Biology subjects

Bennis, M.

Publications and source records attributed to Bennis, M..

5 recordsLinked to original sources

bioRxiv2026

Rat mediodorsal thalamic subdivisions differentially modulate the sensory and affective components of pain through distinct prefrontal pathways.

The mediodorsal thalamus (MD) modulates pain through thalamocortical regulation of the mPFC. Yet, MD is often treated as a single anatomical and functional entity despite marked internal heterogeneity. Here, we tested whether medial-central MD (MDmc) and lateral MD (MDl) subdivisions exert dissociable control over sensory-discriminative and affective-motivational components of pain by engaging the anterior cingulate cortex (ACC) and prelimbic cortex (PrL). Using subdivision-selective excitotoxic lesions in rats, combined with anterograde tracing, laminar activity mapping, and projection-specific optogenetic manipulation of MDmc and MDl terminals in ACC or PrL, we determined the contribution of each subdivision and the underlying MD-PFC circuit mechanisms. Behaviorally, MDmc and MDl lesions induced mechanical and thermal hypersensitivity, but only MDmc lesions increased pain-related avoidance. Anatomical analyses showed that MDl preferentially innervated ACC PV cells, whereas MDmc more strongly targeted ACC SOM cells. Lesions further produced subdivision-dependent reorganization of nociception-evoked cFos activity in layers 2/3 and 5 and altered PV/SOM interneuron recruitment. Optogenetic manipulations revealed pathway-specific effects: MDmc-ACC/PrL manipulations enhanced nociceptive gain and avoidance, whereas MDl-ACC inhibition increased hypersensitivity while reducing avoidance, and MDl-PrL inhibition increased both nociceptive sensitivity and avoidance. Together, these findings identify MD subdivision-specific thalamocortical pathways that recruit distinct inhibitory microcircuits within ACC and PrL, thereby differentially shaping sensory-discriminative and affective-motivational components of pain.

neuroscience↗

bioRxiv2026

A newly identified detoxification system protects uropathogenic Escherichia coli from reactive chlorine species

Neutrophils eliminate invading pathogens through the production of reactive oxygen and chlorine species (ROS/RCS), with hypochlorous acid (HOCl) representing the most abundant and bactericidal oxidant produced in this process. Compared to bacterial defenses against ROS, which are well studied, little is known about how pathogens respond to and counter RCS, including HOCl. Here, we identify and mechanistically characterize RcrB, a protein of the uncharacterized DUF417 protein family, for which no role in oxidative stress defense has been described yet. We report a previously unrecognized role as an RCS detoxification system that confers high-level resistance to uropathogenic Escherichia coli (UPEC). We show that RcrB is an inner membrane protein and strongly induced during RCS exposure and phagocytosis. Loss of RcrB results in profound HOCl hypersensitivity, accompanied by elevated macromolecular damage and severe metabolic perturbations, establishing RcrB as a central determinant of UPECs RCS stress resistance. Heterologous expression of RcrB in HOCl-sensitive intestinal E. coli strains is sufficient to restore resistance but requires functional glutathione biosynthesis. Quantitative HOCl trapping assays demonstrate that RcrB expression protects the bacterial population by significantly reducing extracellular HOCl, indicating active chemical quenching rather than passive membrane protection. Structure-function analysis of RcrB confirms this conclusion and demonstrate that conserved, redox-active amino acids facing the periplasm are essential for its detoxification activity. In summary, our study reveals a hitherto unknown bacterial strategy for mitigating RCS and reveal a distinct mechanism by which UPEC may survive the mammalian host defense. Significance StatementDuring infection, human immune cells such as neutrophils kill bacteria by releasing powerful oxidants, including hypochlorous acid (HOCl), the active ingredient of household bleach. How pathogenic bacteria survive this chemical attack is still poorly understood. This study identifies a membrane protein in uropathogenic Escherichia coli as a key defense factor that neutralizes HOCl before it can damage the cell. RcrB acts at the bacterial cell envelope, where it detoxifies HOCl in a glutathione-dependent manner to maintain a balanced redox homeostasis and cellular integrity, thereby even protect neighboring bacteria. These findings reveal a previously unrecognized frontline defense strategy that helps pathogens survive immune attack and may represent a new target for antimicrobial therapies.

microbiology↗

bioRxiv2023

Expression of RcrB confers resistance to hypochlorous acid in uropathogenic Escherichia coli

To eradicate bacterial pathogens, neutrophils are recruited to the sites of infection, where they engulf and kill microbes through the production of reactive oxygen and chlorine species (ROS/RCS). The most prominent RCS is antimicrobial oxidant hypochlorous acid (HOCl), which rapidly reacts with various amino acids side chains, including those containing sulfur and primary/tertiary amines, causing significant macromolecular damage. Pathogens like uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections (UTIs), have developed sophisticated defense systems to protect themselves from HOCl. We recently identified the RcrR regulon as a novel HOCl defense strategy in UPEC. The regulon is controlled by the HOCl-sensing transcriptional repressor RcrR, which is oxidatively inactivated by HOCl resulting in the expression of its target genes, including rcrB. rcrB encodes the putative membrane protein RcrB, deletion of which substantially increases UPECs susceptibility to HOCl. However, many questions regarding RcrBs role remain open including whether (i) the proteins mode of action requires additional help, (ii) rcrARB expression is induced by physiologically relevant oxidants other than HOCl, and (iii) expression of this defense system is limited to specific media and/or cultivation conditions. Here, we provide evidence that RcrB expression is sufficient to E. colis protection from HOCl and induced by and protects from several RCS but not from ROS. RcrB plays a protective role for RCS-stressed planktonic cells under various growth and cultivation conditions but appears to be irrelevant for UPECs biofilm formation. IMPORTANCEBacterial infections pose an increasing threat to human health exacerbating the demand for alternative treatment options. UPEC, the most common etiological agent of urinary tract infections (UTIs), are confronted by neutrophilic attacks in the bladder, and must therefore be well equipped with powerful defense systems to fend off the toxic effects of RCS. How UPEC deal with the negative consequences of the oxidative burst in the neutrophil phagosome remains unclear. Our study sheds light on the requirements for the expression and protective effects of RcrB, which we recently identified as UPECs most potent defense system towards HOCl-stress and phagocytosis. Thus, this novel HOCl-stress defense system could potentially serve as an attractive drug target to increase the bodys own capacity to fight UTIs.

microbiology↗

bioRxiv2019

Neurons expressing pathological Tau protein trigger dramatic noninflammatory changes in microglial morphology and dynamics

Microglial cells, the resident macrophages of the brain, are important players in the pathological process of numerous neurodegenerative disorders, including tauopathies, a heterogeneous class of diseases characterized by intraneuronal Tau aggregates. However, microglia response in Tau pathologies remains poorly understood. Here we exploit a genetic zebrafish model of tauopathy, combined with live microglia imaging, to investigate the behaviour of microglia in vivo in the disease context. Results show that while microglia were almost immobile and displayed long and highly dynamic branches in a wild-type context, in presence of diseased neurons cells became highly mobile and displayed morphological changes, with highly mobile cell bodies together with fewer and shorter processes. We also imaged, for the first time to our knowledge, the phagocytosis of apoptotic tauopathic neurons by microglia in vivo and observed that microglia engulfed about as twice materials as in controls. Finally, genetic ablation of microglia in zebrafish tauopathy model significantly increased Tau hyperphosphorylation, suggesting that microglia provide neuroprotection to diseased neurons. Our findings demonstrate for the first time the dynamics of microglia in contact with tauopathic neurons in vivo and open perspectives for the real-time study of microglia in many neuronal diseases.

neuroscience↗

bioRxiv2017

On the difficulty to interpret results when animals are singly housed: experimental epilepsy as a prototypical example

Many experimental approaches require housing rodents in individual cages, including in epilepsy research. However, rats and mice are social animals; and individual housing constitutes a stressful situation. The goal of the present study was to determine the effects of individual housing as compared to conditions maintaining social contact on stress markers and epilepsy. Control male mice socially housed during pretest and then transferred to individual cages for six weeks displayed anhedonia, increased anxiety and biological markers of stress as compared to pretest values or mice kept socially housed during six weeks. Pilocarpine-treated mice housed together showed increased levels of anhedonia, anxiety and stress markers as well as decreased cognitive performance as compared to the control group. The differences were more significant in pilocarpine-treated mice housed individually. Anxiety correlated linearly with cognitive performance and stress markers independently of the experimental conditions. In the male rat pilocarpine model, seizures were sixteen times more frequent in singly housed animals as compared to animals kept in pairs. Daily interactions with an experimenter in otherwise singly housed animals was sufficient to produce results identical to those found in animals kept in pairs. We propose that social isolation produces a severe phenotype in terms of stress and seizure frequency as compared to animals maintaining social contact (at least in these two models), a factor that needs to be taken into account for data interpretation, in particular for preclinical studies.\n\nSignificance StatementMany experimental approaches require housing rodents in individual cages, a stressful condition for social animals, even in an enriched environment context. Using the pilocarpine model of epilepsy in rats and mice, we report that singly housing animals develop a more severe phenotype in terms of stress and epilepsy as compared to animals maintaining social contact. We propose that social isolation adds a degree of complexity for the interpretation of data, which may be particularly relevant for preclinical studies.

neuroscience↗