Neuroscience
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Ghrelin is a peptide produced in the gut with a wide range of physiological functions. Recent studies have suggested it may have potential as a neuroprotective agent in models of Parkinson's disease, reducing the impact of toxic challenges on the survival of nigral dopaminergic neurons. The presence of the ghrelin receptor (GHSR1a) on the dopaminergic neurons of the substantia nigra raises the possibility that a potential application for this property of ghrelin may be as an adjunctive neuroprotective agent to enhance and support the survival and integration of dopaminergic cells transplanted into the striatum. ⋯ To determine a functional effect, five groups of female Sprague-Dawley rats received a unilateral 6-OHDA lesion to the medial forebrain bundle and four received an intrastriatal graft of e14 ventral mesencephalic cells. Grafted rats received saline; acyl-ghrelin (10 µg/kg); acyl-ghrelin (50 µg/kg) or the ghrelin agonist JMV-2894 (160 µg/kg) i.p. for 8 weeks. An effect of ghrelin at low dose on hippocampal neurogenesis indicated blood-brain barrier penetrance and attainment of biologically relevant levels but neither acyl-ghrelin nor JMV-2894 improved graft survival or efficacy.
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Alzheimer's disease is a chronic neurological ailment that seriously threatens human health and imposes a huge burden on families and the society at large. Emerging evidence suggests that neuroinflammation is an important pathological manifestation of neurodegenerative diseases, and currently considered a new research target. We previously found that artemisinin B from Artemisia annua Linn. has strong anti-inflammatory and immunological activities. ⋯ This study also showed that artemisinin B improved spatial memory in dementia mice in the water maze and step-through tests, and altered the pathological features and the levels of inflammatory cytokines in the hippocampus and the cortex. These results suggested that artemisinin B might inhibit neuroinflammation and exert neuroprotective effects on cognitive functions by modulating the TLR4-MyD88-NF-κB signaling pathway. This study provides direct evidence for the potential application of artemisinin B in the treatment of neuroinflammatory diseases.
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The Weak Central Coherence account of autism spectrum disorders posits that individuals with ASD utilize a detail-oriented information processing bias. While this local bias is helpful in visual search tasks, ASD individuals falter in social cognition tasks where coherence is advantageous. The present study examined the neural correlates of Weak Central Coherence in ASD during visual and social processing. ⋯ The TD group showed significantly increased areas of activity over the ASD group in the Shape task in regions associated with executive control, such as the medial prefrontal cortex and middle frontal gyrus, suggesting increased interference from the global/social information. During the Emotion condition, the ASD group showed decreased connectivity between frontal and posterior regions and between body perception and motor networks, suggesting a possible difference in mirroring. The findings suggest that social cognitive factors, not visual processing biases, underlie the observed behavioral differences.
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Cognitive impairment (CI), a debilitating and pervasive feature of multiple sclerosis (MS), is correlated with hippocampal atrophy. Findings from postmortem MS hippocampi indicate that expression of genes involved in both excitatory and inhibitory neurotransmission are altered in MS, and although deficits in excitatory neurotransmission have been reported in the MS model experimental autoimmune encephalomyelitis (EAE), the functional consequence of altered inhibitory neurotransmission remains poorly understood. In this study, we used electrophysiological and biochemical techniques to examine inhibitory neurotransmission in the CA1 region of the hippocampus in EAE. ⋯ Although plasma membrane expression of the GABA transporter GAT-3 was decreased in the EAE hippocampus, an increased surface expression of α5 subunit-containing GABAA receptors appears to be primarily responsible for the increase in tonic inhibition during EAE. Enhanced tonic inhibition during EAE was associated with decreased CA1 pyramidal cell excitability and inhibition of α5 subunit-containing GABAA receptors with the negative allosteric modulator L-655,708 enhanced pyramidal cell excitability in EAE mice. Together, our results suggest that altered GABAergic neurotransmission may underlie deficits in hippocampus-dependent cognitive function in EAE and MS.
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Stimulation of the mu-opioid receptor (MOR) on nociceptors with fentanyl can produce hyperalgesia (opioid-induced hyperalgesia, OIH) and hyperalgesic priming, a model of transition to chronic pain. We investigated if local and systemic administration of biased MOR agonists (PZM21 and TRV130 [oliceridine]), which preferentially activate G-protein over β-arrestin translocation, and have been reported to minimize some opioid side effects, also produces OIH and priming. Injected intradermally (100 ng), both biased agonists induced mechanical hyperalgesia and, when injected at the same site, 5 days later, prostaglandin E2 (PGE2) produced prolonged hyperalgesia (priming). ⋯ Hyperalgesia, analgesia and priming induced by systemic administration of PZM21 were also prevented by MOR AS-ODN. And, priming induced by systemic PZM21 was also not reversed by intradermal cordycepin or the combination of Src and MAPK inhibitors. Thus, maintenance of priming induced by biased MOR agonists, in the peripheral terminal of nociceptors, has a novel mechanism.