Neurogenic Processes Are Induced by Very Short Periods of Voluntary Wheel-Running in Male Mice

Even in the adult mammalian brain progenitor cells proliferate and give rise to young neurons which integrate into the neuronal network. The dentate gyrus possesses such a neurogenic niche reactive to external stimuli like physical activity. In most studies mice or rats have been exposed to wheel running for periods of several weeks to activate neurogenesis while early neurogenic processes induced by very short running periods are less well understood. To address this issue, we allowed male C57Bl/6 mice free access to a running wheel for 2 or 7 days. We injected bromodeoxyuridine (BrdU) before the last running night, respectively, and quantified cell proliferation with immunocytochemistry for BrdU and Ki-67. Furthermore, we performed immunocytochemistry for doublecortin (DCX) and real-time RT-qPCR for NeuroD1 to characterize and quantify changes in neurogenesis on the protein and mRNA level. Real-time RT-qPCR for neurogenic niche factors (BDNF, FGF-2, BMP4, Noggin) was used to detect changes in the molecular composition of the neurogenic niche. Interestingly, we observed that cell proliferation was already affected after 2 days of running showing a transient decrease, which was followed by a rebound with increased proliferation after 7 days. Neurogenesis was stimulated after 2 days of running, reflected by elevated NeuroD1 mRNA levels, and it was significantly increased after 7 days as indicated by DCX immunostaining. On the level of niche factors we observed changes in expression in favor of neuronal differentiation (increased BDNF mRNA expression) and proliferation (decreased BMP4 mRNA expression) already after 2 days, although increased proliferation is reflected on the cellular level only later. In summary, our data show that 2 days of running are sufficient to activate neurogenic processes and we hypothesize that a strong pressure toward differentiation privileges neurogenesis while proliferation lags behind

Genomic epidemiology of clinical ESBL-producing Enterobacteriaceae in a German hospital suggests infections are primarily community- and regionally-acquired

Clinical Enterobacteriaceae isolates that produce extended-spectrum β-lactamases (ESBLs) have been increasingly reported at a global scale. However, comprehensive data on the molecular epidemiology of ESBL-producing strains are limited and few studies have been conducted in non-outbreak situations. We used whole-genome sequencing to describe the population structure of 294 ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates that were recovered from a German community hospital throughout a 1 year sampling period in a non-outbreak situation. We found a high proportion of E. coli isolates (61.5 %) belonged to the globally disseminated extraintestinal pathogenic ST131, whereas a wider diversity of STs was observed among K. pneumoniae isolates. The E. coli ST131 population in this study was shaped by multiple introductions of strains as demonstrated by contextual genomic analysis including ST131 strains from other geographical sources. While no recent common ancestor of the isolates of the current study and other international isolates was found, our clinical isolates clustered with those previously recovered in the region. Furthermore, we found that the isolation of ESBL-producing clinical strains in hospitalized patients could only rarely be associated with likely patient-to-patient transmission, indicating primarily a community and regional acquisition of strains. Further genomic analyses of clinical, carriage and environmental isolates is needed to uncover hidden transmissions and thus discover the most common sources of ESBL-producing pathogen infections in our hospitals

Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window

Predator traits determine food-web architecture across ecosystems

Predator–prey interactions in natural ecosystems generate complex food webs that have a simple universal body-size architecture where predators are systematically larger than their prey. Food-web theory shows that the highest predator–prey body-mass ratios found in natural food webs may be especially important because they create weak interactions with slow dynamics that stabilize communities against perturbations and maintain ecosystem functioning. Identifying these vital interactions in real communities typically requires arduous identification of interactions in complex food webs. Here, we overcome this obstacle by developing predator-trait models to predict average body-mass ratios based on a database comprising 290 food webs from freshwater, marine and terrestrial ecosystems across all continents. We analysed how species traits constrain body-size architecture by changing the slope of the predator–prey body-mass scaling. Across ecosystems, we found high body-mass ratios for predator groups with specific trait combinations including (1) small vertebrates and (2) large swimming or flying predators. Including the metabolic and movement types of predators increased the accuracy of predicting which species are engaged in high body-mass ratio interactions. We demonstrate that species traits explain striking patterns in the body-size architecture of natural food webs that underpin the stability and functioning of ecosystems, paving the way for community-level management of the most complex natural ecosystems

Low frequency stimulation for seizure suppression: Identification of optimal targets in the entorhinal-hippocampal circuit

Background: Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) is a common form of drug-resistant focal epilepsy in adults. Treatment for pharmacoresistant patients remains a challenge, with deep brain stimulation (DBS) showing promise for alleviating intractable seizures. This study explores the efficacy of low frequency stimulation (LFS) on specific neuronal targets within the entorhinal-hippocampal circuit in a mouse model of MTLE. Objective: Our previous research demonstrated that LFS of the medial perforant path (MPP) fibers in the sclerotic hippocampus reduced seizures in epileptic mice. Here, we aimed to identify the critical neuronal population responsible for this antiepileptic effect by optogenetically stimulating presynaptic and postsynaptic compartments of the MPP-dentate granule cell (DGC) synapse at 1 Hz. We hypothesize that specific targets for LFS can differentially influence seizure activity depending on the cellular identity and location within or outside the seizure focus. Methods: We utilized the intrahippocampal kainate (ihKA) mouse model of MTLE and targeted specific neural populations using optogenetic stimulation. We recorded intracranial neuronal activity from freely moving chronically epileptic mice with and without optogenetic LFS up to 3 h. Results: We found that LFS of MPP fibers in the sclerotic hippocampus effectively suppressed epileptiform activity while stimulating principal cells in the MEC had no impact. Targeting DGCs in the sclerotic septal or non-sclerotic temporal hippocampus with LFS did not reduce seizure numbers but shortened the epileptiform bursts. Conclusion: Presynaptic stimulation of the MPP-DGC synapse within the sclerotic hippocampus is critical for seizure suppression via LFS

Short-term changes in bilateral hippocampal coherence precede epileptiform events.

International audienceThe mesial temporal lobe epilepsy syndrome (MTLE) is the most common form of focal epilepsies. MTLE patients usually respond very little to pharmacological therapy and surgical resection of temporal brain areas is mandatory. Finding less invasive therapies than resection of the sclerotic hippocampus requires knowledge of the network structures and dynamics involved in seizure generation. Investigation of the time interval immediately preceding seizure onset would help in understanding the initiation mechanisms of the seizure proper and, thereby, possibly improve therapeutical options. Here, we employed the in vivo intrahippocampal kainate model in mice, which is characterized by unilateral histological changes, resembling hippocampal sclerosis observed in human MTLE, and recurrent focal seizures. In these epileptic mice, population spikes occurred during epileptiform events (EEs) in the ipsilateral, histologically changed hippocampus, but also concomitantly in the contralateral, intact hippocampus. We studied synchronization processes between the ipsilateral, sclerotic hippocampus and the contralateral hippocampus immediately preceding the onset of EEs. We show that coherence between the two hippocampi decreased consistently and reliably for all EEs at 8 to 12 s before their onset at high frequencies (>100 Hz), without changes in power in these bands. This early decoupling of the two hippocampi indicates the time range for cellular and network mechanisms leading to increased excitability and/or synchronicity in the tissue and thus ultimately to epileptic seizures

Dentate gyrus and hilus transection blocks seizure propagation and granule cell dispersion in a mouse model for mesial temporal lobe epilepsy.

International audienceEpilepsy-associated changes of the anatomical organization of the dentate gyrus and hilus may play a critical role in the initiation and propagation of seizures in mesial temporal lobe epilepsy (MTLE). This study evaluated the role of longitudinal projections in the propagation of hippocampal paroxysmal discharges (HPD) in dorsal hippocampus by performing a selective transection in a mouse model for MTLE obtained by a single unilateral intrahippocampal injection of kainic acid (KA). Full transections of the dentate gyrus and hilus were performed in the transverse axis at 22 days after KA injection when spontaneous HPD were fully developed. They: (i) significantly reduced the occurrence of HPD; (ii) increased their duration at the KA injection site; (iii) abolished their spread along the longitudinal axis of the hippocampal formation and; (iv) limited granule cell dispersion (GCD) of the dentate gyrus posterior to the transection. These data suggest that: (i) longitudinal projections through the dentate gyrus and hilus are involved in HPD spread; (ii) distant hippocampal circuits participate in the generation and cessation of HPD and; (iii) GCD requires continuous HPD to develop, even when seizures are established. Our data reveal a critical role for longitudinal projections in the generation and spread of hippocampal seizures. © 2010 Wiley-Liss, Inc

Pseudomonas aeruginosa cupA-encoded fimbriae expression is regulated by a GGDEF and EAL domain-dependent modulation of the intracellular level of cyclic diguanylate.

Cyclic-diguanylate (c-di-GMP) is a widespread bacterial signal molecule that plays a major role in the modulation of cellular surface components, such as exopolysaccharides and fimbriae, and in the establishment of a sessile life style. Here, we report that intracellular c-di-GMP levels influence cupA-encoded fimbriae expression in Pseudomonas aeruginosa. In an autoaggregative P. aeruginosa small colony variant (SCV) CupA fimbriae and the intracellular c-di-GMP concentration were found to be enhanced as compared with the clonal wild-type. The SCV morphology and the expression of CupA fimbriae were dependent on a functional PA1120 and morA gene both encoding a GGDEF domain. Overexpression of the GGDEF domain protein PA1120 complemented the PA1120 and the morA mutant with respect to CupA fimbriae expression. In agreement with these findings, overexpression of the EAL domain containing phenotypic variance regulator (PvrR) in the SCV resulted in a decreased intracellular level of c-di-GMP, a reduced cupA fimbriae expression and a switch to wild-type colony morphology