bioRxiv Science⌕ Search

Biology subjects

Baud, O.

Publications and source records attributed to Baud, O..

4 recordsLinked to original sources

Minute- and second-scale hippocampal network dysfunctions in the 3xTgAD mouse model of Alzheimer's disease are prevented by TSPO knockout

The 18kDa translocator protein (TSPO) is widely recognized as a biomarker of neuroinflammation, but recent evidence suggests that it may also play a direct role in the pathophysiology of neurological conditions with an inflammatory component such as Alzheimers disease (AD). In this study, we leveraged functional ultrasound imaging (fUSi) to assess how TSPO knockout influences brain activity and connectivity in the 3xTgAD mouse model of AD. Resting-state scans were performed in 16-month-old male and female mice across four genotypes: WT, TSPO-/-, 3xTgAD or 3xTgAD.TSPO-/-. Using a data-driven approach, we identified key functional networks, including a bilateral hippocampal-amygdala limbic network. Dual regression analysis revealed increased engagement of the ventral hippocampus within the limbic network and elevated hemodynamic variance in 3xTgAD mice compared to WT. Moreover, co-activation patterns (CAPs) analysis showed abnormal activation/deactivation cycles involving the dorsal hippocampus, both of which were prevented by TSPO knockout without affecting amyloid or tau burden. Our findings highlight a functional role for TSPO in shaping network dynamics and suggest that its deletion can mitigate brain dysfunction in AD models.

neuroscience↗

Oxytocin release modulates acute neuroinflammation and improves brain development after pediatric traumatic brain injury

Pediatric traumatic brain injury (TBI) is a leading cause of death and disability early in life in infants, and its neurodevelopmental consequences cannot currently be effectively treated. Since TBI is associated with neuroinflammation, modulation of the post-injury neuroinflammatory response is a promising strategy. Oxytocin is thought to have anti-inflammatory properties and appears to play a role in clinical interventions that improve brain development in neonates. However, the underlying mechanisms remain unclear, as does its applicability to acute brain injury. Here we investigate the effects of chemogenetic modulation of endogenous oxytocin on acute neuroinflammation and on long-term brain development after TBI in postnatal day 7 (P7) male mice. We show that oxytocin release attenuates the acute neuroinflammatory response to TBI 24 hours after injury, by reducing the expression of immune- and inflammation-related genes in astrocytes and promoting gene pathways for brain repair and development in microglia. In the long term, oxytocin exposure ameliorates subcortical and cortical white matter damage after TBI, prevents hyperactivity and loss of social behavior, and restores TBI-induced alterations in resting-state functional connectivity of the isocortex. These findings enhance our understanding of the modulation of neuroinflammation and its long-term effects and support intervention related to endogenous oxytocin release as a promising neuroprotective strategy in pediatric TBI.

neuroscience↗

PhysiofUS : a tissue-motion based method for heart and breathing rate assessment in neurofunctional ultrasound imaging

Recent studies have shown growing evidence that brain function is closely synchronised with global physiological parameters. Heart rate is linked to various cognitive processes and previous research has also demonstrated a strong correlation between neuronal activity and breathing. These findings highlight the significance of monitoring these key physiological parameters during neuroimaging as they provide valuable insights into the overall brain function. Today, in neuroimaging, assessing these parameters required additional cumbersome devices or implanted electrodes. In this work, we performed ultrafast ultrasound imaging both in rodents and human neonates, and we extracted heart and breathing rates from local tissue motion assessed by raw ultrasound data processing. Such PhysiofUS automatically select two specific and optimal brain regions with pulsatile tissue signals to monitor such parameters. We validated the correspondence of these periodic signals with heart and breathing rates assessed using gold-standard electrodes in various conditions in rodents. We also validated Physio-fUS imaging in a clinical environment using conventional ECG. We show the potential of fUS imaging as an integrative tool for simultaneously monitoring physiological parameters during neurofunctional imaging. Beyond the technological improvement, this innovation could enhance our understanding of the link between breathing, heart rate and neurovascular activity both anesthetised in preclinincal research and clinical functional ultrasound imaging.

bioengineering↗

Oxytocin neurons mediates the effect of social isolation via the VTA circuits

Social interaction during adolescence strongly influences brain function and behaviour, and the recent pandemic has emphasized the devastating effect of social distancing on mental health. While accumulating evidences have shown the importance of the reward system in encoding specific aspects of social interaction, the consequences of social isolation on the reward system and the development of social skills later in adulthood are still largely unknown. Here, we found that one week of social isolation during adolescence in mice increased social interaction at the expense of social habituation and social novelty preference. Behavioural changes were accompanied by the acute hyperexcitability of dopamine (DA) neurons in the ventral segmental area (VTA) and long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto DA neurons that project to the prefrontal cortex (PFC). Social isolation-dependent behavioural deficits and changes in neural activity and synaptic plasticity were reversed by chemogenetic inhibition of oxytocin neurons in the paraventricular nucleus (PVN) of the hypothalamus. These results demonstrate that social isolation has acute and long-lasting effects on social interaction and suggest that these effects are mediated by homeostatic adaptations within the reward circuit.

neuroscience↗