Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology

A widespread misconception in much of psychology is that (a) as vertebrate animals evolved, “newer” brain structures were added over existing “older” brain structures, and (b) these newer, more complex structures endowed animals with newer and more complex psychological functions, behavioral flexibility, and language. This belief, although widely shared in introductory psychology textbooks, has long been discredited among neurobiologists and stands in contrast to the clear and unanimous agreement on these issues among those studying nervous-system evolution. We bring psychologists up to date on this issue by describing the more accurate model of neural evolution, and we provide examples of how this inaccurate view may have impeded progress in psychology. We urge psychologists to abandon this mistaken view of human brains.

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MicroRNA profiling of the pig periaqueductal grey (PAG) region reveals candidates potentially related to sex-dependent differences

Biology of Sex Differences ◽

10.1186/s13293-020-00343-2 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Klaudia Pawlina-Tyszko ◽

Maria Oczkowicz ◽

Artur Gurgul ◽

Tomasz Szmatoła ◽

Monika Bugno-Poniewierska

Keyword(s):

Expression Profiles ◽

Differential Expression Analysis ◽

Mirna Profile ◽

Human Model ◽

Periaqueductal Grey ◽

Neurological Research ◽

Downstream Analysis ◽

Neuron Growth ◽

Human Brains ◽

The Brain

Abstract Background MicroRNAs indirectly orchestrate myriads of essential biological processes. A wide diversity of miRNAs of the neurodevelopmental importance characterizes the brain tissue, which, however, exhibits region-specific miRNA profile differences. One of the most conservative regions of the brain is periaqueductal grey (PAG) playing vital roles in significant functions of this organ, also those observed to be sex-influenced. The domestic pig is an important livestock species but is also believed to be an excellent human model. This is of particular importance for neurological research because of the similarity of pig and human brains as well as difficult access to human samples. However, the pig PAG profile has not been characterized so far. Moreover, molecular bases of sex differences connected with brain functioning, including miRNA expression profiles, have not been fully deciphered yet. Methods Thus, in this study, we applied next-generation sequencing to characterize pig PAG expressed microRNAs. Furthermore, we performed differential expression analysis between females and males to identify changes of the miRNA profile and reveal candidates underlying sex-related differences. Results As a result, known brain-enriched, and new miRNAs which will expand the available profile, were identified. The downstream analysis revealed 38 miRNAs being differentially expressed (DE) between female and male samples. Subsequent pathway analysis showed that they enrich processes vital for neuron growth and functioning, such as long-term depression and axon guidance. Among the identified sex-influenced miRNAs were also those associated with the PAG physiology and diseases related to this region. Conclusions The obtained results broaden the knowledge on the porcine PAG miRNAome, along with its dynamism reflected in different isomiR signatures. Moreover, they indicate possible mechanisms associated with sex-influenced differences mediated via miRNAs in the PAG functioning. They also provide candidate miRNAs for further research concerning, i.e., sex-related bases of physiological and pathological processes occurring in the nervous system. Graphical abstract

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Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

International Journal of Molecular Sciences ◽

10.3390/ijms22136858 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6858

Author(s):

Fanny Gaudel ◽

Gaëlle Guiraudie-Capraz ◽

François Féron

Keyword(s):

G Proteins ◽

The Body ◽

Trace Amines ◽

Chemical Senses ◽

Brain Areas ◽

Genes Encoding ◽

The Central Nervous System ◽

Human Brains ◽

The Brain ◽

Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

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Clues to why human brains grow so large

The New Scientist ◽

10.1016/s0262-4079(21)00555-8 ◽

2021 ◽

Vol 250 (3328) ◽

pp. 20

Author(s):

KS

Keyword(s):

Human Brains

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Multiplexed neurochemical transmission emulated using a dual-excitatory synaptic transistor

npj 2D Materials and Applications ◽

10.1038/s41699-021-00205-4 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Mingxue Ma ◽

Yao Ni ◽

Zirong Chi ◽

Wanqing Meng ◽

Haiyang Yu ◽

...

Keyword(s):

Neural Network ◽

Central Nervous System ◽

Nervous System ◽

Long Term Potentiation ◽

Short Term ◽

Term Potentiation ◽

Binary Neural Network ◽

Neuromorphic Systems ◽

Human Brains

AbstractThe ability to emulate multiplexed neurochemical transmission is an important step toward mimicking complex brain activities. Glutamate and dopamine are neurotransmitters that regulate thinking and impulse signals independently or synergistically. However, emulation of such simultaneous neurotransmission is still challenging. Here we report design and fabrication of synaptic transistor that emulates multiplexed neurochemical transmission of glutamate and dopamine. The device can perform glutamate-induced long-term potentiation, dopamine-induced short-term potentiation, or co-release-induced depression under particular stimulus patterns. More importantly, a balanced ternary system that uses our ambipolar synaptic device backtrack input ‘true’, ‘false’ and ‘unknown’ logic signals; this process is more similar to the information processing in human brains than a traditional binary neural network. This work provides new insight for neuromorphic systems to establish new principles to reproduce the complexity of a mammalian central nervous system from simple basic units.

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Gaze-pattern similarity at encoding may interfere with future memory

Scientific Reports ◽

10.1038/s41598-021-87258-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nathalie klein Selle ◽

Matthias Gamer ◽

Yoni Pertzov

Keyword(s):

Interference Effect ◽

Directed Forgetting ◽

Visual Input ◽

Pink Noise ◽

Memory Traces ◽

Gaze Patterns ◽

Pattern Similarity ◽

Memory Control ◽

Human Brains ◽

The Way

AbstractHuman brains have a remarkable ability to separate streams of visual input into distinct memory-traces. It is unclear, however, how this ability relates to the way these inputs are explored via unique gaze-patterns. Moreover, it is yet unknown how motivation to forget or remember influences the link between gaze similarity and memory. In two experiments, we used a modified directed-forgetting paradigm and either showed blurred versions of the encoded scenes (Experiment 1) or pink noise images (Experiment 2) during attempted memory control. Both experiments demonstrated that higher levels of across-stimulus gaze similarity relate to worse future memory. Although this across-stimulus interference effect was unaffected by motivation, it depended on the perceptual overlap between stimuli and was more pronounced for different scene comparisons, than scene–pink noise comparisons. Intriguingly, these findings echo the pattern similarity effects from the neuroimaging literature and pinpoint a mechanism that could aid the regulation of unwanted memories.

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Protein farnesylation is upregulated in Alzheimer’s human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer’s model mice

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01231-5 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Angela Jeong ◽

Shaowu Cheng ◽

Rui Zhong ◽

David A. Bennett ◽

Martin O. Bergö ◽

...

Keyword(s):

Cognitive Impairment ◽

Small Gtpases ◽

Specific Role ◽

Postmortem Brain ◽

Effective Prevention ◽

Postmortem Brain Tissue ◽

Mtorc1 Signaling ◽

Behavioral Assessments ◽

Human Brains

AbstractThe pathogenic mechanisms underlying the development of Alzheimer’s disease (AD) remain elusive and to date there are no effective prevention or treatment for AD. Farnesyltransferase (FT) catalyzes a key posttranslational modification process called farnesylation, in which the isoprenoid farnesyl pyrophosphate is attached to target proteins, facilitating their membrane localization and their interactions with downstream effectors. Farnesylated proteins, including the Ras superfamily of small GTPases, are involved in regulating diverse physiological and pathological processes. Emerging evidence suggests that isoprenoids and farnesylated proteins may play an important role in the pathogenesis of AD. However, the dynamics of FT and protein farnesylation in human brains and the specific role of neuronal FT in the pathogenic progression of AD are not known. Here, using postmortem brain tissue from individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), or Alzheimer’s dementia, we found that the levels of FT and membrane-associated H-Ras, an exclusively farnesylated protein, and its downstream effector ERK were markedly increased in AD and MCI compared with NCI. To elucidate the specific role of neuronal FT in AD pathogenesis, we generated the transgenic AD model APP/PS1 mice with forebrain neuron-specific FT knockout, followed by a battery of behavioral assessments, biochemical assays, and unbiased transcriptomic analysis. Our results showed that the neuronal FT deletion mitigates memory impairment and amyloid neuropathology in APP/PS1 mice through suppressing amyloid generation and reversing the pathogenic hyperactivation of mTORC1 signaling. These findings suggest that aberrant upregulation of protein farnesylation is an early driving force in the pathogenic cascade of AD and that targeting FT or its downstream signaling pathways presents a viable therapeutic strategy against AD.

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