scholarly journals Prenatal stress programs behavioral pattern separation in adult mice

2022 ◽  
Author(s):  
Samyutha Rajendran ◽  
Mohamed-Lyes Kaci ◽  
Elodie Ladeveze ◽  
Nora Abrous ◽  
Muriel Koehl

Stress is an unavoidable condition in human life. Stressful events experienced during development, including in utero, have been suggested as one major pathophysiological mechanism for developing vulnerability towards neuropsychiatric and neurodevelopmental disorders in adulthood. One cardinal feature of such disorders is impaired cognitive ability, which may in part rely on abnormal structure and function of the hippocampus. In the hippocampus, the dentate gyrus is a site of continuous neurogenesis, a process that has been recently implicated in spatial pattern separation, a cognitive phenomenon that serves to reduce the degree of overlap in the incoming information to facilitate its storage with minimal interference. We previously reported that adult neurogenesis is altered by prenatal stress allowing us to hypothesize that prenatal stress may possibly lead to impairment in pattern separation. To test this hypothesis, both control (C) and prenatally stressed (PS) adult mice were tested for metric and contextual discrimination abilities. We report for the first time that prenatal stress impairs pattern separation process, a deficit that may underlie their cognitive alterations and that may result in defective behaviors reminiscent of psychiatric illness such as post-traumatic stress disorder.

Metahumaniora ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 54
Author(s):  
Erlina Zulkifli Mahmud ◽  
Taufik Ampera ◽  
Yuyu Yohana Risagarniwa ◽  
Inu Isnaeni Sidiq

Kedudukan dan fungsi bahasa sebagai alat komunikasi manusia mencakup seluruh bidang kehidupan termasuk ilmu pengetahuan antara lain terkait sejarah peradaban manusia; bagaimana manusia mempertahankan hidupnya, bagaimana manusia memperlakukan alam, bagaimana alam menyediakan segala kebutuhan manusia. Apa yang dilakukan manusia saat ini, saat lampau, dan apa yang dilakukan manusia jauh di masa prasejarah, bagaimana kondisi alam di masa-masa tersebut, apa perubahan dan perkembangannya, dapat didokumentasikan melalui bahasa, divisualisasikan kembali, lalu dipajang sebagai salah satu upaya konversai dan preservasi dalam satu institusi yang disebut museum. Penelitian ini membahas kedudukan dan fungsi bahasa dalam permuseuman. Bagaimana kedudukan dan fungsi bahasa dalam permuseuman baik dalam informasi yang disampaikan oleh pemandu wisata museumnya maupun yang terpajang menyertai benda-benda dan gambar-gambar merupakan tujuan dari penelitian ini. Metode penelitian yang digunakan adalah gabungan antara metode lapangan dan metode literatur. Hasil penelitian menunjukkan bahwa secara umum kedudukan bahasa Indonesia berada pada urutan pertama setelah Bahasa Inggris dan keberadaan kedua bahasa dalam permuseuman ini melibatkan dua fungsi utama bahasa, yakni fungsi komunikatif dan fungsi informatif.The existence and function of language  as a medium of communication covers all fields of human life including knowledge, one of them is the history of human civilization; how humans survived, how human utilized nature for their lives, and how nature provides all the necessities for humans. What humans have been doing now, what they have done in the past and far before that in the pre-history time, how the conditions of the nature at those times were and what changes as well as progresses occurred are documented using language, then re-visualized,  displayed as one of conservation and preservation acts in an institution called museum. This research discusess the existence and function of language in museums. How important the existence of a language in museums and what language functions used in museums both in informations given by the museum guides and on the displays accompanying objects and pictures are the aims of this research. The methods used are the combination between field research and library research. The results show that generally the existence of Indonesian language plays more important role than English and both languages have two main functions; communicative function and informative function.     


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 120-121
Author(s):  
Chloey P Guy ◽  
Catherine L Wellman ◽  
David G Riley ◽  
Charles R Long ◽  
Ron D Randel ◽  
...  

Abstract We previously determined that prenatal stress (PNS) differentially affected methylation of DNA from leukocytes of 28-d-old calves. Specifically, COX14 (cytochrome c oxidase (COX) assembly factor) and CKMT1B (mitochondrial creatine kinase U-type) were hypomethylated and COA5 (COX assembly factor 5), COX5A (COX subunit 5A), NRF1 (nuclear respiratory factor 1), and GSST1 (glutathione S-transferase theta-1) were hypermethylated in PNS compared to non-PNS calves (P ≤ 0.05). Our current objective was to test the hypothesis that PNS exhibit impaired mitochondrial function and greater oxidative stress than non-PNS calves. Blood and longissimus dorsi muscle samples were collected from yearling Brahman calves whose mothers were stressed by 2 h transportation at 60, 80, 100, 120, and 140 days of gestation (PNS; 8 bulls, 6 heifers) and non-PNS calves (4 bulls, 6 heifers). Serum was evaluated for the stress hormone, cortisol, and muscle damage marker, creatine kinase; muscle was analyzed for mitochondrial volume density and function by citrate synthase (CS) and COX activities, respectively, concentration of malondialdehyde, a lipid peroxidation marker, and activity of the antioxidant, superoxide dismutase (SOD). Data were analyzed using mixed linear models with treatment and sex as fixed effects. Serum cortisol was numerically higher in PNS than non-PNS calves but was not statistically different. Muscle CS and COX activities relative to protein were greater in PNS than non-PNS calves (P ≤ 0.03), but COX relative to CS activity was similar between groups. Activity of COX was greater in bulls than heifers (P = 0.03), but no other measure was affected by sex. All other measures were unaffected by PNS. Prenatal stress did not affect markers of muscle damage and oxidative stress in yearling Brahman calves at rest but mitochondrial volume density and function were greater in PNS calves. Acute stressors induce oxidative stress, so implications of differences in mitochondria in PNS calves following a stressor should be investigated.


Author(s):  
Fei Wang ◽  
Qianqian Wang ◽  
Baowei Liu ◽  
Lisheng Mei ◽  
Sisi Ma ◽  
...  

AbstractThe brain is known to express many long noncoding RNAs (lncRNAs); however, whether and how these lncRNAs function in modulating synaptic stability remains unclear. Here, we report a cerebellum highly expressed lncRNA, Synage, regulating synaptic stability via at least two mechanisms. One is through the function of Synage as a sponge for the microRNA miR-325-3p, to regulate expression of the known cerebellar synapse organizer Cbln1. The other function is to serve as a scaffold for organizing the assembly of the LRP1-HSP90AA1-PSD-95 complex in PF-PC synapses. Although somewhat divergent in its mature mRNA sequence, the locus encoding Synage is positioned adjacent to the Cbln1 loci in mouse, rhesus macaque, and human, and Synage is highly expressed in the cerebella of all three species. Synage deletion causes a full-spectrum cerebellar ablation phenotype that proceeds from cerebellar atrophy, through neuron loss, on to synapse density reduction, synaptic vesicle loss, and finally to a reduction in synaptic activity during cerebellar development; these deficits are accompanied by motor dysfunction in adult mice, which can be rescued by AAV-mediated Synage overexpression from birth. Thus, our study demonstrates roles for the lncRNA Synage in regulating synaptic stability and function during cerebellar development.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Peng Chen ◽  
Hongyang Jing ◽  
Mingtao Xiong ◽  
Qian Zhang ◽  
Dong Lin ◽  
...  

AbstractThe genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1–LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.


2006 ◽  
Vol 80 (22) ◽  
pp. 11355-11361 ◽  
Author(s):  
Shirin Kordasti ◽  
Claudia Istrate ◽  
Mahanez Banasaz ◽  
Martin Rottenberg ◽  
Henrik Sjövall ◽  
...  

ABSTRACT In contrast to humans, adult but not infant small animals are resistant to rotavirus diarrhea. The pathophysiological mechanism behind this age-restricted diarrhea is currently unresolved, and this question was investigated by studying the secretory state of the small intestines of adult mice infected with rotavirus. Immunohistochemistry and histological examinations revealed that rotavirus (strain EDIM) infects all parts of the small intestines of adult mice, with significant numbers of infected cells in the ilea at 2 and 4 days postinfection. Furthermore, quantitative PCR revealed that 100-fold more viral RNA was produced in the ilea than in the jejuna or duodena of adult mice. In vitro perfusion experiments of the small intestine did not reveal any significant changes in net fluid secretion among mice infected for 3 days or 4 days or in those that were noninfected (37 ± 9 μl · h−1 · cm−1, 22 ± 13 μl · h−1 · cm−1, and 33 ± 6 μl · h−1 · cm−1, respectively) or in transmucosal potential difference (4.0 ± 0.3 mV versus 3.9 ± 0.4 mV), a marker for active chloride secretion, between control and rotavirus-infected mice. In vivo experiments also did not show any differences in potential difference between uninfected and infected small intestines. Furthermore, no significant differences in weight between infected and uninfected small intestines were found, nor were any differences in fecal output observed between infected and control mice. Altogether, these data suggest that rotavirus infection is not sufficient to stimulate chloride and water secretion from the small intestines of adult mice.


Hippocampus ◽  
2012 ◽  
Vol 22 (9) ◽  
pp. 1826-1832 ◽  
Author(s):  
Heather M. Holden ◽  
Calhuei Hoebel ◽  
Kelly Loftis ◽  
Paul E. Gilbert

Author(s):  
Erin K. Crowley ◽  
Stefanie Grabrucker ◽  
Caitriona M. Long-Smith ◽  
Alice Stack ◽  
Denise M. O'Gorman ◽  
...  

Author(s):  
Kaitlyn Barton

Rapid advancements in radical life extension technologies contribute to humanity’s ever-changing world. The normalization of radical life extension technologies would signify that the present era in which biology and evolution act as dictators of human life and health would come to an end, thereby ushering in the age of the post-human. The purpose of this paper is to engage in a theological analysis of how and to what degree the ways in which humanity speaks about God could be changed or influenced if radical life extension becomes normative within society. . It is likely that this powerful technology would have a significant impact on many facets of culture, including the way in which humanity engages with religion, in particular Christianity. To accomplish this, the technology that could potentially support radical life extension, namely nanotechnology and cybernetic immortality, will be explained in terms of their relevance and function. Subsequently, the affects of radical life extension for human life will be addressed. Specifically, the implications of the partial or full eradication of human biological and psychological suffering and death through the use of cybernetic immortality and nanotechnology and will be considered. From there, the core theological concepts and narratives will be analyzed in the context of the potential actualization of radical life extension technology. A focus will be placed on the ethic of loving thy neighbour, Christ’s suffering on the cross, the hope of salvation and the Christian hope of entrance into heaven after death. 


PLoS Biology ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. e3001350
Author(s):  
Diana Fernández-Suárez ◽  
Favio A. Krapacher ◽  
Katarzyna Pietrajtis ◽  
Annika Andersson ◽  
Lilian Kisiswa ◽  
...  

The medial habenula (mHb) is an understudied small brain nucleus linking forebrain and midbrain structures controlling anxiety and fear behaviors. The mechanisms that maintain the structural and functional integrity of mHb neurons and their synapses remain unknown. Using spatiotemporally controlled Cre-mediated recombination in adult mice, we found that the glial cell–derived neurotrophic factor receptor alpha 1 (GFRα1) is required in adult mHb neurons for synaptic stability and function. mHb neurons express some of the highest levels of GFRα1 in the mouse brain, and acute ablation of GFRα1 results in loss of septohabenular and habenulointerpeduncular glutamatergic synapses, with the remaining synapses displaying reduced numbers of presynaptic vesicles. Chemo- and optogenetic studies in mice lacking GFRα1 revealed impaired circuit connectivity, reduced AMPA receptor postsynaptic currents, and abnormally low rectification index (R.I.) of AMPARs, suggesting reduced Ca2+ permeability. Further biochemical and proximity ligation assay (PLA) studies defined the presence of GluA1/GluA2 (Ca2+ impermeable) as well as GluA1/GluA4 (Ca2+ permeable) AMPAR complexes in mHb neurons, as well as clear differences in the levels and association of AMPAR subunits with mHb neurons lacking GFRα1. Finally, acute loss of GFRα1 in adult mHb neurons reduced anxiety-like behavior and potentiated context-based fear responses, phenocopying the effects of lesions to septal projections to the mHb. These results uncover an unexpected function for GFRα1 in the maintenance and function of adult glutamatergic synapses and reveal a potential new mechanism for regulating synaptic plasticity in the septohabenulointerpeduncular pathway and attuning of anxiety and fear behaviors.


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