Most primary olfactory neurons have individually neutral effects on behavior.

Animals use olfactory receptors to navigate mates, food, and danger. However, for complex olfactory systems, it is unknown what proportion of primary olfactory sensory neurons can individually drive avoidance or attraction. Similarly, the rules that govern behavioral responses to receptor combinations are unclear. We used optogenetic analysis in Drosophila to map the behavior elicited by olfactory-receptor neuron (ORN) classes: just one-fifth of ORN-types drove either avoidance or attraction. Although wind and hunger are closely linked to olfaction, neither had much effect on single-class responses. Several pooling rules have been invoked to explain how ORN types combine their behavioral influences; we activated two-way combinations and compared patterns of single- and double-ORN responses: these comparisons were inconsistent with simple pooling. We infer that the majority of primary olfactory sensory neurons have neutral behavioral effects individually, but participate in broad, odor-elicited ensembles with potent behavioral effects arising from complex interactions.

The investigation of protective effects of glucagon-like peptide-1 (GLP-1) analogue exenatide against glucose and fructose-induced neurotoxicity.

Diabetes mellitus (DM) is one of the most common metabolic disorders characterized by hyperglycemia due to insufficiency of insulin and/or insulin resistance. Clinical studies have revealed a higher risk of neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease in diabetic patients. Recently, glucagon-like peptide-1 (GLP-1) is an attractive potential treatment modality for various neurodegenerative diseases. In our study, we aimed to investigate whether exenatide, a GLP-1 analogue, has neuroprotective effects against glucose and fructose-induced toxicity in human SH-SY5Y neuroblastoma cell line. Neurotoxicity was induced by incubating SH-SY5Y cells with different doses (25-100 mM) of glucose and fructose for 24, 48 and 72 hours. Following determination of the significant toxic doses of glucose and fructose, the cells were treated with various doses of exenatide (10-250 nM) in the presence or absence of glucose and fructose. Neurotoxicity was evaluated by MTT assay and Hoechst 33258 staining. Caspase-3 activity and the levels of advanced glycation end products (AGEs) were determined in the cytosolic fractions of treated cells. Our results demonstrated that both glucose and fructose treatments decreased cell viability in neuronal cells dose and time-dependently. Glucose and fructose-treated groups showed increased numbers of apoptotic cells, caspase-3 activity and AGEs levels. Treatment of the cells with exenatide significantly prevented cell death. The most prominent effect was observed at 100 nM exenatide-treated cultures. Our results suggest that high doses of glucose and fructose may lead to neurotoxicity, and exenatide may have protective effects against neuronal damage through its anti-apoptotic feature.

Neurobehavioral effects of long-term maternal fructose intake in rat offspring.

BACKGROUND: Previous studies have indicated an association between maternal metabolic conditions and general developmental disturbances of the offspring. OBJECTIVE: We aimed to investigate the influence of long-term maternal fructose intake during gestation and lactation on neurobehavioral development of rat offspring. METHODS: Twelve female Sprague Dawley rats were received either 30% fructose enriched water (n = 6) or regular tap water (control, n = 6) for 12 weeks. Then, control and fructose-received females were caged with a fertile male, and received 30% fructose and regular chow throughout pregnancy, delivery and until offspring's weaning. On P21, forty littermates (10 male control, 10 female control, 10 male fructose and 10 female fructose) were separated and housed with ad libitum access to standard food and tap water. Following behavioral evaluations at P50, brain levels of TNF-α, neuregulin 1 (NRG1), glutamic acid decarboxylase 67 (GAD67), nerve growth factor (NGF), insulin-like growth factor 1 (IGF-1), and 5-hydroxyindoleacetic acid (5-HIAA) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed. RESULTS: Analysis of the behavioral tests (three-chamber social test, open field test, passive avoidance learning test and stereotypy test) revealed significant differences among the groups. Histologically, hippocampal CA1 and CA3 regions displayed significant alterations such as gliosis and neuronal cell death in fructose-exposed groups compare to controls. Biochemical measurements of the brain levels of TNF-α and neurodevelopmental markers showed significant differences between controls and fructose-exposed groups. CONCLUSION: These results suggest a possible link between the chronic maternal metabolic stress, such as long-term fructose intake, and neurodevelopmental disturbances in the offspring.

Evaluation of long-term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study.

The aim of the present study was to compare the effects of artificial sweeteners (aspartame, saccharin, and sucralose) on rat brain. Twenty-four adult male Sprague-Dawley rats were included in the study. The control group (n = 6) received regular tap water, whereas other groups received aspartame (3 mg/kg/day, n = 6,) or saccharin (3 mg/kg/day, n = 6) or sucralose (1.5 mg/kg/day, n = 6) in the drinking water. Following 6 weeks, the passive avoidance learning (PAL) test was performed to evaluate the neurobehavioral effects of sweeteners. The brains were assessed for lipid peroxides, neuron count, and Glial fibrillary acidic protein (GFAP) immunohistochemistry. Our results demonstrated that chronic intake of sweeteners significantly impaired PAL performance in all groups. Hippocampal CA1-CA3 areas revealed significantly lower neuronal count in aspartame and increased GFAP expression in all groups. Brain lipid peroxides were significantly higher in all groups. Our findings suggest that long-term consumption of artificial sweeteners may have harmful effects on cognition and hippocampal integrity in rats.

Protective effect of edaravone against manganese-induced toxicity in cultured rat astrocytes.

Manganese (Mn), a trace metal, is essential for maintaining the normal regulation of many biochemical and cellular processes. However, accumulation of Mn due to excessive environmental exposure leads to neurological impairment, referred to as manganism. Edaravone (EDA) is a potent free radical scavenger that has been clinically shown to reduce the neuronal injury after cerebral ischemia. In the present study, we aimed to examine the protective effects of EDA against Mn toxicity in astrocyte cultures. Astrocyte cultures were prepared from cerebral cortices of newborn Sprague-Dawley rats. The experiments were performed between 16 and 18 days of cultures. Astrocytes were treated in DMEM medium containing Mn (1-1000µM) for 24h to test Mn toxicity. In order to assess the effect of EDA, cells were pre-treated with different doses of EDA (10, 100 and 1000µM) 6h before Mn treatment. Cell viability (MTT), apoptotic cell death (Hoechst test) and lipid peroxide levels were evaluated in cultures. Our results showed that Mn significantly and dose-dependently reduced cell viability in astrocyte cultures. The apoptotic cell death and lipid peroxides were significantly higher in Mn treated cultures. Treatment of astrocytes with EDA successfully suppressed oxidative stress and cell death due to Mn exposure. The findings of the present study suggest that Mn cytotoxicity is mainly associated with ROS generation and apoptotic cell death. Besides, EDA may have beneficial effects against Mn toxicity. However, further studies are needed to elucidate the molecular mechanisms underlying protective effect of EDA.