High-fat diet consumption increases hippocampal plasticity and affects performance in a spatial learning task in young female mice
Year: 2026
Type: article
Abstract: High-fat diet (HFD) consumption, a widespread dietary pattern in modern society, has been associated with an increased risk of cognitive impairments and psychiatric diseases. However, the underlying biological mechanisms remain poorly understood. This study aimed to identify early phenotypes of vulnerability to unhealthy dietary challenges emerging during adolescence and to elucidate the mechanisms through which HFD affects brain function. Spatial learning of female C57/Bl6 mice, fed a HFD enriched in omega-6 polyunsaturated fatty acids (PUFA) for five weeks, were tested in the IntelliCage system. Peripheral levels of adipokines and cytokines were measured by ELISA and LUMINEX, respectively. Electrophysiology and RNA sequencing analyses were used to evaluate hippocampal plasticity and transcriptomic changes. HFD consumption significantly increased body weight and leptin and reduced adiponectin blood concentrations. Interestingly, HFD enhanced hippocampal neuronal plasticity by increasing LTP amplitude in the CA1 region, and affected performance in a spatial learning task. Furthermore, HFD was associated with hippocampal transcriptional changes involving extracellular matrix remodeling and signaling pathways. In conclusion, these findings suggest that enhanced neural plasticity associated with preserved cognitive function may represent an early adaptive response to HFD exposure in females, potentially preceding later alterations in brain function. Further studies are needed to establish the temporal dynamics and sex dependence of these responses and to clarify their contribution to the complex effects of HFD on brain function.
Source: Scientific Reports
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7224095239