No abstract

A hypercaloric diet given to adolescent rats induces social memory deficits and reduced neurochemical markers of normal social development.

No abstract

No abstract

The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.

Obesity and high fat diet consumption contribute to the development of metabolic disorders, insulin resistance, neuroinflammation, and cognitive impairments. CNS administration of insulin into the brain can attenuate these cognitive impairments. The present study investigated whether hippocampal-dependent spatial memory impairments in a dietary induced mouse model of obesity could be improved by the direct administration of insulin into the hippocampus and whether this was associated with markers of hippocampal inflammation. C57Bl/6J mice consumed a low fat or high fat diet for 16 weeks and continuous intrahippocampal saline or insulin infusion for the final 4 weeks, during a period of behavioral testing, before gene expression analysis was performed. The high fat diet group demonstrated poorer spatial memory performance in the Morris water maze and Y-maze, supporting the hypothesis that high fat diet leads to hippocampal dependent cognitive impairment. Insulin infusion into the hippocampus reversed the deficit of high fat diet consumption on both of the tasks. Increased expression of inflammatory markers was detected in the hippocampus in the high fat diet group and expression of these markers was ameliorated in insulin infused mice. This demonstrates that CNS insulin can improve hippocampal-dependent memory and that hippocampal inflammation may be a factor in the development of cognitive deficits associated with diet-induced obesity. Furthermore, these data suggest that insulin may act to attenuate high fat diet induced cognitive deficits by reducing neuroinflammation.

Excessive consumption of high fat and high sugar (HFHS) diets are known to alter reward processing and aspects of behaviour, and change microbiota profiles. Studies in gnotobiotic mice also provide evidence that gut microorganisms influence social behaviour. To further investigate these interactions, the impact of intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition was examined. Rats were permitted intermittent daily access (2h / day) to a palatable HFHS diet for 28 days across the adolescent period. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa. Reduced social interaction behaviours, and impaired social memory and novel object recognition were observed in HFHS diet rats. Reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA were observed in the PFC of HFHS diet rats. The relative abundance of a number of specific taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria, which also predicted social behaviours, novel object recognition performance and Maoa expression. This is the first study to show that limited daily access to HFHS diet alters social behaviour and cognition in rats. Furthermore, behavioural changes are associated with alterations to cortical gene expression of enzymes involved in monoamine synthesis and neuroplasticity, and microbiota profiles predicted diet-induced changes to behaviour and gene expression.

Insulin is known to act in the central nervous system to regulate several physiological and behavioural outcomes, including energy balance, glucose homeostasis and cognitive functioning. However, the neuronal populations through which insulin enhances cognitive performance remain unidentified. Insulin receptors are found in neuropeptide-Y (NPY) expressing neurons, which are abundant in the hypothalamus and hippocampus; regions involved in feeding behaviour and spatial memory, respectively. Here we show that mice with a tissue specific knockout of insulin receptors in NPY expressing neurons (IR lox/lox ; NPY Cre/+ ) display an impaired performance in the probe trial of the Morris Water Maze compared with control mice at both the 6 and the 12, but not at the 24 months time point, consistent with a crucial role of insulin and NPY in cognitive functioning. By 24 months of age all groups demonstrated similar reductions in spatial memory performance. Together, these data suggest that the mechanisms through which insulin in luences cognitive functioning are, at least in part, via insulin receptor signaling in NPY expressing neurons. These results also highlight that cognitive impairments observed in aging may be due to impaired insulin signaling.