Neuroscience
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Interleukin-1β (IL-1β) and prostaglandin (PG) D2 are endogenous sleep-promoting substances. Since it was reported that a highly selective cyclooxygenase-2 (COX-2) inhibitor, NS398, completely inhibited IL-1β-induced sleep in rats, IL-1β-induced sleep had been believed to be mediated by prostanoids, most probably PGD2. ⋯ Meanwhile, IL-1β at doses of 1.7 and 5μg/kg also significantly increased NREM sleep for 6h after intraperitoneal injection at 20:00 (light-off time) by 76.8% and 121.1%, respectively, in wild-type (WT) mice, by 67.7% and 147.3%, respectively, in WT mice pretreated with NS398 (5mg/kg) and by 108.9% and 121.6%, respectively, in PGD2 receptor (DP1R) knockout mice. These results indicate that IL-1β-induced NREM sleep is independent of the PGD2/DP1R system and other COX-2-derived prostaglandins in rats and mice.
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Parkinson's disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum. Recent studies have demonstrated that the nuclear receptor-related 1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2). ⋯ To evaluate the effects of MABH on Nurr1 expression, we measured the protein levels of Nurr1 and its regulating factors using Western blot analysis in PC12 cells. MABH treatment induced the phosphorylation of extracellular signal-regulated kinase protein via increasing the protein expression levels of Nurr1 and ultimately the levels of TH, VMAT2, and DAT. These results indicate that MABH has protective effects on dopaminergic neurons in a mouse model of PD by regulating Nurr1.
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Cannabinoid type-1 (CB1) and transient receptor potential vanilloid type-1 (TRPV1) receptors may have opposite roles in modulating neural activity and, consequently, in regulating the stress response. These receptors are widely expressed in several brain structures, including the ventral medial prefrontal cortex (vmPFC). The functional consequences of the interaction between CB1 and TRPV1, however, have scarcely been explored. ⋯ Furthermore, the co-administration of URB597 and SB366791 in sub-effective doses induced an antidepressant-like effect in the FST. Additionally, the antidepressant-like effect of AA-5HT was prevented by the CB1 antagonist. Together, these results suggest that both, CB1 and TRPV1 receptors located in the vmPFC are involved in the behavioral responses to stress, although in opposite ways.
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The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A2 (iPLA2) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, maprotiline. ⋯ These changes were not observed in maprotiline-treated mice that received iPLA2 antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA2 and its enzymatic products in the antinociceptive effect of maprotiline.
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The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat's life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels. ⋯ In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain. Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals.