scholarly journals Oxytocin receptor binding in the titi monkey hippocampal formation is associated with parental status and partner affiliation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander Baxter ◽  
M. Anderson ◽  
A. M. Seelke ◽  
E. L. Kinnally ◽  
S. M. Freeman ◽  
...  
Keyword(s):  
Hippocampal Formation ◽  
Average Frequency ◽  
Postmortem Brain ◽  
Primate Species ◽  
Pair Bonding ◽  
Infant Carrying ◽  
Titi Monkey ◽  
Postmortem Brain Tissue ◽  
Titi Monkeys ◽  
The Impact

Abstract Social cognition is facilitated by oxytocin receptors (OXTR) in the hippocampus, a brain region that changes dynamically with pregnancy, parturition, and parenting experience. We investigated the impact of parenthood on hippocampal OXTR in male and female titi monkeys, a pair-bonding primate species that exhibits biparental care of offspring. We hypothesized that in postmortem brain tissue, OXTR binding in the hippocampal formation would differ between parents and non-parents, and that OXTR density would correlate with frequencies of observed parenting and affiliative behaviors between partners. Subjects were 10 adult titi monkeys. OXTR binding in the hippocampus (CA1, CA2/3, CA4, dentate gyrus, subiculum) and presubiculum layers (PSB1, PSB3) was determined using receptor autoradiography. The average frequency of partner affiliation (Proximity, Contact, and Tail Twining) and infant carrying were determined from longitudinal observations (5–6 per day). Analyses showed that parents exhibited higher OXTR binding than non-parents in PSB1 (t(8) = − 2.33, p = 0.048), and that OXTR binding in the total presubiculm correlated negatively with Proximity (r = − 0.88) and Contact (r = − 0.91), but not Tail Twining or infant carrying. These results suggest that OXTR binding in the presubiculum supports pair bonding and parenting behavior, potentially by mediating changes in hippocampal plasticity.

scholarly journals Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
John F. Fullard ◽  
Hao-Chih Lee ◽  
Georgios Voloudakis ◽  
Shengbao Suo ◽  
Behnam Javidfar ◽  
...  
Keyword(s):  
Immune Response ◽  
Choroid Plexus ◽  
Transcriptome Analysis ◽  
Brain Regions ◽  
Postmortem Brain ◽  
Network Analyses ◽  
Postmortem Brain Tissue ◽  
Single Nucleus ◽  
The Impact ◽  
The Brain

Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation, and host immune response in acute COVID-19 cases. Methods Three brain regions (dorsolateral prefrontal cortex, medulla oblongata, and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of the virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering > 99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain. Results Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes, and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory, and gene regulatory network analyses revealed transcriptional changes in the cortical microglia associated with a range of biological processes, including cellular activation, mobility, and phagocytosis. Conclusions Despite the absence of detectable SARS-CoV-2 in the brain at the time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.

scholarly journals Prospects of Genetics and Epigenetics of Alcohol Use Disorder

2020 ◽  
Vol 7 (4) ◽  
pp. 446-452
Author(s):  
Friederike Wedemeyer ◽  
Jakob A. Kaminski ◽  
Lea Zillich ◽  
Alisha S. M. Hall ◽  
Eva Friedel ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Disease Classification ◽  
Postmortem Brain ◽  
Ongoing Research ◽  
Postmortem Brain Tissue ◽  
The Future ◽  
Future Direction ◽  
The Impact ◽  
Insight Into

Abstract Purpose of Review In this study, we illustrate recent findings regarding the genetics and epigenetics of alcohol use disorder (AUD). We further outline the future direction of genetic and epigenetic research in AUD. Recent Findings Recent genome- and epigenome-wide studies allow new insight into genetic and epigenetic variation associated with AUD. The largest EWAS of AUD so far/to date found evidence for altered glucocorticoid receptor regulation. Longitudinal studies provide insight into the dynamics of the disease. Analyses of postmortem brain tissue reveal the impact of chronic alcohol consumption on DNA methylation in the brain. Summary Genetic and environmental factors—mediated via epigenetic mechanisms—play an important role in AUD. Although knowledge of the biological underpinnings of AUD is still limited, ongoing research will ultimately lead to the development of biomarkers for disease classification, course of disease, and treatment response to support personalized medicine in the future.

scholarly journals Neurodegeneration Induced by Anti-IgLON5 Antibodies Studied in Induced Pluripotent Stem Cell-Derived Human Neurons

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 837
Author(s):  
Matias Ryding ◽  
Mattias Gamre ◽  
Mette S. Nissen ◽  
Anna C. Nilsson ◽  
Justyna Okarmus ◽  
...  
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Neuronal Cell ◽  
Induced Pluripotent Stem Cell ◽  
Synaptic Proteins ◽  
Postmortem Brain ◽  
Human Neurons ◽  
Postmortem Brain Tissue ◽  
The Impact

Anti-IgLON5 disease is a progressive neurological disorder associated with autoantibodies against a neuronal cell adhesion molecule, IgLON5. In human postmortem brain tissue, the neurodegeneration and accumulation of hyperphosphorylated tau (p-tau) are found. Whether IgLON5 antibodies induce neurodegeneration or neurodegeneration provokes an immune response causing inflammation and antibody formation remains to be elucidated. We investigated the effects of anti-IgLON5 antibodies on human neurons. Human neural stem cells were differentiated for 14–48 days and exposed from Days 9 to 14 (short-term) or Days 13 to 48 (long-term) to either (i) IgG from a patient with confirmed anti-IgLON5 antibodies or (ii) IgG from healthy controls. The electrical activity of neurons was quantified using multielectrode array assays. Cultures were immunostained for β-tubulin III and p-tau and counterstained with 4′,6-Diamidine-2′-phenylindole dihydrochloride (DAPI). To study the impact on synapses, cultures were also immunostained for the synaptic proteins postsynaptic density protein 95 (PSD95) and synaptophysin. A lactate dehydrogenase release assay and nuclei morphology analysis were used to assess cell viability. Cultures exposed to anti-IgLON5 antibodies showed reduced neuronal spike rate and synaptic protein content, and the proportion of neurons with degenerative appearance including p-tau (T205)-positive neurons was higher when compared to cultures exposed to control IgG. In addition, cell death was increased in cultures exposed to anti-IgLON5 IgG for 21 days. In conclusion, pathological anti-IgLON5 antibodies induce neurodegenerative changes and cell death in human neurons. This supports the hypothesis that autoantibodies may induce the neurodegenerative changes found in patients with anti-IgLON5-mediated disease. Furthermore, this study highlights the potential use of stem cell-based in vitro models for investigations of antibody-mediated diseases. As anti-IgLON5 disease is heterogeneous, more studies with different IgLON5 antibody samples tested on human neurons are needed.

scholarly journals Single-Cell RNA Sequencing in Parkinson’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 368
Author(s):  
Shi-Xun Ma ◽  
Su Bin Lim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Rna Degradation ◽  
Postmortem Brain ◽  
Cell Type ◽  
New Findings ◽  
Postmortem Brain Tissue ◽  
Technical Challenges

Single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global view of cellular composition and phenotype of PD at the single-cell resolution. Here, we reviewed recent sc/snRNA-seq efforts that have successfully characterized diverse cell-type populations and identified cell type-specific disease associations in PD. We also examined how these studies have employed computational and analytical tools to analyze and interpret the rich information derived from sc/snRNA-seq. Finally, we highlighted important limitations and emerging technologies for addressing key technical challenges currently limiting the integration of new findings into clinical practice.

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

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.

scholarly journals Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Preeti Singh ◽  
Peter S. Hanson ◽  
Christopher M. Morris
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Neural Cells ◽  
Compensatory Mechanism ◽  
Postmortem Brain Tissue ◽  
Lysine Deacetylases ◽  
Neuronal Stress

Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson’s disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along withα-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation ofα-synuclein aggregates but showed minimal colocalisation withα-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress.

scholarly journals The use of disturbed and undisturbed forest by masked titi monkeys Callicebus personatus melanochir is proportional to food availability

Oryx ◽  
2002 ◽  
Vol 36 (2) ◽  
pp. 133-139 ◽  
Author(s):  
Stefanie Heiduck
Keyword(s):  
Home Range ◽  
Atlantic Rainforest ◽  
Forest Types ◽  
Clear Cut ◽  
Titi Monkey ◽  
Eastern Brazil ◽  
Titi Monkeys ◽  
Undisturbed Forest ◽  
Disturbed Forest ◽  
One Year

The masked titi Callicebus personatus melanochir is a threatened primate, endemic to the Atlantic rainforest of eastern Brazil. The Atlantic rainforest has been reduced to only 5% of its former extent, and only 2% consists of undisturbed forest. The survival of the masked titi monkey is therefore dependent on its ability to utilise disturbed forest habitat. A group of four masked titi monkeys was observed for one year in a plot that contained both disturbed and undisturbed forest. The group used a home range of 22 ha, which comprised 58% undisturbed forest, 31% selectively logged forest and 11% forest that was regrowing after a clear-cut. The titi monkeys did not use the different forest types in proportion to the availability of each within their home range: undisturbed forest was used more than expected from its proportional availability, and disturbed forest was used less than expected. Use of forest types appeared to be determined by the availability of food resources. Undisturbed forest had the most food per unit area and regrowing forest had the least. This study shows that masked titi monkeys may be able to survive in disturbed forest habitats if these areas are of high enough quality to contain sufficient food and other resources.

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