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Recent biochemical and behavioural evidence indicates that metabolic hormones not only regulate energy intake and nutrient content, but also modulate plasticity and cognition in the central nervous system. Disruptions in metabolic hormone signalling may provide a link between metabolic syndromes like obesity and diabetes, and cognitive impairment. For example, altered metabolic homeostasis in obesity is a strong determinant of the severity of age-related cognitive decline and neurodegenerative disease. Here we review the evidence that eating behaviours and metabolic hormones-particularly ghrelin, leptin, and insulin-are key players in the delicate regulation of neural plasticity and cognition. Caloric restriction and antidiabetic therapies, both of which affect metabolic hormone levels can restore metabolic homeostasis and enhance cognitive function. Thus, metabolic hormone pathways provide a promising target for the treatment of cognitive decline., (Copyright © 2022. Published by Elsevier Inc.)

Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet. The HFHS-fed rats displayed diet-induced changes in prefrontal cortex (PFC) function which were detected by altered expression of GABAergic parvalbumin-expressing inhibitory interneurons and the stable transcription factor ΔFosB which accumulates in the PFC in response to chronic stimuli. Immunohistochemical analyses of the medial PFC revealed that animals fed the HFHS diet had fewer parvalbumin-expressing cells and increased levels of FosB/ΔFosB expression in the infralimbic cortex, a region implicated in the consolidation of fear extinction. There was a trend towards increased IBA-1 immunoreactivity, a marker of microglial activation, in the infralimbic cortex after HFHS diet exposure but expression of the extracellular glycoprotein reelin was unaffected. These findings demonstrate that a HFHS diet during adolescence is associated with reductions of prefrontal parvalbumin neurons and impaired fear inhibition in adulthood. Adverse effects of HFHS diets on the mechanisms of fear regulation may precipitate a vulnerability in obese individuals to the development of anxiety disorders., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Frontotemporal lobe dementia (FTD) is a heterogeneous range of disorders, a subset of which arise from fully penetrant, autosomal dominant point mutations in the gene coding for the microtubule associated protein tau. These genetic tauopathies are associated with complex behavioural/cognitive disturbances, including compromised executive function. In the present study, we modelled the effects of the FTD with Parkinsonism linked to chromosome 17 (FTDP-17) tauV337M mutation (known as the Seattle Family A mutation) expressed in mice on executive processes using a novel murine analogue of the Stroop task. Employing biconditional discrimination procedures, Experiment 1 showed that normal mice, but not mice with excitotoxic lesions of the medial prefrontal cortex, were able to use context cues to resolve response conflict generated by incongruent stimulus compounds. In contrast to predictions, response conflict resolution was not disrupted by the tauV337M mutation (Experiment 2). However, while context appropriate actions were goal-directed in wild-type mice, performance of tauV337M mice was not goal-directed (Experiment 3). The results indicate that the tauV337M mutation in mice disrupts, selectively, a subset of processes related to executive function., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Instrumental performance in rats with hippocampal lesions is insensitive to the degradation of action-outcome contingencies, but sensitive to the effects of selective devaluation by satiation. One interpretation of this dissociation is that damage to the hippocampus impairs the formation of context-outcome associations upon which the effect of contingency degradation, but not selective satiation, relies. Here, we provide a direct assessment of this interpretation, and showed that conditioned responding to contexts did not show sensitivity to selective satiation (Experiment 1), and confirmed that instrumental performance was sensitive to selective satiation (Experiment 2) following hippocampal cell loss., (Copyright © 2011 Elsevier Inc. All rights reserved.)