type mice on CR, and SOD1 mice on CR, indicated an age-related increase in 5-mC immunoreactivity in the hippocampal dentate gyrus, CA3, and CA1–2 regions, which was prevented by CR but not by SOD1 overexpression. Moreover, positive correlations between 5-mC and Dnmt3a immunoreactivity were observed in the CA3 and CA1–2. These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging.
Aging; Epigenesis; Epigenetics; DNA methylation; 5-methylcytidine (5-mC); Caloric restriction; Antioxidants; Superoxide dismutase (SOD); Hippocampus
Valvular aortic stenosis is a common disease in the elderly, often in multimorbid patients. It is often associated with coronary artery disease and peripheral artery disease. In this situation, the risk of conventional open-heart surgery is too high, and other treatment strategies have to be evaluated.
A 79-year-old female patient with severe aortic stenosis, coronary artery disease and end-stage chronic obstructive pulmonary disease suffering from dyspnea at rest and permanently dependent on oxygen was treated in three steps. Firstly, her pulmonary infection was treated with antibiotics for 7 days. Then, the left anterior descending artery was stented (bare-metal stent). In the same session, valvuloplasty of the aortic valve was performed. She was sent to rehabilitation to improve her pulmonary condition and took clopidogrel for 4 weeks. Finally, she underwent transapical aortic valve replacement. She was released to rehabilitation on postoperative day 12.
A combination of modern interventional and minimally invasive surgical techniques to treat aortic stenosis and coronary heart disease can be a viable option for multimorbid patients with extremely high risk in conventional open-heart surgery.
aortic stenosis; transapical aortic valve replacement; minimally invasive cardiac surgery
Left atrial intramural hematoma is a seldom cause of left atrial mass. It has been described to occur spontaneously, after interventional procedures, after blunt chest trauma, or after aortocoronary bypass surgery. We present a case of mitral valve replacement together with the removal of a large intraatrial space-occupying lesion. Intraoperative transesophageal echocardiography confirmed a successful resection of this mass. Surprisingly, upon admission to ICU, transesophageal and transthoracic echocardiography revealed a recurrence of an intramural lesion, closest matching a hematoma, which was confirmed by contrast-enhanced computed tomography. Surgical intervention was thoroughly discussed but a conservative management was favoured. 3 months after surgery, a reassessed transthoracic echocardiography and computed tomography demonstrated an almost complete resolution of the pre-existing hematoma.
Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by amyloid plaque accumulation, intracellular tangles and neuronal loss in selective brain regions. The frontal cortex, important for executive functioning, is one of the regions that are affected. Here, we investigated the neurodegenerative effects of mutant human amyloid precursor protein (APP) and presenilin 1 (PS1) on frontal cortex neurons in APP/PS1KI mice, a transgenic mouse model of AD, expressing two mutations in the human APP, as well as two human PS1 mutations knocked-in into the mouse PS1 gene in a homozygous (ho) manner. Although the hippocampus is significantly affected in these mice, very little is known about the effects of these mutations on selective neuronal populations and plaque load in the frontal cortex. In this study, cytoarchitectural changes were characterized using high precision design-based stereology to evaluate plaque load, total neuron numbers, as well as total numbers of parvalbumin- (PV) and calretinin- (CR) immunoreactive (ir) neurons in the frontal cortex of 2- and 10-month-old APP/PS1KI mice. The frontal cortex was divided into two subfields: layers II–IV and layers V–VI, the latter of which showed substantially more extracellular amyloid-beta aggregates. We found a 34% neuron loss in layers V–VI in the frontal cortex of 10-month-old APP/PS1KI mice compared to 2-month-old, while there was no change in PV- and CR-ir neurons in these mice. In addition, the plaque load in layers V–VI of 10-month-old APP/PS1KI mice was only 11% and did not fully account for the extent of neuronal loss. Interestingly, an increase was found in the total number of PV-ir neurons in all frontal cortical layers of single transgenic APP mice and in layers II–IV of single transgenic PS1ho mice between 2 and 10 months of age. In conclusion, the APP/PS1KI mice provide novel insights into the regional selective vulnerability in the frontal cortex during AD that, together with previous findings in the hippocampus, are remarkably similar to the human situation.
Alzheimer’s disease; Neuropathology; Stereology; Frontal cortex; Mouse model
Hippocampal atrophy and neuron loss are commonly found in Alzheimer’s disease (AD). However, the underlying molecular mechanisms and the fate in the AD hippocampus of subpopulations of interneurons that express the calcium-binding proteins parvalbumin (PV) and calretinin (CR) has not yet been properly assessed. Using quantitative stereologic methods, we analyzed the regional pattern of age-related loss of PV- and CR-immunoreactive (ir) neurons in the hippocampus of mice that carry M233T/L235P knocked-in mutations in presenilin-1 (PS1) and overexpress a mutated human beta-amyloid precursor protein (APP), namely, the APPSL/PS1 KI mice, as well as in APPSL mice and PS1 KI mice. We found a loss of PV-ir neurons (40–50%) in the CA1-2, and a loss of CR-ir neurons (37–52%) in the dentate gyrus and hilus of APPSL/PS1 KI mice. Interestingly, comparable PV- and CR-ir neuron losses were observed in the dentate gyrus of postmortem brain specimens obtained from patients with AD. The loss of these interneurons in AD may have substantial functional repercussions on local inhibitory processes in the hippocampus.
Alzheimer’s disease; Amyloid precursor protein; Calcium-binding proteins; Hippocampus; Presenilin-1; Stereology
Wolfram syndrome 1 (WFS1, OMIM 222300), a rare genetic disorder characterized by optic nerve atrophy, deafness, diabetes insipidus and diabetes mellitus, is caused by mutations of WFS1, encoding WFS1/wolframin. Non-syndromic WFS1 variants are associated with the risk of diabetes mellitus due to altered function of wolframin in pancreatic islet cells, expanding the importance of wolframin. This study extends a previous report for the monkey retina, using immunohistochemistry to localize wolframin on cryostat and paraffin sections of human retina. In addition, the human retinal pigment epithelial (RPE) cell line termed ARPE-19 and retinas from both pigmented and albino mice were studied to assess wolframin localization. In the human retina, wolframin was expressed in retinal ganglion cells, optic axons and the proximal optic nerve. Wolframin expression in the human retinal pigment epithelium (RPE) was confirmed with intense cytoplasmic labeling in ARPE-19 cells. Strong labeling of the RPE was also found in the albino mouse retina. Cryostat sections of the mouse retina showed a more extended pattern of wolframin labeling, including the inner nuclear layer (INL) and photoreceptor inner segments, confirming the recent report of Kawano et al. (J. Comp. Neurol. 2008: 510, 1-23). Absence of these cells in the human specimens despite the use of human-specific antibodies to wolframin may be related to delayed fixation. Loss of wolframin function in RGCs and the unmyelinated portion of retinal axons could explain optic nerve atrophy in Wolfram Syndrome 1.
According to a long-standing hypothesis, aging is mainly caused by accumulation of nuclear (n) DNA damage in differentiated cells such as neurons due to insufficient nDNA repair during lifetime. In line with this hypothesis it was until recently widely accepted that neuron loss is a general consequence of normal aging, explaining some degree of decline in brain function during aging. However, with the advent of more accurate procedures for counting neurons, it is currently widely accepted that there is widespread preservation of neuron numbers in the aging brain, and the changes that do occur are relatively specific to certain brain regions and types of neurons. Whether accumulation of nDNA damage and decline in nDNA repair is a general phenomenon in the aging brain or also shows cell-type specificity is, however, not known. It has not been possible to address this issue with the biochemical and molecular-biological methods available to study nDNA damage and nDNA repair. Rather, it was the introduction of autoradiographic methods to study quantitatively the relative amounts of nDNA damage (measured as nDNA single-strand breaks) and nDNA repair (measured as unscheduled DNA synthesis) on tissue sections that made it possible to address this question in a cell-type-specific manner under physiological conditions. The results of these studies revealed a formerly unknown inverse relationship between age-related accumulation of nDNA damage and age-related impairment in nDNA repair on the one hand, and the age-related, selective, loss of neurons on the other hand. This inverse relation may not only reflect a fundamental process of aging in the central nervous system but also provide the molecular basis for a new approach to understand the selective neuronal vulnerability in neurodegenerative diseases, particularly Alzheimer’s disease.
Aging; Alzheimer’s disease; Brain; DNA damage; DNA repair
It has been proposed that schizophrenia results partly from altered brain connectivity. Gene microarray analyses performed in gray matter have indicated that several myelin-related genes normally expressed in oligodendrocytes have decreased expression levels in schizophrenia. These data suggest that oligodendrocytes may be involved in the deficits of schizophrenia and may be decreased in number in the disease. The anterior cingulate cortex in particular has been demonstrated to be affected in schizophrenia, with studies reporting altered neuronal arrangement, decreased anisotropy in diffusion tensor images, and hypometabolism. We used a stereologic nearest-neighbor estimator of spatial distribution to investigate oligodendrocytes in the anterior cingulum bundle using postmortem tissue from 13 chronic schizophrenics and 13 age-matched controls. Using a spatial point pattern analysis, we measured the degree of oligodendrocyte clustering by comparing the probability of finding a nearest-neighbor at a given distance in schizophrenics and controls. At the same time, we also estimated the number and density of oligodendrocytes in the region of interest. In the present study, we found no significant differences in the oligodendrocyte distribution or density in the cingulum bundle between the two groups, in contrast to earlier data from the prefrontal subcortical white matter. These results suggest that a more subtle oligodendrocyte or myelin anomaly may underlie the structural deficits observed by brain imaging in the cingulum bundle in schizophrenia.
schizophrenia; oligodendrocyte; cingulate gyrus; stereology
Non-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanning environment. Beyond physiological and psychological research, bedside monitoring and neurorehabilitation may be relevant clinical applications that are yet little explored. A major obstacle to advocate the tool in clinical research is insufficient spatial resolution. Based on a multi-distance high-density optical imaging setup, we here demonstrate a dramatic increase in sensitivity of the method. We show that optical imaging allows for the differentiation between activations of single finger representations in the primary somatosensory cortex (SI). Methodologically our findings confirm results in a pioneering study by Zeff et al. (2007) and extend them to the homuncular organization of SI. After performing a motor task, eight subjects underwent vibrotactile stimulation of the little finger and the thumb. We used a high-density diffuse-optical sensing array in conjunction with optical tomographic reconstruction. Optical imaging disclosed three discrete activation foci one for motor and two discrete foci for vibrotactile stimulation of the first and fifth finger, respectively. The results were co-registered to the individual anatomical brain anatomy (MRI) which confirmed the localization in the expected cortical gyri in four subjects. This advance in spatial resolution opens new perspectives to apply optical imaging in the research on plasticity notably in patients undergoing neurorehabilitation.
near-infrared spectroscopy; optical imaging; optical tomography; somatotopy; somatosensory system; vibrotactile stimulation
Hypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system (CNS).
Mice with a null mutation in the low-density lipoprotein receptor (LDLR) gene as well as C57BL/6J mice fed a high cholesterol diet developed a distinct microvascular pathology in the CNS that differs from cholesterol-induced atherosclerotic disease. Microvessel diameter was increased but microvascular density and length were not consistently affected. Degenerative changes and thickened vascular basement membranes were present ultrastructurally. The observed pathology shares features with the microvascular pathology of Alzheimer's disease (AD), including the presence of string-like vessels. Brain apolipoprotein E levels which have been previously found to be elevated in LDLR-/- mice were also increased in C57BL/6J mice fed a high cholesterol diet.
In addition to its effects as an inducer of atherosclerosis in medium to large sized arteries, hypercholesterolemia also induces a microvascular pathology in the CNS that shares features of the vascular pathology found in AD. These observations suggest that high cholesterol may induce microvascular disease in a range of CNS disorders including AD.
True aneurysms of the ascending aorta often remain undetected, yet their sequelae carry a high rate of mortality and morbidity. The operative risk of nonemergent replacement of the ascending aorta is low. It is important to consider quality of life in determining the most appropriate treatment for patients who have aneurysms but have not yet experienced major complications.
From January 1999 to December 2003, 134 consecutive patients underwent replacement of a dilated ascending aorta at our center. Another 124 patients with acute or chronic aortic dissections, aortic rupture, or intramural hematoma were excluded. Standard SF-36 and general health questionnaires were sent to all 124 survivors who could be traced. Follow-up was 98.4% complete. The mean age of the survivors was 61.7 ± 11 years, and 63.4% were men. Operative procedures consisted of supracoronary replacement of the ascending aorta in 35.9%, the Wheat procedure in 44%, the David procedure in 11.2%, the Bentall–DeBono procedure in 9%, and the Cabrol procedure in 2.2%. Patients were monitored until May 2005.
Thirty-day and midterm mortality rates were 3.7% and 3.9%, respectively. Morbidity due to stroke was 6%, to bleeding 6%, and to myocardial infarction 4.4%. Postoperative quality-of-life evaluation revealed many subscales of SF-36 that were below the norm when compared with a standard population in physically dominated categories.
Replacement of the dilated ascending aorta carries acceptable risk in regard to operative death and postoperative quality of life, although this last showed some decline in comparison with quality of life in a normal, healthy population.
Aortic aneurysm, thoracic/surgery; blood vessel prosthesis; cardiac surgical procedures/adverse effects; health status indicators; health surveys; follow-up studies; quality of life; reference values; treatment outcome
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital defect. This anomaly leads to a coronary hypoperfusion phenomenon and to substantial left ventricular dysfunction caused by abnormal perfusion of the left ventricle. The optimal surgical management of such cases is not clearly established.
Here, we report the successful anatomic repair of ALCAPA arising from the non-facing sinus of Valsalva of the pulmonary artery in a 5-kg patient. In order to perform the repair, we created an autologous extrapulmonary tunnel (from a pulmonary artery flap and autologous pericardium), which we implanted into the ascending aorta. Because of post-cardiotomy heart failure, we implanted an extracorporeal membrane oxygenation device during the same procedure. After recovery of the failing heart, the device was easily ex-planted, and the patient was discharged from the hospital on postoperative day 30.
Coronary vessel anomalies/radiography/surgery; infant; extracorporeal membrane oxygenation; heart disease, congenital; heart failure, congestive; pulmonary artery/abnormalities; vascular surgical procedures/methods
High oxygen consumption and cyclical changes related to dark-adaptation are characteristic of the outer retina. Oxygenation changes may contribute to the selective vulnerability of the retina in retinitis pigmentosa (RP) patients, especially for those forms involving genes with global cellular functions. Genes coding for components of the U4/U6.U5 tri small nuclear ribonucleoprotein (tri-snRNP) complex of the spliceosome stand out, because mutations in four genes cause RP, i.e., RP9 (PAP1), RP11 (PRPF31), RP13 (PRPF8), and RP18 (PRPF3), while there is no degeneration outside the retina despite global expression of these genes. With the assumption that variable oxygenation plays a role in RP forms related to pre-mRNA splicing and the retina and brain are similar, we searched a data collection of ischemia-hypoxia regulated genes of the brain for oxygen regulated genes of the U4/U6.U5 tri-snRNP complex.
A database of ischemia-hypoxia response (IHR) genes in the brain was generated from gene expression profiling studies [n=24]. Public databases (NCBI) were searched for RP genes with global function that are expressed in the brain. From the IHR gene list, we extracted genes that were directly related to retinal degeneration through a listed mutation (OMIM, Retnet, RISN). The database was then examined for indirect links to RP forms affecting the U4/U6.U5 tri-snRNP complex by searching for IHR genes contributing to this complex. Potential expression of matched genes in the retina was ascertained using NEIBank. Immunohistochemistry was used to localize a selected protein of the U4/U6.U5 tri-snRNP complex in cynomolgus monkey and human retina specimens.
The approach identified genes that cause retinal degeneration (CNGB1, SEMA4A, RRG4) or developmental changes (SOX2) when mutated. One IHR gene, Pim1, is the immediate binding partner for PAP1 (RP9). Three IHR genes linked the U4/U6.U5 tri-snRNP complex to regulation by oxygenation: PRPF4; SART1, also known as 110 kDa SR-related protein of the U4/U6.U5 tri-snRNP or as hypoxia associated factor (HAF); and LSM8, U6 snRNA-associated Sm-like protein. The 110 kDa SR-related protein was localized in all retinal cells including photoreceptors.
Regulation by changes in oxygenation within the U4/U6.U5 tri-snRP complex could be particularly important for photoreceptors where oxygen consumption follows a circadian rhythm. If the U4/U6.U5 tri-snRP complex is already impaired by mutations in any of the four genes causing RP, it may be unable to follow properly the physiological demands of oxygenation which are mediated by the four hypoxia-regulated proteins emerging in this study. Selective vulnerability may involve complex combinations of widely expressed genes, specific cellular functions and local energy availability.
Both prenatal stress (PS) and postnatal chronic mild stress (CMS) are associated with behavioral and mood disturbances in humans and rodents. The aim of this study was to reveal putative PS- and/or CMS-related changes in basal spine morphology and density of pyramidal neurons in the rat medial prefrontal cortex (mPFC).
We show that rats exposed to PS and/or CMS display changes in the morphology and number of basal spines on pyramidal neurons in the mPFC. CMS had a negative effect on spine densities, particularly on spines of the mushroom type, which are considered to form stronger and more stable synapses than other spine types. PS alone did not affect spine densities, but had a negative effect on the ratio of mushroom spines. In addition, PS seemed to make rats less responsive to some of the negative effects of CMS, which supports the notion that PS represents a predictive adaptive response.
The observed changes may represent a morphological basis of PS- and CMS-related disturbances, and future studies in the field should not only consider total spine densities, but also separate between different spine types.
Neuroinflammation, initiated by cerebral infection, is increasingly postulated as an aetiological factor in neurodegenerative diseases such as Alzheimer’s disease (AD). We investigated whether Chlamydia pneumoniae (Cpn) infection results in extracellular aggregation of amyloid beta (Aβ) in BALB/c mice. At 1 week post intranasal infection (p.i.), Cpn DNA was detected predominantly in the olfactory bulbs by PCR, whereas brains at 1 and 3 months p.i. were Cpn negative. At 1 and 3 months p.i., extracellular Aβ immunoreactivity was detected in the brain of Cpn-infected mice but also in the brain of mock-infected mice and mice that were neither Cpn infected nor mock infected. However, these extracellular Aβ aggregates showed morphological differences compared to extracellular Aβ aggregates detected in the brain of transgenic APP751SL/PS1M146L mice. These data do not unequivocally support the hypothesis that Cpn infection induces the formation of AD-like Aβ plaques in the brain of BALB/c mice, as suggested before. However, future studies are required to resolve these differences and to investigate whether Cpn is indeed an etiological factor in AD pathogenesis.
Neuroinflammation; Chlamydia pneumoniae; Amyloid-beta