Amy P. Ross

Non-alcoholic fatty liver disease impairs hippocampal-dependent memory in male rats.

Non-alcoholic fatty liver disease (NAFLD) is a disorder observed in children and adults characterized by an accumulation of liver fat (>5% wet weight) in the absence of excessive alcohol intake. NAFLD affects 10 to 30% of the American population and is the most common cause of liver disease in the United States. NAFLD leads to serious disturbances in cardiovascular and hormonal function; however, possible effects on brain function have been overlooked. The aims of the present study were to test whether diet-induced NAFLD impairs hippocampal-dependent memory and to determine whether any observed deficits are associated with changes in hippocampal insulin signaling or concentrations of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). Post-weanling male Sprague-Dawley rats were fed a high fructose (60% of calories) or control diet for 12 weeks and then trained and tested in a spatial water maze. NAFLD was confirmed with postmortem measures of liver mass and liver lipid concentrations. NAFLD did not affect acquisition of the spatial water maze, but did impair retention tested 48 h later. Specifically, both groups demonstrated similar decreases in latency to swim to the escape platform over training trials, but on the memory test NAFLD rats took longer to reach the platform and made fewer visits to the platform location than control diet rats. There were no differences between the groups in terms of insulin-stimulated phosphorylation of insulin receptor β subunit (IR-β) and protein kinase B (PKB/AKT) in hippocampal slices or hippocampal BDNF or IGF-1 concentrations. Thus, these data indicate that NAFLD impairs hippocampal-dependent memory function and that the deficit does not appear attributable to alterations in hippocampal insulin signaling or hippocampal BDNF or IGF-1 concentrations.

Predicting the effects of a high‐energy diet on fatty liver and hippocampal‐dependent memory in male rats

In rodents, diets exceeding nutritional requirements (i.e., high‐energy diets; HED) impair hippocampal‐dependent memory. Our research suggests that the effects likely involve HED‐induced increases in liver lipids. In this experiment, rats were provided with diet choices to test whether voluntary consumption of a HED impairs spatial memory, whether differences in initial weight gain predict memory deficits, and whether increases in liver lipids are associated with the memory deficits.

A high fructose diet does not affect amphetamine self-administration or spatial water maze learning and memory in female rats

High energy diets can have a detrimental effect on brain plasticity. For example, a high fructose diet impairs spatial memory in male rats. The aim of the present study was to determine whether a high fructose diet impairs another form of learning and memory: drug reinforcement learning. Female Sprague-Dawley rats were fed a high fructose diet (60%) from weaning at postnatal day (PND) 21, then allowed to acquire lever-pressing maintained by intravenous (i.v.) amphetamine at PND 68, 109, or 165. Acquisition was tested on a fixed ratio one (FR1) schedule of reinforcement (0.025 mg/kg/infusion, 1h daily sessions, 10 sessions over 14 days), followed by testing for reinforcing efficacy on a progressive ratio (PR) schedule (0.025, 0.01, and 0.1mg/kg/infusion), 14 days of abstinence, and within-session extinction and reinstatement tests. Subsequently, water maze acquisition and retention were tested in these subjects as well as a separate cohort tested in the water maze only. The diet had no effect on acquisition, reinforcing efficacy, extinction, or reinstatement of amphetamine seeking. Nor did the diet alter any measures of spatial memory. The high fructose diet did decrease body mass and increase relative liver and spleen mass, but did not affect plasma triglyceride concentrations consistently. Together with prior research on males, these results suggest that the metabolism of fructose and the effects of a high fructose diet on learning and memory may be sex-dependent.

Excess intake of fat and sugar potentiates epinephrine-induced hyperglycemia in male rats

AIMSnOver the past five decades, per capita caloric intake has increased significantly, and diet- and stress-related diseases are more prevalent. The stress hormone epinephrine stimulates hepatic glucose release during a stress response. The present experiment tested the hypothesis that excess caloric intake alters this ability of epinephrine to increase blood glucose.nnnMETHODSnSprague-Dawley rats were fed a high-energy cafeteria-style diet (HED). Weight gain during the first 5 days on the diet was used to divide the rats into an HED-lean group and HED-obese group. After 9 weeks, the rats were injected with epinephrine, and blood glucose was measured.nnnRESULTSnHED-obese rats gained body and fat mass, and developed insulin resistance (IR) and hepatic steatosis. HED-lean and control rats did not differ. Epinephrine produced larger increases in blood glucose in the HED-obese rats than in the HED-lean and control rats. Removing the high-energy components of the diet for 4 weeks reversed the potentiated effects of epinephrine on glucose and corrected the IR but not the steatosis or obesity.nnnCONCLUSIONSnConsumption of a high-energy cafeteria diet potentiates epinephrine-induced hyperglycemia. This effect is associated with insulin resistance but not adiposity or steatosis and is reversed by 4 weeks of standard chow.

Social housing and social isolation: Impact on stress indices and energy balance in male and female Syrian hamsters (Mesocricetus auratus)

Although Syrian hamsters are thought to be naturally solitary, recent evidence from our laboratory demonstrates that hamsters may actually prefer social contact. Hamsters increase their preference for a location associated with an agonistic encounter regardless of whether they have won or lost. It has also been reported that social housing as well as exposure to intermittent social defeat or to a brief footshock stressor increase food intake and body mass in hamsters. By contrast, it has also been suggested that housing hamsters in social isolation causes anxiety-induced anorexia and reductions in body mass selectively in females. The purpose of this study was to determine the physiological consequences of housing hamsters in social isolation versus in social groups. Male and female hamsters were housed singly or in stable groups of 5 for 4weeks after which they were weighed and trunk blood was collected. In addition, fat pads and thymus and adrenal glands were extracted and weighed. Serum and fecal cortisol were measured using an enzyme-linked immunoassay. Housing condition had no effect on serum or fecal cortisol, but socially housed hamsters displayed modest thymus gland involution. Socially housed females weighed more than did any other group, and socially housed females and males had more fat than did socially isolated hamsters. No wounding or tissue damage occurred in grouped hamsters. Overall, these data suggest that Syrian hamsters tolerate both stable social housing and social isolation in the laboratory although social housing is associated with some alteration in stress-related and bioenergetic measures.

High energy diets prevent the enhancing effects of emotional arousal on memory.

Over the past five decades, per capita caloric intake has increased by approximately 28% in the United States. Excessive intake of calories from fats and sugars (high energy diets; HEDs) negatively impacts hippocampal-dependent memory. These deleterious effects of HEDs on hippocampal function involve HED-induced decreases in neuronal growth factors, neurogenesis, and synaptic plasticity. Given that HEDs also alter responses to emotional arousal, the present experiment determined whether the effects of HEDs on memory depend on the emotional arousal produced by the memory task during encoding. Rats were fed a high fat/sugar cafeteria-style diet for 4 weeks and then tested in a low or high emotional arousal version of a spatial object place recognition task. The results demonstrated that the HED prevented the memory-enhancing effects of emotional arousal. Thus, altered responses to emotional arousal likely contribute to HED-induced memory impairments, particularly in stressful memory tasks such as the spatial water maze.

Oxytocin- and arginine vasopressin-containing fibers in the cortex of humans, chimpanzees, and rhesus macaques.

Oxytocin (OT) and arginine‐vasopressin (AVP) are involved in the regulation of complex social behaviors across a wide range of taxa. Despite this, little is known about the neuroanatomy of the OT and AVP systems in most non‐human primates, and less in humans. The effects of OT and AVP on social behavior, including aggression, mating, and parental behavior, may be mediated primarily by the extensive connections of OT‐ and AVP‐producing neurons located in the hypothalamus with the basal forebrain and amygdala, as well as with the hypothalamus itself. However, OT and AVP also influence social cognition, including effects on social recognition, cooperation, communication, and in‐group altruism, which suggests connectivity with cortical structures. While OT and AVP V1a receptors have been demonstrated in the cortex of rodents and primates, and intranasal administration of OT and AVP has been shown to modulate cortical activity, there is to date little evidence that OT‐and AVP‐containing neurons project into the cortex. Here, we demonstrate the existence of OT‐ and AVP‐containing fibers in cortical regions relevant to social cognition using immunohistochemistry in humans, chimpanzees, and rhesus macaques. OT‐immunoreactive fibers were found in the straight gyrus of the orbitofrontal cortex as well as the anterior cingulate gyrus in human and chimpanzee brains, while no OT‐immunoreactive fibers were found in macaque cortex. AVP‐immunoreactive fibers were observed in the anterior cingulate gyrus in all species, as well as in the insular cortex in humans, and in a more restricted distribution in chimpanzees. This is the first report of OT and AVP fibers in the cortex in human and non‐human primates. Our findings provide a potential mechanism by which OT and AVP might exert effects on brain regions far from their production site in the hypothalamus, as well as potential species differences in the behavioral functions of these target regions.

Sucrose ingestion induces glutamate AMPA receptor phosphorylation in dorsal hippocampal neurons: Increased sucrose experience prevents this effect

HighlightsSucrose ingestion increased GluA1 pSer831 in dHC but not in vHC.Extensive sucrose experience prevented sucrose‐induced increases in dHC pSer831.Sucrose ingestion did not increase vHC pSer831.Sucrose ingestion did not affect GluA1 pSer845 in either dHC or vHC.Thus, sucrose ingestion activates a protein vital for synaptic plasticity in dHC during the postprandial period.These results are consistent with the hypothesis that dHC neurons form a memory of a meal. Abstract Evidence suggests that meal‐related memory influences later eating behavior. Memory can serve as a powerful mechanism for controlling eating behavior because it provides a record of recent intake that likely outlasts most physiological signals generated by ingestion. Dorsal (dHC) and ventral hippocampal (vHC) neurons are critical for memory, and we demonstrated previously that they limit energy intake during the postprandial period. If dHC or vHC neurons control intake through a process that requires memory, then ingestion should increase events necessary for synaptic plasticity in dHC and vHC during the postprandial period. To test this, we determined whether ingesting a sucrose solution induced posttranslational events critical for hippocampal synaptic plasticity: phosphorylation of AMPAR GluA1 subunits at 1) serine 831 (pSer831) and 2) serine 845 (pSer845). We also examined whether increasing the amount of previous experience with the sucrose solution, which would be expected to decrease the mnemonic demand involved in an ingestion bout, would also attenuate sucrose‐induced phosphorylation. Quantitative immunoblotting of dHC and vHC membrane fractions demonstrated that sucrose ingestion increased postprandial pSer831 in dHC but not vHC. Increased previous sucrose experience prevented sucrose‐induced dHC pSer831. Sucrose ingestion did not affect pSer845 in either dHC or vHC. Thus, the present findings show that ingestion activates a postranslational event necessary for synaptic plasticity in an experience‐dependent manner, which is consistent with the hypothesis that dHC neurons form a memory of a meal during the postprandial period.