Changes associated with cognitive function in the high-fat high-carbohydrate diet-induced prediabetes animal model and effect of exercise remain unclear. Rats were randomly assigned to the following groups (n = 6): non-diabetic (ND), prediabetic (PD), intermittent exercising PD (PD + IE) and regular exercising PD (PD + RE). After exercise cessation, oral glucose tolerance (OGT), Novel Object Recognition Test (NORT) and Morris-Water Maze (MWM) tests were performed to assess cognitive function. After sacrifice, malonaldehyde, glutathione peroxidase, interleukin-1β and dopamine concentration in the prefrontal cortex (PFC) and hippocampus were measured. Impaired OGT response in PD animals was accompanied by poor performance on behavioural tasks. This was associated with increased oxidative stress markers and impaired dopamine neurotransmission as evidence by elevated dopamine concentration in the PFC and hippocampal tissue. Improved OGT response by exercise was coupled with improved performance on behavioural tasks, oxidative stress markers and increased interleukin-1β concentration. In regular exercise, this was further coupled with improved dopamine neurotransmission. Cognitive function was affected during prediabetes in animals. This was partly due to oxidative stress and impaired dopamine neurotransmission. Both intermittent and regular exercise improved cognitive function. This was partly mediated by improved glucose tolerance and oxidative stress as well as a subclinical increase in interleukin-1β concentration. In regular exercise, this was further mediated by improved dopamine neurotransmission.

Background: An animal model of prediabetes that has been developed in our laboratory using a high fat high carbohydrate diet and lack of physical activity displays risk factors for cardiovascular complications. The effect of exercise against these risk factors in this animal model remains unknown. Therefore, we evaluated the effect of intermittent and regular exercise treatment on the risk factors for cardiovascular complications in this animal model of prediabetes.Methods: Following prediabetes induction, animals were randomly assigned to the following groups (n = 6): non-diabetic, prediabetic, intermittently exercising prediabetic and regularly exercising prediabetic. Exercise exposure was 7 weeks long. Body weight changes, caloric intake, blood glucose, total cholesterol, and triglyceride concentration was measured after 20 and 29 weeks while blood pressure was only measured after 29 weeks. Plasma endothelial nitric oxide synthase, malonaldehyde, glutathione peroxidase, tumour necrosis factor-alpha and C-reactive protein concentration from the heart were measured 2 weeks post-exercise termination (week 30).Results: We found increased body weight, caloric intake and mean arterial pressure in the prediabetic group by comparison to the non-prediabetic group. The same trend was observed in blood glucose and triglyceride concentrations. However, all of these parameters were reduced in the intermittently exercising prediabetic and regularly exercising prediabetic groups. This reduction was further accompanied by a decrease in the endothelial nitric oxide synthase, tumour necrosis factor-alpha and C-reactive protein concentration with improved oxidative stress biomarkers.Conclusions: The progression of pre-diabetes to diabetes is slowed or possibly stopped by exercise (regular or intermittent). Additionally, biomarker profiles indicative of cardiovascular disease in pre-diabetics are improved by exercise.

The pathophysiology behind negative and cognitive symptoms of schizophrenia is not well understood, thus limiting the effectiveness of treatment on these symptoms. Developing reliable animal model of schizophrenia is vital to advance our understanding on the neurobiological basis of the disorder. Double hit is used to refer to the use of two schizophrenia inducing interventions viz ketamine exposure and social isolation. In this study we aim to investigate the robustness of double hit model of schizophrenia in inducing negative and cognitive symptoms of schizophrenia. On postnatal day (PND) 23, thirty-two male Sprague Dawley rats were randomly grouped into four equal groups as follows: group housed + saline (GH), group housed + ketamine (GHK), isolated + saline (SI), and isolated + ketamine (SIK). A single ketamine dose (16 mg/kg) was administered 3 times a week for four weeks. Isolated animals were housed singly throughout the study. The following behavioural tests were carried out: elevated plus maze, three chamber social interaction, resident intruder tests, and novel object recognition (NOR). The SIK group exhibited high anxiety levels, with increased ACTH, corticosterone and norepinephrine concentration when compared to the other groups. The SIK animals also presented with reduced social interaction and decreased oxytocin concentration. SIK rats were more aggressive towards a juvenile intruder but had low testosterone concentration. The SIK group or double hit model showed impaired visual learning and memory and increased expression of proinflammatory cytokines. This suggest that the double hit model is more robust in inducing negative and cognitive symptoms of schizophrenia than each treatment alone.

There is a dual rise in social disconnection and sleep deprivation among adolescents in modern society. This is associated with an alarming increase in anxiety-related conditions and repeated risky behaviours in adolescents. Therefore, we investigated anxiety-like behaviours and aversive memory performance in adolescent animals following combined isolation and sleep disturbance.Animals were assigned to the following groups (n=7/group): control, group-housed sleep-disturbed, individually housed non-sleep-disturbed, and individually housed sleep-deprived. On day 18, the animals performed the plus-maze discriminative avoidance task to assess anxiety-like behaviours and aversive memory performance. We measured plasma adrenocorticotropin (ACTH), plasma corticosterone, amygdala arginine vasopressin (AVP), and prefrontal cortex interleukin-6 (IL-6) concentrations.Combined prolonged isolation and recurrent sleep disturbance worsened anxiety-like behaviour in adolescent animals, as evidenced by the least time spent in the open arms and the most time spent in the closed arms. This was accompanied by heightened HPA-axis activity, as indicated by higher plasma ACTH and amygdala AVP concentrations. This was associated with poor aversive memory performance, as evidenced by the most time spent in the previously aversive closed arm in these animals. Corticosterone and IL-6 concentrations did not change.Altogether, our findings suggest that an anxiety phenotype may lead to impaired aversive memory when it is accompanied by increased HPA-axis activity in adolescents, as observed in the animals following the combination of prolonged isolation and recurrent sleep disturbance. This re-entry into previously aversive closed arms by adolescent animals may result in repeated exposure to dangerous, painful or harmful experiences in human adolescents.