Absence of the Peptide Transporter 1 Induces a Prediabetic and Depressive-Like Phenotype in Mice.

INTRODUCTION: Protein-enriched diets improve glycemic control in diabetes or emotional behavior in depressive patients. In mice, these benefits depend on intestinal gluconeogenesis activation by di-/tripeptides. Intestinal di-/tripeptides absorption is carried out by the peptide transporter 1, PEPT1. The lack of PEPT1 might thus alter glucose and emotional balance. METHODS: To determine the effects of PEPT1 deficiency under standard dietary conditions or during a dietary challenge known to promote both metabolic and cognitive dysfunction, insulin sensitivity, anxiety, and depressive-like traits, hippocampal serotonin (5-HT) and insulin signaling pathway were measured in wild-type (WT) and Pept1-/- mice fed either a chow or a high-fat high-sucrose (HF-HS) diet. RESULTS: Pept1-/- mice exhibited slight defects in insulin sensitivity and emotional behavior, which were aggravated by an HF-HS diet. Pept1-/- mice fed a chow diet had lower hippocampal 5-HT levels and exhibited cerebral insulin resistance under HF-HS diet. These defects were independent of intestinal gluconeogenesis but might be linked to increased plasma amino acids levels. CONCLUSION: Pept1-/- mice develop prediabetic and depressive-like traits and could thus be used to develop strategies to prevent or cure both diseases.

Working memory forgetting: Bridging gaps between human and animal studies.

The causes of forgetting in working memory (WM) remain a source of debate in cognitive psychology, partly because it has always been challenging to probe the complex neural mechanisms that govern rapid cognitive processes in humans. In this review, we argue that neural, and more precisely animal models, provide valuable tools for exploring the precise mechanisms of WM forgetting. First, we discuss theoretical perspectives concerning WM forgetting in humans. Then, we present neuronal correlates of WM in animals, starting from the initial evidence of delay activity observed in the prefrontal cortex to the later synaptic theory of WM. In the third part, specific theories of WM are discussed, including the notion that silent versus non-silent activity is more consistent with the processes of refreshing and decay proposed in human cognitive models. The review concludes with an exploration of the relationship between long-term memory and WM, revealing connections between these two forms of memory through the long-term synaptic hypothesis, which suggests that long-term storage of interference can potentially disrupt WM.