Brain research bulletin
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Brain research bulletin · Sep 2020
Modulatory role of hippocampal dopamine receptors in antinociceptive responses induced by chemical stimulation of the lateral hypothalamus in an animal model of persistent inflammatory pain.
The lateral hypothalamus (LH) plays a complicated role in the modulation of inflammatory pain. There are a number of connections between the LH and the hippocampus. This study evaluated the pain modulatory role of intra-CA1 dopamine receptors in LH chemical stimulation-induced antinociception in the formalin test (persistent inflammatory pain model). ⋯ The inhibitory effects of the D1 or D2-like dopamine receptor antagonist on LH chemical stimulation-induced analgesia was nearly the same in the both phases of formalin-induced pain-related behaviors. The findings show that the LH-CA1 pathway contributes to the modulation of formalin-induced pain. Moreover, the results indicate that D1- and D2-like dopamine receptors in the CA1 participate in the LH chemical stimulation-induced antinociception.
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Brain research bulletin · Nov 2019
Fingolimod (FTY720) improves the functional recovery and myelin preservation of the optic pathway in focal demyelination model of rat optic chiasm.
It has been shown that fingolimod (FTY720) possesses beneficial effects on remyelination in the central nervous system (CNS). In this study, the effects of FTY720 and sodium valproate (VPA) as histone deacetylase inhibitor (HDAC) on the conductivity of visual signals, extent of demyelination area, glial activation, and expression levels of HDAC1and S1PR1 have been evaluated in the optic chiasm of lysolecithin (LPC)-induced demyelination model. In order to produce this demyelination model, LPC (1%, 2 μL) was injected into the rat optic chiasm. ⋯ Additionally, the expression levels of HDAC1 and S1PR1 were significantly reduced in animals treated with FTY720. In contrast to FTY720 treated animals, administration of VPA could not significantly improve the functional recovery of optic pathway following LPC injection. Cumulatively, the results of the present study demonstrate that FTY720 application improves the functional recovery of the optic pathway by reducing demyelination levels, amelioration of glial activation, and down-regulating of S1PR1 and HDAC1.
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Brain research bulletin · Oct 2019
The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T+ Itpr3tf/J mouse model of autism.
Autism is a complex neurodevelopmental disorder with a high incidence rate. It is characterized by deficits in communication, a lack of social skills, cognitive inflexibility, and stereotypical behaviors. Autism has been gradually increasing in children over the past several years, without the existence of an effective treatment. ⋯ The objective of the present study was to further explore the role of S3I-201 in BTBR mice, and this was performed by investigating the effects of S3I-201 treatment on lymphocyte activation markers (CD4+CD25+ and CD4+CD69+), chemokine receptors (CD4+CCR6+, CD4+CCR7+, CD4+CXCR4+, and CD4+CXCR5+), and proinflammatory cytokines (CD4+IL-6+ and CD4+TNF-α+) in the spleen cells of BTBR and C57BL/6 (C57) mice. The mRNA and protein expression levels of CD69, CCR6, CCR7, CXCR4, CXCR5, IL-1β, IL-6, and TNF-α were examined in the brain tissues, and in BTBR mice, a significant decrease in CD25, CD69, CCR6, CCR7, CXCR4, CXCR5, IL-6, and TNF-α producing CD4+ T cells was observed. The present findings suggest that treatment with S3I-201 may be a therapeutic approach to improve immune abnormalities in a subgroup of autistic subjects.
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Purinergic signaling has recently been suggested to constitute the cellular mechanism underlying acupuncture-induced analgesia (AA). By extending the original hypothesis on endogenous opioids being released during AA, Geoffrey Burnstock and Maiken Nedergaard supplied evidence for the involvement of purinoceptors (P2 and P1/A1 receptors) in the beneficial effects of AA. ⋯ Because clinical studies on AA yielded sometimes heterogeneous results, it is of eminent importance to relay on experiments carried out on laboratory animals, by evaluating the data with stringent statistical methods including comparison with a sufficient number of control groups. In this review, we summarize the state of the art situation with respect to the participation of P2 receptors in AA and try to forecast how the field is likely to move forward in the future.
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Brain research bulletin · Aug 2019
ReviewParkinson's disease and light: The bright and the Dark sides.
Light exerts a major influence on human behaviour and health, mainly owing to the importance of sight in our lives, but also due to its entrainment of daily rhythms via the suprachiasmatic nucleus, the master pacemaker. Light may also be a useful clinical medium, as in lumino-therapy for the improvement of depressed mood. Further, as discussed herein, local application of near infrared light to the substantia nigra exerts neuroprotective properties in models of Parkinson's disease. ⋯ In general, as regards the growing problem to human health - and the natural world - of excess exposure to artificial light: both urban glow and ubiquitous screens. Moreover, over-exposure to light, in particular fluorescent light, disrupts circadian rhythms and sleep, and may damage dopaminergic neurons. Is it, then, a neglected risk factor for Parkinson's disease? The present article discusses epidemiological and experimental evidence supporting beneficial and potentially deleterious impact of light on dopaminergic neurons and highlights the mechanisms whereby light might influence neuronal tissue.