Biology subjects

Bernanos, M.

Publications and source records attributed to Bernanos, M..

4 recordsLinked to original sources

bioRxiv2025

Complement receptor C3ar1 deficiency does not alter brain structure or functional connectivity across early life development

Genetic deletion of the complement C3a anaphylatoxin chemotactic receptor (C3ar1), a key component of the innate immune response, is reported to induce behavioural phenotypes consistent with psychiatric symptomatology in mice, but when and where C3ar1 is needed in the brain is unresolved. These questions are significant because, as a G-protein-coupled receptor, human C3AR1 serves as a potential therapeutic target for disorders associated with complement dysregulation, such as schizophrenia. To provide a brain-wide (where) assessment of developmental C3ar1 activity, we used longitudinal (when) tensor-based morphometry, diffusion-weighted magnetic resonance imaging (MRI) and blood oxygen-level dependent functional MRI in male and female C3ar1-deficient mice and wild-type littermates, with behavioural assessment in adulthood. Unexpectedly, we did not find a robust C3ar1-dependent phenotype in any of these measures. Therefore, our study does not support neurodevelopmental hypotheses for C3ar1, which is encouraging for therapeutic strategies targeting this receptor since interventions are unlikely to disrupt brain development.

neuroscience↗

bioRxiv2022

Individual behavioral trajectories shape whole-brain connectivity in mice

It is widely assumed that our actions shape our brains and that the resulting connections determine who we are. To test this idea in a reductionist setting, in which genes and environment are controlled, we investigated differences in neuroanatomy and structural covariance by ex vivo structural magnetic resonance imaging (MRI) in mice whose behavioral activity was continuously tracked for 3 months in a large, enriched environment. We confirmed that environmental enrichment increases mouse hippocampal volumes. Stratifying the enriched group according to individual longitudinal behavioral trajectories, however, revealed striking differences in mouse brain structural covariance in continuously highly active mice compared to those whose trajectories showed signs of habituating activity. Network-based statistics identified distinct sub-networks of murine structural covariance underlying these differences in behavioral activity. Together, these results reveal that differentiated behavioral trajectories of mice in an enriched environment are associated with differences in brain connectivity.

neuroscience↗

bioRxiv2021

Dispersed Sleep Microstates and Associated Structural Changes in GBA1 Mouse: Relevance to Rapid Eye Movement Behavior Disorder

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a rare parasomnia that may predict the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of -synucleinopathy, we now demonstrate striking REM and NREM sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.

neuroscience↗

bioRxiv2018

Corticospinal neuroplasticity and sensorimotor recovery in rats treated by infusion of neurotrophin-3 into disabled forelimb muscles started 24 h after stroke

Stroke often leads to arm disability and reduced responsiveness to stimuli on the other side of the body. Neurotrophin-3 (NT3) is made by skeletal muscle during infancy but levels drop postnatally and into adulthood. It is essential for the survival and wiring-up of sensory afferents from muscle. We have previously shown that gene therapy delivery of human NT3 into the affected triceps brachii forelimb muscle improves sensorimotor recovery after ischemic stroke in adult and elderly rats. Here, to move this therapy one step nearer to the clinic, we set out to test the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after ischemic cortical stroke in adult rats. To simulate a clinically-feasible time-to-treat, twenty-four hours later rats were randomized to receive NT3 or vehicle by infusion into triceps brachii for four weeks using implanted minipumps. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory deficits on the affected forearm. There was no evidence of forepaw sensitivity to cold stimuli after stroke or NT3 treatment. MRI confirmed that treatment did not induce neuroprotection. Functional MRI during low threshold electrical stimulation of the affected forearm showed an increase in peri-infarct BOLD signal with time in both stroke groups and indicated that neurotrophin-3 did not further increase peri-infarct BOLD signal. Rather, NT3 induced spinal neuroplasticity including sprouting of the spared corticospinal and serotonergic pathways. Neurophysiology showed that NT3 treatment increased functional connectivity between the corticospinal tracts and spinal circuits controlling muscles on the treated side. After intravenous injection, radiolabelled NT3 crossed from bloodstream into the brain and spinal cord in adult mice with or without strokes. Our results show that delayed, peripheral infusion of neurotrophin-3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral, high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke.

neuroscience↗