Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Individual Variability in Animal Models of Psychopathologies
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Individual Variability in Animal Models of Psychopathologies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 14320

Special Issue Editor

Prof. Gal Richter-Levin

E-Mail Website
Guest Editor
Department of Psychology, Sagol Department of Neurobiology, The Integrated Brain And Behavior,Research Center (IBBRC), University of Haifa, Haifa, 3498838 Israel
Interests: Behavioral Neuroscience; Neurobiology of Stress and trauma-related psychopathologies; Stress; PTSD; Mood disorders; Animal models of psychopathologies

Special Issue Information

Dear Colleagues,

Animal models of psychopathologies are expected to be instrumental in identifying neural, physiological, and molecular mechanisms of those disorders, with the aim of translating such knowledge into novel drugs and treatments. Traditionally, the analysis of results is based on comparing group averages which, however, mask individual variability. In fact, a hallmark of psychopathologies is the large individual variability in response to challenges, in symptoms, and, apparently, also in the underlying biological mechanisms. These categorizations, which cannot be studied by group averages, are critical to develop effective personalized medicine approaches to psychopathologies. Novel experimental settings and analysis approaches are needed.   

This Special Issue of the International Journal of Molecular Sciences entitled “Individual Variability in Animal Models of Psychopathologies” will focus on the molecular aspects related to the development of such novel approaches that, instead of aiming to reduce or mask individual variability, take it into consideration and analyze molecular results accordingly. Contributions on this topic are welcome, including original research articles and reviews. We also very much welcome submissions from postdocs, PhD students, and young researchers.

Prof. Gal Richter-Levin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Individual variability
  • Personalized medicine
  • Animal models
  • Mood disorders
  • PTSD
  • Anxiety
  • Social behavior disorders
  • Agression
  • Stress
  • Stress Resilience

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

27 pages, 2919 KiB  
Article
The Role of Microglia in the (Mal)adaptive Response to Traumatic Experience in an Animal Model of PTSD
by Kesem Nahum, Doron Todder, Joseph Zohar and Hagit Cohen
Int. J. Mol. Sci. 2022, 23(13), 7185; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137185 - 28 Jun 2022
Cited by 9 | Viewed by 1759
Abstract
The present study investigates whether predator scent-stress (PSS) shifts the microglia from a quiescent to a chronically activated state and whether morphological alterations in microglial activation differ between individuals displaying resilient vs. vulnerable phenotypes. In addition, we examined the role that GC receptors [...] Read more.
The present study investigates whether predator scent-stress (PSS) shifts the microglia from a quiescent to a chronically activated state and whether morphological alterations in microglial activation differ between individuals displaying resilient vs. vulnerable phenotypes. In addition, we examined the role that GC receptors play during PSS exposure in the impairment of microglial activation and thus in behavioral response. Adult male Sprague Dawley rats were exposed to PSS or sham-PSS for 15 min. Behaviors were assessed with the elevated plus-maze (EPM) and acoustic startle response (ASR) paradigms 7 days later. Localized brain expression of Iba-1 was assessed, visualized, and classified based on their morphology and stereological counted. Hydrocortisone and RU486 were administered systemically 10 min post PSS exposure and behavioral responses were measured on day 7 and hippocampal expression of Ionized calcium-binding adaptor molecule 1 (Iba-1) was subsequently evaluated. Animals whose behavior was extremely disrupted (PTSD-phenotype) selectively displayed excessive expression of Iba-1 with concomitant downregulation in the expression of CX3C chemokine receptor 1 (CX3CR1) in hippocampal structures as compared with rats whose behavior was minimally or partially disrupted. Changes in microglial morphology have also been related only to the PTSD-phenotype group. These data indicate that PSS-induced microglia activation in the hippocampus serves as a critical mechanistic link between the HPA-axis and PSS-induced impairment in behavioral responses. Full article
(This article belongs to the Special Issue Individual Variability in Animal Models of Psychopathologies)
►▼ Show Figures

Figure 1

17 pages, 2855 KiB  
Article
Variability in Behavioral Phenotypes after Forced Swimming-Induced Stress in Rats Is Associated with Expression of the Glucocorticoid Receptor, Nurr1, and IL-1β in the Hippocampus
by Elizabeth Ruiz-Sánchez, Arely M. López-Ramírez, Ángel Ruiz-Chow, Minerva Calvillo, Aldo A. Reséndiz-Albor, Brenda Anguiano and Patricia Rojas
Int. J. Mol. Sci. 2021, 22(23), 12700; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312700 - 24 Nov 2021
Cited by 3 | Viewed by 1640
Abstract
Individual differences in coping with stress may determine either a vulnerable or resilient phenotype. Therefore, it is important to better understand the biology underlying the behavioral phenotype. We assessed whether individual behavioral phenotype to acute stress is related with the hippocampal expression of [...] Read more.
Individual differences in coping with stress may determine either a vulnerable or resilient phenotype. Therefore, it is important to better understand the biology underlying the behavioral phenotype. We assessed whether individual behavioral phenotype to acute stress is related with the hippocampal expression of glucocorticoid receptor (GR), Nurr1, interleukin-1 beta (IL-1β) or brain-derived neurotrophic factor (BDNF). Wistar male rats were exposed to forced swimming for 15 min and sacrificed at different times. Behavioral response was analyzed, and it was compared with the gene and protein expression of GR, Nurr1, IL-1β and BDNF in the hippocampus for each time point. Behavioral phenotyping showed a group with high immobility (vulnerable) while another had low immobility (resilient). No significant differences were found in the Nurr1, IL-1β and BDNF mRNA levels between resilient and vulnerable rats at different recovery times except for Nr3c1 (gene for GR). However, exposure to stress caused significantly higher levels of GR, Nurr1 and IL-1β proteins of vulnerable compared to resilient rats. This variability of behavioral phenotypes is associated with a differential molecular response to stress that involves GR, Nurr1, and IL-1β as mediators in coping with stress. This contributes to identifying biomarkers of susceptibility to stress. Full article
(This article belongs to the Special Issue Individual Variability in Animal Models of Psychopathologies)
►▼ Show Figures

Figure 1

28 pages, 8848 KiB  
Article
Fear Extinction and Predictive Trait-Like Inter-Individual Differences in Rats Lacking the Serotonin Transporter
by Maria Willadsen, Metin Uengoer, Anna Sługocka, Rainer K.W. Schwarting, Judith R. Homberg and Markus Wöhr
Int. J. Mol. Sci. 2021, 22(13), 7088; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137088 - 30 Jun 2021
Cited by 9 | Viewed by 2289
Abstract
Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT [...] Read more.
Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT deficiency on fear extinction in a differential fear conditioning paradigm in male and female rats. Fear-related behavior displayed during acquisition, extinction, and recovery, was measured through quantification of immobility and alarm 22-kHz ultrasonic vocalizations (USV). Trait-like inter-individual differences in novelty-seeking, anxiety-related behavior, habituation learning, cognitive performance, and pain sensitivity were examined for their predictive value in forecasting fear extinction. Our results show that SERT deficiency strongly affected the emission of 22-kHz USV during differential fear conditioning. During acquisition, extinction, and recovery, SERT deficiency consistently led to a reduction in 22-kHz USV emission. While SERT deficiency did not affect immobility during acquisition, genotype differences started to emerge during extinction, and during recovery rats lacking SERT showed higher levels of immobility than wildtype littermate controls. Recovery was reflected in increased levels of immobility but not 22-kHz USV emission. Prominent sex differences were evident. Among several measures for trait-like inter-individual differences, anxiety-related behavior had the best predictive quality. Full article
(This article belongs to the Special Issue Individual Variability in Animal Models of Psychopathologies)
►▼ Show Figures

Graphical abstract

13 pages, 1768 KiB  
Article
Is PTSD-Phenotype Associated with HPA-Axis Sensitivity?: The Endocannabinoid System in Modulating Stress Response in Rats
by Dor Danan, Doron Todder, Joseph Zohar and Hagit Cohen
Int. J. Mol. Sci. 2021, 22(12), 6416; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126416 - 15 Jun 2021
Cited by 5 | Viewed by 1908
Abstract
Endocannabinoids play a role in adaptation to stress and regulate the release of glucocorticoids in stressed and unstressed conditions. We recently found that basal corticosterone pulsatility may significantly impact the vulnerability for developing post-traumatic-stress-disorder (PTSD), suggesting that the endocannabinoid system may contribute to [...] Read more.
Endocannabinoids play a role in adaptation to stress and regulate the release of glucocorticoids in stressed and unstressed conditions. We recently found that basal corticosterone pulsatility may significantly impact the vulnerability for developing post-traumatic-stress-disorder (PTSD), suggesting that the endocannabinoid system may contribute to its development. To examine this, we exposed rats to predator scent stress (PSS). Behavioral reactions were recorded seven days post-PSS. Cerebrospinal fluid (CSF) was collected from anesthetized rats shortly after PSS exposure to determine the levels of 2-arachidonoyl glycerol (2-AG) and anandamide (AEA). To correlate between endocannabinoids and corticosterone levels, rats were placed in metabolic cages for urine collection. To assess the levels of endocannabinoids in specific brain regions, rats’ brains were harvested one day after behavioral analysis for staining and fluorescence quantification. Moreover, 2-AG was elevated in the CSF of PTSD-phenotype rats as compared with other groups and was inversely correlated with corticosterone urinary secretion. Eight days post-PSS exposure, hippocampal and hypothalamic 2-AG levels and hippocampal AEA levels were significantly more reduced in the PTSD-phenotype group compared to other groups. We posit that maladaptation to stress, which is propagated by an abnormal activation of endocannabinoids, mediates the subsequent stress-induced behavioral disruption, which, later, reduces neuronal the expression of endocannabinoids, contributing to PTSD symptomology. Full article
(This article belongs to the Special Issue Individual Variability in Animal Models of Psychopathologies)
►▼ Show Figures

Figure 1

29 pages, 4418 KiB  
Article
Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics
by Dor Danan, Doron Todder, Joseph Zohar and Hagit Cohen
Int. J. Mol. Sci. 2021, 22(11), 6050; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116050 - 03 Jun 2021
Cited by 9 | Viewed by 2688
Abstract
Previously, we found that basal corticosterone pulsatility significantly impacts the vulnerability for developing post-traumatic stress disorder (PTSD). Rats that exhibited PTSD-phenotype were characterized by blunted basal corticosterone pulsatility amplitude and a blunted corticosterone response to a stressor. This study sought to identify the [...] Read more.
Previously, we found that basal corticosterone pulsatility significantly impacts the vulnerability for developing post-traumatic stress disorder (PTSD). Rats that exhibited PTSD-phenotype were characterized by blunted basal corticosterone pulsatility amplitude and a blunted corticosterone response to a stressor. This study sought to identify the mechanisms underlining both the loss of pulsatility and differences in downstream responses. Serial blood samples were collected manually via jugular vein cannula at 10-min intervals to evaluate suppression of corticosterone following methylprednisolone administration. The rats were exposed to predator scent stress (PSS) after 24 h, and behavioral responses were assessed 7 days post-exposure for retrospective classification into behavioral response groups. Brains were harvested for measurements of the glucocorticoid receptor, mineralocorticoid receptor, FK506-binding protein-51 and arginine vasopressin in specific brain regions to assess changes in hypothalamus–pituitary–adrenal axis (HPA) regulating factors. Methylprednisolone produced greater suppression of corticosterone in the PTSD-phenotype group. During the suppression, the PTSD-phenotype rats showed a significantly more pronounced pulsatile activity. In addition, the PTSD-phenotype group showed distinct changes in the ventral and dorsal CA1, dentate gyrus as well as in the paraventricular nucleus and supra-optic nucleus. These results demonstrate a pre-trauma vulnerability state that is characterized by an over-reactivity of the HPA and changes in its regulating factors. Full article
(This article belongs to the Special Issue Individual Variability in Animal Models of Psychopathologies)
►▼ Show Figures

Figure 1

18 pages, 3839 KiB  
Article
Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve
by Szu-Han Chen, Chia-Ching Wu, Sheng-Che Lin, Wan-Ling Tseng, Tzu-Chieh Huang, Anjali Yadav, Fu-I Lu, Ya-Hsin Liu, Shau-Ping Lin and Yuan-Yu Hsueh
Int. J. Mol. Sci. 2021, 22(9), 4746; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094746 - 29 Apr 2021
Cited by 12 | Viewed by 3177
Abstract
Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is [...] Read more.
Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future. Full article
(This article belongs to the Special Issue Individual Variability in Animal Models of Psychopathologies)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop