l organization of WM structural networks. This suggested that a compensatory mechanism plays a key role in global topology formation in both FTumor and TTumor patients, and as such, development of a structural connectome for patients with brain tumors would be an invaluable medical resource and allow clinicians to make comprehensive preoperative planning. Copyright © 2020 Liu, Yang, Hu, Xiao, Rao, Li, Liu, Zou, Chen and Liu.Addicted individuals are highly susceptible to relapse when exposed to drug-associated conditioned stimuli (CSs; "drug cues") even after extensive periods of abstinence. Until recently, these maladaptive emotional drug memories were believed to be permanent and resistant to change. The rediscovery of the phenomenon of memory reconsolidation-by which retrieval of the memory can, under certain conditions, destabilize the previously stable memory before it restabilizes in its new, updated form-has led to the hypothesis that it may be possible to disrupt the strong maladaptive drug-memories that trigger a relapse. Furthermore, recent work has suggested that extinction training "within the reconsolidation window" may lead to a long-term reduction in relapse without the requirement for pharmacological amnestic agents. However, this so-called "retrieval-extinction" effect has been inconsistently observed in the literature, leading some to speculate that rather than reflecting memory updating, it may be the product of facilitation of extinction. In this mini review article, we will focus on factors that might be responsible for the retrieval-extinction effects on preventing drug-seeking relapse and how inter-individual differences may influence this therapeutically promising effect. A better understanding of the psychological and neurobiological mechanisms underpinning the "retrieval-extinction" paradigm, and individual differences in boundary conditions, should provide insights with the potential to optimize the translation of "retrieval-extinction" to clinical populations. Copyright © 2020 Kuijer, Ferragud and Milton.Morphine is a potent analgesic opiate commonly used in treating pain, and it is also a substance of abuse and highly addictive. Hence, it is vital to discover the action sites of morphine in the brain to increase its efficacy of treatment. In the present study, we aimed at identifying comprehensive neuroanatomical locations that are sensitive to morphine in the adult zebrafish (Danio rerio). https://www.selleckchem.com/products/gf109203x.html We performed in situ hybridization to localize the mu opioid receptor (oprm1) gene and to map the morphine sensitive brain areas using neuronal PAS domain-containing protein 4a (npas4a), an early gene marker. Real-time PCR was used to detect changes in mRNA levels of oprm1 and npas4a in control and acute morphine treated fish (2 mg/L; 20 min). Intense positive oprm1 signals were seen in the telencephalon, preoptic area, habenula, hypothalamic area and periventricular gray zone of the optic tectum. Acute morphine exposure significantly increased oprm1 and npas4a mRNA levels in the medial zone of dorsal telencephalon (Dm), ventral region of the ventral telencephalon (Vv), preoptic area, and in the hypothalamus but a decrease in oprm1 and npas4a signals in the dorsal habenula. This study provides a detailed map of oprm1 localization in the brain, which includes previously unreported oprm1 in the habenula of teleost. Presence of oprm1 in multiple brain sites implies multiple action targets of morphine and potential brain functions which could include reward, cognitive and negative emotions. Copyright © 2020 Sivalingam, Ogawa and Parhar.Hair cells are sensitive to many insults including environmental toxins such as heavy metals. We show here that cadmium can consistently kill hair cells of the zebrafish lateral line. Disrupting hair cell mechanotransduction genetically or pharmacologically significantly reduces the amount of hair cell death seen in response to cadmium, suggesting a role for mechanotransduction in this cell death process, possibly as a means for cadmium uptake into the cells. Likewise, when looking at multiple cilia-associated gene mutants that have previously been shown to be resistant to aminoglycoside-induced hair cell death, resistance to cadmium-induced hair cell death is only seen in those with mechanotransduction defects. In contrast to what was seen with mechanotransduction, significant protection was not consistently seen from other ions previously shown to compete for cadmium uptake into cells or tissue including zinc and copper. These results show that functional mechanotransduction activity is playing a significant role in cadmium-induced hair cell death. Copyright © 2020 Schmid, Alampi, Briggs, Tarcza and Stawicki.Central nervous system (CNS) injury results in chronic scar formation that interferes with function and inhibits repair. Extracellular matrix (ECM) is prominent in the scar and potently regulates cell behavior. However, comprehensive information about the ECM proteome is largely lacking, and region- as well as injury-specific differences are often not taken into account. These aspects are the focus of our perspective on injury and scar formation. To highlight the importance of such comprehensive proteome analysis we include data obtained with novel analysis tools of the ECM composition in the scar and show the contribution of monocytes to the ECM composition after traumatic brain injury (TBI). Monocyte invasion was reduced using the CCR2-/- mouse line and step-wise de-cellularization and proteomics allowed determining monocyte-dependent ECM composition and architecture of the glial scar. We find significant reduction in the ECM proteins Tgm1, Itih (1,2, and 3), and Ftl in the absence of monocyte invasion. We also describe the scar ECM comprising zones with distinctive composition and show a subacute signature upon comparison to proteome obtained at earlier times after TBI. These results are discussed in light of injury-, region- and time-specific regulation of scar formation highlighting the urgent need to differentiate injury conditions and CNS-regions using comprehensive ECM analysis. Copyright © 2020 Kjell and Götz.
l organization of WM structural networks. This suggested that a compensatory mechanism plays a key role in global topology formation in both FTumor and TTumor patients, and as such, development of a structural connectome for patients with brain tumors would be an invaluable medical resource and allow clinicians to make comprehensive preoperative planning. Copyright © 2020 Liu, Yang, Hu, Xiao, Rao, Li, Liu, Zou, Chen and Liu.Addicted individuals are highly susceptible to relapse when exposed to drug-associated conditioned stimuli (CSs; "drug cues") even after extensive periods of abstinence. Until recently, these maladaptive emotional drug memories were believed to be permanent and resistant to change. The rediscovery of the phenomenon of memory reconsolidation-by which retrieval of the memory can, under certain conditions, destabilize the previously stable memory before it restabilizes in its new, updated form-has led to the hypothesis that it may be possible to disrupt the strong maladaptive drug-memories that trigger a relapse. Furthermore, recent work has suggested that extinction training "within the reconsolidation window" may lead to a long-term reduction in relapse without the requirement for pharmacological amnestic agents. However, this so-called "retrieval-extinction" effect has been inconsistently observed in the literature, leading some to speculate that rather than reflecting memory updating, it may be the product of facilitation of extinction. In this mini review article, we will focus on factors that might be responsible for the retrieval-extinction effects on preventing drug-seeking relapse and how inter-individual differences may influence this therapeutically promising effect. A better understanding of the psychological and neurobiological mechanisms underpinning the "retrieval-extinction" paradigm, and individual differences in boundary conditions, should provide insights with the potential to optimize the translation of "retrieval-extinction" to clinical populations. Copyright © 2020 Kuijer, Ferragud and Milton.Morphine is a potent analgesic opiate commonly used in treating pain, and it is also a substance of abuse and highly addictive. Hence, it is vital to discover the action sites of morphine in the brain to increase its efficacy of treatment. In the present study, we aimed at identifying comprehensive neuroanatomical locations that are sensitive to morphine in the adult zebrafish (Danio rerio). https://www.selleckchem.com/products/gf109203x.html We performed in situ hybridization to localize the mu opioid receptor (oprm1) gene and to map the morphine sensitive brain areas using neuronal PAS domain-containing protein 4a (npas4a), an early gene marker. Real-time PCR was used to detect changes in mRNA levels of oprm1 and npas4a in control and acute morphine treated fish (2 mg/L; 20 min). Intense positive oprm1 signals were seen in the telencephalon, preoptic area, habenula, hypothalamic area and periventricular gray zone of the optic tectum. Acute morphine exposure significantly increased oprm1 and npas4a mRNA levels in the medial zone of dorsal telencephalon (Dm), ventral region of the ventral telencephalon (Vv), preoptic area, and in the hypothalamus but a decrease in oprm1 and npas4a signals in the dorsal habenula. This study provides a detailed map of oprm1 localization in the brain, which includes previously unreported oprm1 in the habenula of teleost. Presence of oprm1 in multiple brain sites implies multiple action targets of morphine and potential brain functions which could include reward, cognitive and negative emotions. Copyright © 2020 Sivalingam, Ogawa and Parhar.Hair cells are sensitive to many insults including environmental toxins such as heavy metals. We show here that cadmium can consistently kill hair cells of the zebrafish lateral line. Disrupting hair cell mechanotransduction genetically or pharmacologically significantly reduces the amount of hair cell death seen in response to cadmium, suggesting a role for mechanotransduction in this cell death process, possibly as a means for cadmium uptake into the cells. Likewise, when looking at multiple cilia-associated gene mutants that have previously been shown to be resistant to aminoglycoside-induced hair cell death, resistance to cadmium-induced hair cell death is only seen in those with mechanotransduction defects. In contrast to what was seen with mechanotransduction, significant protection was not consistently seen from other ions previously shown to compete for cadmium uptake into cells or tissue including zinc and copper. These results show that functional mechanotransduction activity is playing a significant role in cadmium-induced hair cell death. Copyright © 2020 Schmid, Alampi, Briggs, Tarcza and Stawicki.Central nervous system (CNS) injury results in chronic scar formation that interferes with function and inhibits repair. Extracellular matrix (ECM) is prominent in the scar and potently regulates cell behavior. However, comprehensive information about the ECM proteome is largely lacking, and region- as well as injury-specific differences are often not taken into account. These aspects are the focus of our perspective on injury and scar formation. To highlight the importance of such comprehensive proteome analysis we include data obtained with novel analysis tools of the ECM composition in the scar and show the contribution of monocytes to the ECM composition after traumatic brain injury (TBI). Monocyte invasion was reduced using the CCR2-/- mouse line and step-wise de-cellularization and proteomics allowed determining monocyte-dependent ECM composition and architecture of the glial scar. We find significant reduction in the ECM proteins Tgm1, Itih (1,2, and 3), and Ftl in the absence of monocyte invasion. We also describe the scar ECM comprising zones with distinctive composition and show a subacute signature upon comparison to proteome obtained at earlier times after TBI. These results are discussed in light of injury-, region- and time-specific regulation of scar formation highlighting the urgent need to differentiate injury conditions and CNS-regions using comprehensive ECM analysis. Copyright © 2020 Kjell and Götz.
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