Topic: cognitive deficits

In 2019, a report by world stroke organisation (WSO) states that there are 12.2 million new cases of ischaemic stroke per year with 6.5 million people dying annually. Stroke is the third nationally and second globally highest in terms of mortality and third highest worldwide in terms of Disability Adjusted Life Years (DALYs). Chronic ischaemia, constituting 62% of all stroke cases; and cognitive impairment are reported to be 50% associated in patients younger than 50 years, foisting a huge burden on their families. Post stroke cognitive impairment (PSCI) includes the damages caused to the cogn

Increasing evidence have highlighted significant sex-related differences in animal physiology and behavior, both in health and disease. Despite that, most neuroscience research involving animal models is still conducted using males only. Estrogen (E2) is known to have a protective role in females, mainly by preventing inflammation, however, when hormone levels decline, females become more prone than males to metabolic, cardiovascular and psychiatric diseases. Thanks to our established conditional knockout mouse model (Npy1rrfb mice), in which the gene encoding for the main NPY receptor Y1 is s

Cognitive deficits and negative symptoms associated with schizophrenia are poorly managed by current antipsychotics. In order to develop effective treatments, refining animal models of schizophrenia is essential. To address its multifactorial etiology, we developed a new 3-hit mouse model. This model was mostly concealing the glutamatergic deficit hypothesis of the pathology (underlying cognitive and negative deficits). Thus, a genetic susceptibility (serine racemase deletion) was associated to environmental stress (24h maternal separation at 9-day of age) and pharmacological treatment (phency

Maternal obesity during pregnancy is a significant global health concern, impacting the metabolic, cardiovascular, and neurological health of the offspring, the latter being a research topic that has become of great interest. Our study investigates their effects on cognition, focusing on the hippocampus, a region vulnerable to prenatal insults. While maternal high-fat diet (mHFD) has been linked to cognitive deficits and hippocampal changes, its impact on synaptic transmission remains unexplored.Our focus was to understand how this adverse prenatal environment influences memory processes and w

Introduction: Maternal immune activation (mIA) is a risk factor for schizophrenia. It is hypothesised that mIA-induced fetal neuroinflammation alters neurodevelopment and predisposes offspring to neuropathology. Using our validated mIA model, exposing pregnant rats to the viral mimetic poly(I:C), we have shown that adult offspring exhibit cognitive deficits comparable to those in schizophrenia, and have genomic methylation changes enriched for oligodendrocyte genes.Aims: Examine the relationship between mIA and altered oligodendrocyte development and how these correspond to the onset of adult

The brain, particularly the hippocampus, is sensitive to age-related cellular changes, leading to cognitive deficits. Recent work by our laboratory has demonstrated that autophagy, a catabolic lysosomal-dependant process, is reduced in aged hippocampal neurons, and that restoring autophagy levels is sufficient to improve age-related memory impairment. Nonetheless, the regulatory mechanisms involved in neuronal autophagy decline during aging remain largely unknown. Exploring this question, we found that WD repeat domain phosphoinositide-interacting protein 2 (WIPI2), an important driver of auto

Parkinson's disease (PD) is a complex pathology presenting with motor symptoms coupled with a variety of non-motor symptoms originating in the central nervous system or the periphery, resulting in a complex multisystem disease. The development of therapeutic approaches to slow or stop disease progression remains the greatest unmet therapeutic need for PD. The immune system plays a pivotal role in the central and peripheral pathology of PD, reacting to misfolded α‐synuclein with neuroinflammation and dysregulation of peripheral immune responses. Here, we tested the neuroprotective properties of

To investigate gene x environment interactions in a mouse model of cognitive deficits, we examined the impact of mild stress in mice genetically modified to express deficient levels of glutamate dehydrogenase 1 (GDH). GDH (gene name: Glud1) plays a central role in glutamate metabolism and is downregulated in the hippocampus of patients with schizophrenia. Mice with a full deletion of Glud1 in CNS (C-Glud1-/- mice) previously showed abnormally high glutamate levels and a wide range of behavioral deficits. Here, we exposed heterozygous C-Glud1+/- mice and their C-Cre+ controls to mild stress in

Schizophrenia (SCZ) is a frequent psychosis related to combination between genetic and environmental factors. To advance current treatments, it is important to improve animal models by considering its multifactorial etiology. Our study aimed to characterize an innovative 2-hit mouse model combining the deletion of serine racemase (genetic factor) associated with a maternal separation for 24h at post-natal day 9 (early stressing environmental factor), which both have been previously suggested to possibly drive SCZ-like symptoms. The face facility of this 2-hit model was assessed through behavio

Microglia are keen responders in numerous neurodevelopmental and neurodegenerative conditions, including in Multiple Sclerosis (MS). While previous studies hinted about microglia involvement in synaptic elimination, their correlation with the appearance of cognitive deficits in MS remains unclear. Here, we focused on understanding the impact of microglia in MS synapse pruning in the cognitive-related region, the hippocampus, using postmortem tissue of MS patients. Hippocampal samples were obtained from the Netherlands Brain Bank, including non-demented control (NDC) and MS donors that were mat