Amer Kamal

Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

Cognitive performance and convulsion risk after experimentally-induced febrile-seizures in rat

Many reports indicated that small percentage of children with febrile seizures develop epilepsy and cognitive disorders later in adulthood. In addition, the neuronal network of the hippocampus was reported to be deranged in adult animals after being exposed to hyperthermia‐induced seizures in their neonatal life. The aims of this study were to investigate (1) latency and probability of seizures, (2) spatial learning and memory, in adult rats after neonatal hyperthermia‐induced febrile seizures (FS). Prolonged FS were elicited in 10‐day old, male Sprague Dawleys (n = 11/group) by exposure to heated air (48–52 °C) for 30 min; control rats were exposed to 30 °C air. After 1.5 months the animals cognitive performance was assessed by 5 day trial in the Morris water maze. In another experiment the latency and probability of seizures were measured in response to pentylenetetrazole (PTZ) injections (increased doses ranged from 7 to 140 mg/kg; i.p.). In water maze, both groups showed improvements in escape latency and distance swam to reach the platform; effects were significantly greater in control versus hyperthermia‐treated animals on days 3 and 4. Latency and probability of PTZ‐induced seizures were shorter and higher respectively, in hyperthermia‐treated animals compared to controls. We concluded that FS in neonatal rats leads to enhanced susceptibility for seizures, as well as cognitive deficits in adults.

Sex differences in learning and memory following short-term dietary restriction in the rat

Acute or prolonged dietary restriction has been shown to have significant effects on learning and memory, and also on the food seeking behaviour in animals.

Subacute exposure to 50-Hz electromagnetic fields affect prenatal and neonatal mice’s motor coordination

In this study, we investigate the possible effect of ELF-EMFs on motor performance in mice (prenatal and neonatal exposed mice). The mice performance is evaluated after 5 days of subacute exposure. Immature mice have been chosen for this study because the immature rodent brain still has the capacity to undergo proliferation, differentiation, and reorganization. Results from the rotarod experiments demonstrated a pronounced deficit in the learning abilities of the prenatal exposed groups, but no pronounced effect was observed for the neonatal exposed group.

Effects of exposure to 50 Hz electromagnetic fields on Morris water-maze performance of prenatal and neonatal mice

Abstract Extremely low-frequency magnetic fields (ELF-MF), such as those originating from residential and occupational power lines, household appliances and medical devices, have been reported repeatedly to produce a variety of biological effects, which may induce a number of changes in behavioral differences of different living species, like insects and rodents. The purpose of the present study is to investigate the possible effect of an extremely low-frequency magnetic field ELF-MF (50 Hz, 1 mT) on spatial learning and memory functions in mice (prenatal and neonatal exposed mice) following a continuous 7-day exposure, using Morris water-maze. Immature mice have been chosen for this study since; the immature rodent brain still has the capacity to undergo proliferation, differentiation and re-organization and more closely resembles the developing brain of a human child. Thus, the immature rodent brain may provide a sensitive and useful animal model to study the possible biological effects of ELF-MF. Our results provide convincing evidence that long time MF exposure to immature mice; causes appreciable long term deficit in learning abilities.

Autism-relevant social abnormalities in mice exposed perinatally to extremely low frequency electromagnetic fields.

The incidence of autism spectrum disorders (ASD) has been rising, but the causes of ASD remain largely unidentified. Collective data have implicated the increased human exposure to electromagnetic fields (EMF) in the increasing incidence of ASD. There are established biological effects of extremely low‐frequency (ELF) EMF, but the relation to ASD is not investigated enough. In this study we examined the effects of perinatal exposure to ELF EMF on some ASD‐relevant behavioral parameters in mice. The EMF was delivered via a Helmholtz coil pair. Male BALB/C mice were used and divided into exposed and control groups (n = 8 and n = 9, respectively). Tests were used to assess sociability, preference for social novelty, locomotion, anxiety, exploratory behavior, motor coordination, and olfaction. The examined mice were all males and exposed to EMF during the last week of gestation and for 7 days after delivery. The exposed mice demonstrated a lack of normal sociability and preference for social novelty while maintaining normal anxiety‐like behavior, locomotion, motor coordination, and olfaction. Exposed mice also demonstrated decreased exploratory activity. We concluded that these results are supportive of the hypothesis of a causal link between exposure to ELF–EMF and ASD; however, replications of the study with further tests are recommended.

Acute Administration of Caffeine: The Effect on Motor Coordination, Higher Brain Cognitive Functions, and the Social Behavior of BLC57 Mice

Excessive caffeine consumption causes adverse health effects. The effects of moderate and high doses of caffeine consumption on the motor coordination, cognitive brain functions, and the social behavior in mice were studied. Animals were divided into three groups: control group, moderate dose group (Ac MD), and high dose group (Ac HD). The animals were tested after 7 days of caffeine administration. A rotarod test for motor coordination showed that the mice of the moderate dose group could stay on the rotating rod longer before falling in comparison to the control group and the high dose group. A water maze test for learning and memory showed better performance of mice receiving the moderate dose of caffeine compared to the other groups. Animals that were administered moderate as well as high doses of caffeine showed no sociability and no preference for social novelty in the three-chamber test used to test social behavior. In an elevated plus maze test, control animals showed no anxiety-like behavior while mice from both of the groups administered with caffeine showed anxiety-like behaviors. Our data conclude that the effects of caffeine on higher brain functions depend on the administration dose. When caffeine was given in moderate doses, it resulted in enhancement of memory and motor coordination functions. However, high doses caused defects in memory and learning. The social behavior of the mice, as determined by the level of anxiety and sociability, was affected negatively by moderate as well as high dose caffeine administration.

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type 2 diabetes patients

The mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function and altered mtDNA-CN reflects the oxidant-induced cell damage. A previous study by our group demonstrated that a reduction in the renal mtDNA-CN is implicated in the pathogenesis of diabetic nephropathy (DN), a leading cause of end-stage renal disease in diabetic patients. In the present study, it was investigated whether the mtDNA-CN in the peripheral blood may be utilized as a biomarker for DN in type 2 diabetes (T2D) patients. The study included 50 non-diabetic and 100 diabetic subjects. The diabetic subjects were sub-divided based on their albumin-to-creatinine ratio (ACR) into T2D patients with normoalbuminuria (n=50), DN patients with microalbuminuria (n=29) and DN patients with macroalbuminuria (n=21). The mtDNA-CN was measured in the peripheral blood by real-time polymerase chain reaction analysis. Patients with DN had a lower mtDNA-CN than patients with T2D and healthy controls (P<0.05). A sub-group analysis with stratification by the ACR indicated that a decreased mtDNA-CN was associated with the severity and the presence of DN, as it was lower in DN patients with macroalbuminuria than in DN patients with microalbuminuria and T2D patients with normoalbuminuria (P<0.01). The area under the receiver operating characteristic curve (AUC) for mtDNA-CN was 0.916 (sensitivity, 86% and specificity, 74%) and 0.961 (sensitivity, 96% and specificity, 88%) for differentiating DN patients from T2D patients without DN and from healthy controls, respectively. Furthermore, the AUC of mtDNA-CN for differentiating DN patients with microalbuminuria from those with macroalbuminuria was 0.895 (sensitivity, 83% and specificity, 85%). Multivariate analysis revealed that the mtDNA-CN was significantly associated with the occurrence and progression of DN, even after adjustment for age, mean blood pressure, glycated haemoglobin A1c and total cholesterol (P<0.05). In patients with DN, a decreased mtDNA-CN was negatively correlated with albuminuria and conventional risk factors for DN, and was positively correlated with the estimated glomerular filtration rate. The present results therefore suggest the utilization of circulating mtDNA-CN as a novel biomarker for the early diagnosis of DN and indicate the significance of decreased mtDNA-CN as another independent risk factor for DN.

PT683. Effects of acute administration of moderate and high caffeine doses on the spatial memory and motor coordination in mice.

Objective: HYBID (Hyaluronan Binding Protein Involved in HA Depolymerization, KIAA1199) is a hyaluronan (HA) binding protein, which involves in depolymerization of HA. It is reported that HYBID mRNA is expressed in the lung, heart, skin and brain in murine and human. However, the role of HYBID in the brain remains unclear. In this study, we have made HYBID KO mice and evaluated its function in the central nervous system. Methods: To investigate the role of HYBID in brain, behavioral tests were performed by using HYBID KO mice. In situ hybridization was performed to investigate the localization of HYBID mRNA in mouse brain. Results: HYBID mRNA was expressed in the brain, especially hippocampus and cerebellum in wild-type mice, but not KO. HYBID KO mice showed decreased memory ability in a novel object recognition test. The expression of Hyal1 and Hyal2 mRNAs was not changed in the HYBID KO mouse brain. These results suggest that HYBID plays a key role in memory function in the brain. Conclusion: HYBID may be involved in brain function, such as memory and learning. Policy of Full Disclosure: None. PT681 The protective role of erythropoietin on the cognitive power deficit of the brain and histological changes in the hippocampus of diabetic mice. Amer Al Ansari, Ebrahim Rajab, Manal Othman, Muhammad AlNaisar, Ahmmed Almubarak Arabian Gulf University, College of Medicine and Medical Sciences,