Biology subjects

Gibon, J.

Publications and source records attributed to Gibon, J..

4 recordsLinked to original sources

bioRxiv2024

Prenatal glyphosate exposure disrupts the gut-brain axis across several generations in mice.

Glyphosate, a widely used herbicide in North America, has become prevalent in the food supply, raising concerns about potential health impacts. In this exploratory study, male and female F0 mice were exposed to glyphosate through drinking water during mating and gestation. We investigated whether prenatal exposure at dietary-relevant levels (0.01 mg/kg/day, Average American Diet, [AAD]) or the U.S. EPAs acceptable daily intake (1.75 mg/kg/day, [EPA upper limit]) altered gut, metabolic, and behavioral outcomes across two generations in mice with or without genetic susceptibility to colitis (Muc2+/- and Muc2-/-, respectively). Healthy (Muc2+/-) offspring of glyphosate-exposed mice exhibited colonic goblet cell depletion, reduced mucin-2 expression, and pro-inflammatory cytokine profiles in both F1 and F2 generations. These healthy (Muc2+/-) offspring also developed metabolic dysfunction, including impaired glucose tolerance, insulin resistance, and reduced GLP-1 in serum. Behavioral deficits were also observed in healthy (Muc+/-) mice including reduced locomotion and working memory, and these changes were associated with altered microbiome composition and gut-brain mediators. These findings suggest that prenatal glyphosate exposure, even below regulatory thresholds, may disrupt multiple physiological systems across generations, highlighting the need for further research and regulatory consideration.

pharmacology and toxicology↗

bioRxiv2021

PITA, a pre-bilaterian p75NTR, is the evolutionary ancestor of TNF receptors

Tumor necrosis factor receptors (TNFRs) regulate a diverse array of biological functions, including adaptive immunity, neurodevelopment, and many others. Although TNFRs are expressed in all metazoan phyla, a coherent model of the molecular origins of mammalian TNFRs--and how they relate to TNFRs in other phyla--has remained elusive. To address this, we executed a large-scale, systematic Basic Local Alignment Search Tool (BLAST)-based approach to trace the evolutionary ancestry of all 29 human TNFRs. We discovered that all human TNFRs are descendants of a single pre-bilaterian TNFR with strong sequence similarity to the p75 neurotrophin receptor (p75NTR), which we designate as PITA for p75NTR is the TNFR Ancestor. A distinct subset of human TNFRs--including EDAR, XEDAR and TROY--share a unique history as descendants of EDAR-XEDAR-TROY (EXT), which diverged from PITA in a bilaterian ancestor. Most PITA descendants possess a death domain (DD) within their intracellular domain (ICD) but EXTs do not. PITA descendants are expressed in all bilaterian phyla and Cnidaria, but not in non-planulozoan ParaHoxozoa, suggesting that PITA originated in an ancestral planulozoan. Drosophila melanogaster TNFRs (Wengen (Wgn) and Grindelwald (Grnd)) were identified as divergent PITA descendants, providing the first evolutionary link between this model TNFR system and the mammalian TNFR superfamily. This study reveals PITA as the ancestor to human and Drosophila TNFR systems and describes an evolutionary model that will facilitate deciphering TNF-TNFR functions in health and disease.

evolutionary biology↗

bioRxiv2021

Aminooxadiazolyl kainic acid reveals that kainic acid receptors contribute to astrocytoma glutamate signaling

The excitatory neurotransmitter glutamate triggers a Ca2+ rise and the extension of processes in astrocytes. Our results suggest that kainic acid receptors (KAR) can independently initiate glutamate signaling in astrocytoma U118-MG cells. The natural product kainic acid triggered glioexcitablity in cells and was inhibited by the KAR antagonist CNQX, but its activity was lower than glutamate on KARs. We created a new heteroaryl kainoid based on rational design: aminooxadiazolyl kainic acid 1 (AODKA). AODKA induced a larger calcium influx and a faster processes extension than kainic acid in U118-MG cells. AODKA is a new tool to study KAR activity in the nervous system. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/426948v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1b63f72org.highwire.dtl.DTLVardef@1ff92c4org.highwire.dtl.DTLVardef@1fcb212org.highwire.dtl.DTLVardef@10ed76e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus.

Dynamic trafficking of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.

neuroscience↗