Neuroscience
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Because consumption of processed foods has increased in the last decades and so far its potential influence on emotionality and susceptibility to stress is unknown, we studied the influence of different fatty acids (FA) on behavioral and biochemical parameters after acute restrain stress (AS) exposure. Two sequential generations of female rats were supplemented with soybean oil (control group; C-SO), fish oil (FO) and hydrogenated vegetable fat (HVF) from pregnancy and during lactation. At 41days of age, half the animals of each supplemented group were exposed to AS and observed in open field and elevated plus maze task, followed by euthanasia for biochemical assessments. ⋯ Among groups exposed to AS, HVF increased reactive species generation in the brain, decreased cell viability in the cortex and striatum, and decreased catalase activity in the striatum and hippocampus. Taken together, our findings show that the type of FA provided during development and growth over two generations is able to modify the brain oxidative status, which was particularly adversely affected by trans fat. In addition, the harmful influence of chronic consumption of trans fats as observed in this study can enhance emotionality and anxiety parameters resulting from stressful situations of everyday life, which can trigger more severe neuropsychiatric conditions.
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In the present study we examined the effects of normal aging in the hippocampus and cerebellum, as well as behaviors associated with these substrates. A total of 67 CB6F1 hybrid mice were tested at one of five ages (4, 8, 12, 18 or 25 months) on the context pre-exposure facilitation effect (CPFE) modification of fear conditioning, rotorod, Barnes maze, acoustic startle, Morris water maze (MWM) and 500-ms trace eyeblink classical conditioning (EBCC). Behavioral tasks were chosen to increase the ability to detect age-related changes in learning, as trace EBCC is considered a more difficult paradigm (compared to delay EBCC) and the CPFE has been found to be more sensitive to hippocampus insults than standard contextual fear conditioning. ⋯ Although the CPFE task is considered more sensitive to hippocampus insult, no age-related impairment was found. Spatial memory retention was impaired in the Barnes maze at 25 months, but no significant deficits were seen in the MWM. These results support the finding of differential aging in the hippocampus and cerebellum.
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Increasing evidence has linked membrane cholesterol to amyloid precursor protein (APP) processing. β-Sitosterol (BS) is one of the most common forms of plant sterols, with the structure very similar to that of cholesterol. Using HT22 mouse hippocampal cells, this study investigated whether the substitution of membrane cholesterol with BS influences APP metabolism. ⋯ Additional experiments suggest that the effect of membrane BS on APP metabolism is associated with the migration of APP from lipid rafts toward non-raft regions. Given that dietary BS can enter the brain and accumulates in the plasma membrane of brain cells, these results suggest a potential use of BS in the prevention of Alzheimer's disease.
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Schizophrenia is a severe condition that has been associated with functional abnormalities in dopaminergic (DA) neurons of the ventral tegmental area (VTA). Neurokinin-3 receptors (NK3Rs) of the tachykinin family of neuropeptides modulate the activity of VTA DA neurons and might be involved in DA abnormalities relevant to schizophrenia. Recent work from our lab showed that systemic injection of the dopamine D1/D2 receptor agonist apomorphine in rats, which mimics schizophrenia-like behaviors in humans, also evoked a redistribution of NK3Rs in DA neurons of the rat VTA. ⋯ In non-TH, presumably GABAergic neurons of the VTA, the NK3R densities in somata and dendrites were not significantly changed by apomorphine with or without SB222200. The results suggest that the NK3R antagonist SB222200 is effective against the apomorphine-evoked NK3R internalization in VTA DA dendrites, but does not prevent nuclear NK3R trafficking in VTA DA neurons. These results might have important implications in targeting NK3R antagonists in basic or clinical studies.
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Various protein motifs play a key role in regulating protein biogenesis and trafficking. Here, we discovered that three distinct motifs regulate the trafficking of acid-sensing ion channel 1a (ASIC1a), the primary neuronal proton receptor which plays critical roles in neurological diseases including stroke, multiple sclerosis and seizures. Mutating the PDZ binding motif of ASIC1a increased its surface expression and current density. ⋯ These changes were likely due to a change in ASIC1a biogenesis; mutating either the RRGK or KEAKR motif reduced N-glycosylation of ASIC1a while mutating the PDZ binding motif had the opposite effect. Our results demonstrate that these C-terminal motifs are important for ASIC1a trafficking and channel function. In addition, in contrast to multiple previous studies, which all show that K/R containing motifs lead to endoplasmic reticulum (ER) retention, our findings indicate that these motifs can also be required for efficient trafficking.