Biology subjects

Badaut, J.

Publications and source records attributed to Badaut, J..

5 recordsLinked to original sources

bioRxiv2025

Brain-blood biomarkers take a walk on the wild side: glial responses to environmental conditions and individual traits in wild frogs

Proteins from brain cells, including Glial fibrillary acidic protein (GFAP), has been tested for diagnostic and prognostic of neurological dysfunctions. Release of GFAP into the blood-stream, may be a consequence of its up-regulation in reactive astrocytes. However, astrocytic-GFAP expression is also increased during brain remodeling after physiological perturbations such as osmotic challenge. The presence and quantification of GFAP in blood circulation have never been investigated in the context of brain responses to environmental variations in wildlife. In a wild amphibian (green frogs, Pelophylax sp.), captured in several ponds with different salinity, GFAP was detected in plasma. Males from more saline ponds exhibited higher plasmatic GFAP levels, independent to their blood osmolality, suggesting that plasmatic GFAP-level reflects cerebral response to osmotic challenge. Plasmatic-GFAP correlated with immune markers (hemoglobin binding proteins, lymphocytes, neutrophils and monocytes), size and body condition, reinforcing its role as a physiological biomarker. We also highlighted that captivity had a significant effect on plasmatic-GFAP levels with sex-specific dynamics, masking the response to a short-term experimental salinity exposure. For the very first time, we show that plasmatic-GFAP levels could be a biomarker of brain plasticity to environmental conditions, physiological traits, and stress responses in wildlife. Significant StatementWe investigated the use of brain Glial fibrillary acidic protein (GFAP), a cytoskeletal protein of astrocytes, that has been associated with brain disorders in clinical studies, as a biomarker of environmental conditions and individual traits in wildlife. In a wild amphibian, plasmatic GFAP-levels were correlated with the salinity of ponds, immune markers and size for males. GFAP-levels were correlated with body condition for both sexes. Interestingly, captivity induced transient increase of plasmatic-GFAP levels, probably due to stress. In our study, we demonstrate that plasmatic-GFAP levels may represent an excellent brain biomarker of its plasticity to environmental conditions, physiological traits, and stress responses in wildlife.

physiology↗

bioRxiv2024

Endocannabinoid-mediated rescue of somatosensory cortex activity, plasticity and related behaviors following an early in life concussion.

Due to the assumed plasticity of immature brain, early in life brain alterations are thought to lead to better recoveries in comparison to the mature brain. Despite clinical needs, how neuronal networks and associated behaviors are affected by early in life brain stresses, such as pediatric concussions, have been overlooked. Here we provide first evidence in mice that a single early in life concussion durably increases neuronal activity in the somatosensory cortex into adulthood, disrupting neuronal integration while the animal is performing sensory-related tasks. This represents a previously unappreciated clinically relevant mechanism for the impairment of sensory-related behavior performance. Furthermore, we demonstrate that pharmacological modulation of the endocannabinoid system a year post-concussion is well-suited to rescue neuronal activity and plasticity, and to normalize sensory-related behavioral performance, addressing the fundamental question of whether a treatment is still possible once post-concussive symptoms have developed, a time-window compatible with clinical treatment.

neuroscience↗

bioRxiv2023

Progressive lifespan modifications in the corpus callosum following a single juvenile concussion in male mice monitored by diffusion MRI

IntroductionThe sensitivity of white matter (WM) in acute and chronic moderate-severe traumatic brain injury (TBI) has been established. In concussion syndromes, particularly in preclinical rodent models, there is lacking a comprehensive longitudinal study spanning the lifespan of the mouse. We previously reported early modifications to WM using clinically relevant neuroimaging and histological measures in a model of juvenile concussion at one month post injury (mpi) who then exhibited cognitive deficits at 12mpi. For the first time, we assess corpus callosum (CC) integrity across the lifespan after a single juvenile concussion utilizing diffusion MRI (dMRI). MethodsC57Bl/6 mice were exposed to sham or two severities of closed-head concussion (Grade 1, G1, speed 2 m/sec, depth 1mm; Grade 2, G2, 3m/sec, 3mm) using an electromagnetic impactor at postnatal day 17. In vivo diffusion tensor imaging was conducted at 1, 3, 6, 12 and 18 mpi (21 directions, b=2000 mm2/sec) and processed for dMRI parametric maps: fractional anisotropy (FA), axial (AxD), radial (RD) and mean diffusivity (MD). Whole CC and regional CC data were extracted. To identify the biological basis of altered dMRI metrics, astrocyte and microglia in the CC were characterized at 1 and 12 mpi by immunohistochemistry. ResultsWhole CC analysis revealed altered FA and RD trajectories following juvenile concussion. Shams exhibited a temporally linear increase in FA with age while G1/G2 mice had plateaued FA values. G2 concussed mice exhibited high variance of dMRI metrics at 12mpi, which was attributed to the heterogeneity of TBI on the anterior CC. Regional analysis of dMRI metrics at the impact site unveiled significant differences between G2 and sham mice. The dMRI findings appear to be driven, in part, by loss of astrocyte process lengths and increased circularity and decreased cell span ratios in microglia. ConclusionFor the first time, we demonstrate progressive perturbations to WM of male mice after a single juvenile concussion across the mouse lifespan. The CC alterations were dependent on concussion severity with elevated sensitivity in the anterior CC that was related to astrocyte and microglial morphology. Our findings suggest that long-term monitoring of children with juvenile concussive episodes using dMRI is warranted, focusing on vulnerable WM tracts.

neuroscience↗

bioRxiv2022

A single mild juvenile TBI in mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age in male mice

Traumatic brain injury (TBI) has the highest incidence amongst the pediatric population and its mild severity represents the most frequent cases. Moderate and severe injuries as well as repetitive mild TBI result in lasting morbidity. However, whether a single mild TBI sustained during childhood can produce long-lasting modifications within the brain is still debated. We aimed to assess the consequences of a single juvenile mild TBI (jmTBI) at 12 months post-injury in a mouse model. Non-invasive diffusion tensor imaging (DTI) revealed significant microstructural alterations in the hippocampus and the in the substantia innominata/nucleus basalis (SI/NB), structures known to be involved in spatial learning and memory. DTI changes paralled neuronal loss, increased astrocytic AQP4 and microglial activation in the hippocampus. In contrast, decreased astrocytic AQP4 expression and microglia activation were observed in SI/NB. Spatial learning and memory were impaired and correlated with alterations in DTI-derived derived fractional ansiotropy (FA) and axial diffusivity (AD). This study found that a single juvenile mild TBI leads to significant region-specific DTI microstructural alterations, distant from the site of impact, that correlated with cognitive discriminative novel object testing and spatial memory impairments at 12 months after a single concussive injury. Our findings suggest that exposure to jmTBI leads to a chronic abnormality, which confirms the need for continued monitoring of symptoms and the development of long-term treatment strategies to intervene in children with concussions.

neuroscience↗

bioRxiv2019

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our results show that maternal dietary n-3 PUFA deficiency increases microglial phagocytosis of synaptic elements in the developing hippocampus, through the activation of 12/15- lipoxygenase (LOX)/12-HETE signaling, which alters neuronal morphology and affects cognition in the postnatal offspring. While women of child bearing age are at higher risk of dietary n-3 PUFA deficiency, these findings provide new insights into the mechanisms linking maternal nutrition to neurodevelopmental disorders.\n\nOne Sentence SummaryLow maternal omega-3 fatty acids intake impairs microglia-mediated synaptic refinement via 12-HETE pathway in the developing brain.

neuroscience↗