de La Serre, C. | Search bioRxiv

bioRxiv2025

Endotoxemia-induced inflammation in the absence of obesity decreases anxiety-like and impulsive behavior without affecting learning and memory

Obesity is associated with increased gut permeability, which contributes to a state of chronic low-grade inflammation. Obesity is also linked with altered neurocognitive functions, including impaired learning and memory. Whether these changes are secondary to neuroinflammation vs. other comorbidities associated with obesity is unknown. Here, we modeled the chronic low-grade inflammation that accompanies diet-induced obesity, but in the absence of obesity or consumption of an obesogenic diet. Male rats were implanted with intraperitoneal osmotic minipumps, continuously dispensing either saline (control) or lipopolysaccharide (LPS), an endotoxin produced in the gut that triggers inflammation when in circulation. Immunohistochemistry results revealed that LPS exposure led to neuroinflammation, with an increased number of Ionized Calcium-Binding Molecule 1 (Iba1+) cells in the amygdala and hippocampus in LPS rats vs. controls. Given that these brain regions are associated with impulse control, anxiety-like behavior, and learning and memory, we tested whether chronic LPS treatment impacted these behaviors. Interestingly, LPS exposure did not affect hippocampal-dependent memory in the Morris water maze, novel location recognition, or novel object in context memory tests, suggesting that neuroinflammation in the absence of obesity does not induce memory impairments. Further, chronic LPS significantly decreased anxiety-like behavior in the open field test and food impulsivity in an operant-based procedure. LPS animals also had significantly lower corticosterone and melatonin levels when compared to controls, which may contribute to these behavioral outcomes. These results suggest that the low-grade inflammation associated with obesity is not driving obesity-associated memory impairments but does reduce anxiety and food-motivated impulsive responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/654970v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@788648org.highwire.dtl.DTLVardef@b7fce8org.highwire.dtl.DTLVardef@13cf526org.highwire.dtl.DTLVardef@102c19c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

The gut microbiome regulates memory function

Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genus Parabacteroides (P. distasonis and P. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereas Parabacteroides microbial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota "dysbiosis" in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.

neuroscience↗