Biology subjects

Bonapersona, V.

Publications and source records attributed to Bonapersona, V..

6 recordsLinked to original sources

bioRxiv2022

Structural changes after early life adversity in rodents: a systematic review with meta-analysis

Early life adversity (ELA) is a well-documented risk factor for psychiatric illnesses in humans. This risk may, in part, be conferred by structural changes induced by ELA, lasting into adulthood. We here review the evidence for such lasting structural changes in rodent models for ELA involving altered maternal care during the first two postnatal weeks. In total, we extracted data from 64 studies reporting on 260 comparisons in adult rats or mice which experienced ELA or control treatment. Most of the observations concerned structural changes in the hippocampus of adult male rats earlier exposed to maternal separation. A 3-level meta-analysis revealed that ELA reduced hippocampal volume and the number of dendritic branches as well as dendritic length of principal hippocampal cells. No differences were observed across the hippocampal subfields. In terms of adult neurogenesis in the dentate subgranular zone, both staining for BrdU and the early neuronal marker DCX were significantly reduced, while the general proliferation marker Ki67 remained unchanged. The neuronal growth factor BDNF did not show significant changes, although the unexplained heterogeneity was moderate. Generally, the effect of ELA compared to control on structural markers was not affected by additional stressors experienced in life. Overall, the data available support the notion that ELA, at least in the hippocampus of male rats, lastingly reduces volume, hampers dendritic growth and suppresses adult neurogenesis.

neuroscience↗

bioRxiv2021

Effects of early life adversity on immediate early gene expression: systematic review and 3-level meta-analysis of rodent studies

Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced multiple negative life events. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naive, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.

neuroscience↗

bioRxiv2021

Pipeline for 4D whole-brain microscopy preprocessing and analysis.

Acute stress leads to sequential activation of functional brain networks. The challenge is to get insight in whole brain activity at multiple scales, beyond the level of (networks of) nuclei. We developed a novel pre-processing and analytical pipeline to chart whole-brain immediate early genes expression - as proxy for cellular activity - after a single stressful foot-shock in 4 dimensions; that is, from functional networks up to 3D single-cell resolution, and over time. The pipeline is available as R-package. Most brain areas (96%) showed increased numbers of c-fos+ cells after foot-shock, yet hypothalamic areas stood out as being most active and prompt in their activation, followed by amygdalar, prefrontal, hippocampal and finally thalamic areas. At the cellular level, c-fos+ density clearly shifted over time across subareas, as illustrated for the basolateral amygdala. Moreover, some brain areas showed increased numbers of c-fos+ cells, while others dramatically increased c-fos intensity in just a subset of cells; this strategy changed after foot-shock in half of the brain areas. All single-cell data can be visualized for each of the 90 brain areas examined through our interactive web-portal.

neuroscience↗

bioRxiv2019

RePAIR: a power solution to animal experimentation

Low statistical power challenges the reliability of animal research; yet, increasing sample sizes to the required level raises important ethical and practical issues. We present an alternative solution, RePAIR, which capitalizes on the observation that control groups in general are expected to be similar to each other. As shown in a simulation study, including information of previous control experiments in the statistical analysis using RePAIR reduced the required sample size by 49% or increased power up to 100%. We validated the potential of RePAIR in a unique dataset based on 7 independent experiments across the world, studying cognitive effects of early life adversity in mice. RePAIR comes with an open-source web-based tool and can be widely used to largely improve quality of animal experimentation. One Sentence SummaryPrior studies information can reduce use of animals or increase statistical power, improving animal research reliability

animal behavior and cognition↗

bioRxiv2019

The behavioral phenotype of early life adversity: a 3-level meta-analysis of rodent studies

1BackgroundAltered cognitive performance has been suggested as an intermediate phenotype mediating the effects of early life adversity (ELA) on later-life development of mental disorders, e.g. depression. Whereas most human studies are limited to correlational conclusions, rodent studies can prospectively investigate how ELA alters cognitive performance in a number of domains. Despite the vast volume of reports, no consensus has yet been reached on the i) behavioral domains being affected by ELA and ii) the extent of these effects.\n\nMethodsTo test how ELA (here: aberrant maternal care) affects specific behavioral domains, we used a 3-level mixed-effect meta-analysis, a flexible model that accounts for the dependency of observations. We thoroughly explored heterogeneity with MetaForest, a machine-learning data-driven analysis never applied before in preclinical literature. We validated the robustness of our findings with substantial sensitivity analyses and bias assessments.\n\nResultsOur results, based on >400 independent experiments, yielded >700 comparisons, involving ~8600 animals. Especially in males, ELA promotes memory formation during stressful learning but impairs non-stressful learning. Furthermore, ELA increases anxiety and decreases social behavior. The ELA phenotype was strongest when i) combined with other negative experiences (\"hits\"); ii) in rats; iii) in ELA models of ~10days duration.\n\nConclusionProspective and well-controlled animal studies demonstrate that ELA durably and differentially impacts distinct behavioral domains. All data is now easily accessible with MaBapp (https://osf.io/ra947/), which allows researchers to run tailor-made meta-analyses on the topic, thereby revealing the optimal choice of experimental protocols and study power.

neuroscience↗

bioRxiv2018

Effects of early life stress on biochemical indicators of the dopaminergic system: a 3 level meta-analysis of rodent studies

1. Introduction 1. Introduction 2. Materials and Methods 3. Results 4. Discussion 6 REFERENCES During the perinatal period, the brain matures and is rapidly wired(Semple et al. 2013), rendering it particularly vulnerable to negative life experiences that might lastingly impact brain function and behavior(Levine 2005). This may contribute to the well-established observation that exposure to adverse conditions during childhood is a major risk factor for the later development of psychopathologies(Teicher et al. 2016), including schizophrenia and substance abuse(Agid et al. 1999; Enoch 2011; Dube et al. 2003; Scheller-Gilkey et al. 2002).\n\nPrevailing evidence highlights that the dopamine (DA) system may ...

neuroscience↗