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Mashup Score: 5Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane - 1 day(s) ago
Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed treatment for individuals experiencing major depressive disorder. The therapeutic mechanisms that take place before, during, or after SSRIs bind the serotonin transporter (SERT) are poorly understood, partially because no studies exist on the cellular and subcellular pharmacokinetic properties of SSRIs in living cells. We studied escitalopram and fluoxetine using new intensity-based, drug-sensing fluorescent reporters targeted to the plasma membrane, cytoplasm, or endoplasmic reticulum (ER) of cultured neurons and mammalian cell lines. We also used chemical detection of drug within cells and phospholipid membranes. The drugs attain equilibrium in neuronal cytoplasm and ER at approximately the same concentration as the externally applied solution, with time constants of a few s (escitalopram) or 200–300 s (fluoxetine). Simultaneously, the drugs accumulate within lipid membranes by ≥18-fold (escitalopram) or 180-fold
Source: www.jneurosci.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 22The Intellectual Disability Risk Gene Kdm5b Regulates Long-Term Memory Consolidation in the Hippocampus - 3 day(s) ago
The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders, and heterozygous, protein-truncating variants in KDM5B are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a Kdm5b Δ ARID allele that lacks demethylase activity. Kdm5b Δ ARID/ Δ ARID mice exhibited hyperactivity and long-term memory deficits in hippocampus-dependent learning tasks. The expression of immediate early, activity-dependent genes was downregulated in these mice and hyperactivated upon a learning stimulus compared with wild-type (WT) mice. A number of other learning-associated genes were also significantly dysregulated in the Kdm5b Δ ARID/ Δ ARID hippocampus. Next, we
Source: www.jneurosci.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 2This Week in The Journal - 3 day(s) ago
Siyu Chen, Rachel M. Rahn, Annie R. Bice, Seana H. Bice, Jonah A. Padawar-Curry et al. (see article e1019232024) During the visual critical period, visual circuits are more plastic and adapt their connections in response to sensory stimulation from the environment. When vision is impaired in one eye during this time, also known as monocular deprivation (MD), the excitability of neurons in the visual cortex changes. But how the resting-state functional connectivity to cortical circuits beyond the visual cortex is …
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Mashup Score: 17Grandfathers-to-grandsons transgenerational transmission of exercise positive effects on cognitive performance - 5 day(s) ago
Physical exercise is a robust lifestyle intervention. Among its many benefits, it is known for its enhancement of cognitive abilities. Nevertheless, the extent to which these benefits can be transmitted across generations (intergenerational inheritance to F1, and transgenerational to F2 and beyond) remains a topic of limited comprehension. We have already shown that cognitive improvements resulting from physical exercise can be inherited from parents to their offspring, proving intergenerational effects. So, we set out to explore whether these enhancements might extend transgenerationally, impacting the F2 generation. In this study, we initially examined the behavioral traits of second-generation (F2) male mice, whose grandfathers (F0) had an exercise intervention. Our findings revealed that F2 mice with physically active F0 grandparents displayed significantly improved memory recall, encompassing both spatial and non-spatial information when compared to their counterparts from sedenta
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Mashup Score: 23
Superagers are elderly individuals with the memory ability of people 30 years younger and provide evidence that age-related cognitive decline is not inevitable. In a sample of 64 superagers (mean age 81.9; 59% women) and 55 typical older adults (mean age 82.4; 64% women) from the Vallecas Project, we studied, cross-sectionally and longitudinally over 5 years with yearly follow-ups, the global cerebral white matter status as well as region-specific white matter microstructure assessment derived from diffusivity measures. Superagers and typical older adults showed no difference in global white matter health (total white matter volume, Fazekas score, and lesions volume) cross-sectionally or longitudinally. However, analyses of diffusion parameters revealed better white matter microstructure in superagers than in typical older adults. Cross-sectional differences showed higher fractional anisotropy (FA) in superagers mostly in frontal fibres and lower mean diffusivity (MD) in most white mat
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Mashup Score: 11This Week in The Journal - 10 day(s) ago
Tyler Godat, Kendall Kohout, Keith Parkins, Qiang Yang, Juliette E. McGregor et al. (see article [e1738232024][1]) How the retina processes color is not fully understood. Retinal ganglion cells (RGCs) provide visual information to the brain, but how they combine the three types of cone
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Mashup Score: 12Spontaneous α Brain Dynamics Track the Episodic “When” - 11 day(s) ago
Across species, neurons track time over the course of seconds to minutes, which may feed the sense of time passing. Here, we asked whether neural signatures of time-tracking could be found in humans. Participants stayed quietly awake for a few minutes while being recorded with magnetoencephalography (MEG). They were unaware they would be asked how long the recording lasted (retrospective time) or instructed beforehand to estimate how long it will last (prospective timing). At rest, rhythmic brain activity is nonstationary and displays bursts of activity in the alpha range (α: 7–14 Hz). When participants were not instructed to attend to time, the relative duration of α bursts linearly predicted individuals’ retrospective estimates of how long their quiet wakefulness lasted. The relative duration of α bursts was a better predictor than α power or burst amplitude. No other rhythmic or arrhythmic activity predicted retrospective duration. However, when participants timed prospectively, the
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Mashup Score: 4
Humans need social closeness to prosper. There is evidence that empathy can induce social closeness. However, it remains unclear how empathy-related social closeness is formed and how stable it is as time passes. We applied an acquisition-extinction paradigm combined with computational modelling and fMRI, to investigate the formation and stability of empathy-related social closeness. Female participants observed painful stimulation of another person with high probability (acquisition) and low probability (extinction), and rated their closeness to that person. The results of two independent studies showed increased social closeness in the acquisition block that resisted extinction in the extinction block. Providing insights into underlying mechanisms, reinforcement learning modelling revealed that the formation of social closeness is based on a learning signal (prediction error) generated from observing another’s pain, whereas maintaining social closeness is based on a learning signal g
Source: www.jneurosci.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 21
Superagers are elderly individuals with the memory ability of people 30 years younger and provide evidence that age-related cognitive decline is not inevitable. In a sample of 64 superagers (mean age 81.9; 59% women) and 55 typical older adults (mean age 82.4; 64% women) from the Vallecas Project, we studied, cross-sectionally and longitudinally over 5 years with yearly follow-ups, the global cerebral white matter status as well as region-specific white matter microstructure assessment derived from diffusivity measures. Superagers and typical older adults showed no difference in global white matter health (total white matter volume, Fazekas score, and lesions volume) cross-sectionally or longitudinally. However, analyses of diffusion parameters revealed better white matter microstructure in superagers than in typical older adults. Cross-sectional differences showed higher fractional anisotropy (FA) in superagers mostly in frontal fibres and lower mean diffusivity (MD) in most white mat
Source: www.jneurosci.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 5
The conformational state of DNA fine-tunes the transcriptional rate and abundance of RNA. Here, we report that G-quadruplex DNA (G4-DNA) accumulates in neurons, in an experience-dependent manner, and that this is required for the transient silencing and activation of genes that are critically involved in learning and memory in male C57/BL6 mice. In addition, site-specific resolution of G4-DNA by dCas9-mediated deposition of the helicase DHX36 impairs fear extinction memory. Dynamic DNA structure states therefore represent a key molecular mechanism underlying memory consolidation. One-Sentence Summary: G4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.
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#JNeurosciAnnualSpotlight | SSRI mechanism may be more complex than we think: Nichols et al. developed new tools to investigate the accumulation & kinetics of two SSRIs in different cellular compartments. @Caltech https://t.co/6epeYvyVvt https://t.co/EhDuPKy54c