Biology subjects

D'Hooge, R.

Publications and source records attributed to D'Hooge, R..

3 recordsLinked to original sources

bioRxiv2021

Scopolamine blocks context-dependent reinstatement of fear responses in rats

Return of fear poses a problem for extinction-based therapies of clinical anxiety. Experimental research has discovered several pathways to return of fear, one of which is known as reinstatement. Here, we evaluated in rats the potential of scopolamine, a non-selective muscarinic receptor antagonist that is also safe for use in humans, to prevent the reinstatement of extinguished fear. We conducted three experiments with a total sample of 96 female rats. All rats went through a fear acquisition session (tone-shock pairings, CS-US), followed by two extinction sessions (CS only) and a post-extinction fear memory test. Twenty-four hours later, rats were placed in the same or a different context from extinction and received two unsignaled foot shock (US) presentations. On the following day, CS-evoked freezing returned when the reinstating USs had occurred in the same context compared to a different context (context-dependent reinstatement, Experiment 1). Systemic administration of scopolamine before or after the reinstating USs blocked the return of CS-evoked freezing on the following day (Experiments 2 and 3). Our findings suggest that administering scopolamine around the time of an aversive experience could prevent relapse of extinguished fears in humans.

neuroscience↗

bioRxiv2019

Social isolation impacts late-life socio-cognitive decline in APP/PS1 mice

In this study the effects of social isolation (SI) were investigated in APP/PS1 mice. It was found that SI during adolescence has an impact on anxiogenic behaviour, such that isolated animals tend to explore a threatening environment less than non-isolated animals as assessed with the EPM test, and that this holds for both AD and non-AD mice. While no evidence was found for any differences in short-term memory as assessed by the Y-maze, long-term memory seemed to be affected in a context-dependent manner. Object memory as assessed with the NOR test was affected in APP/PS1 mice compared to WT mice, but this deficit was not induced or influenced by SI. When it comes to social recognition memory however, we found that SI exacerbated the social memory deficit in AD mice, and even induced a deficit in WTs. Associative fear memory as assessed with the PA test suggested that WTs perform better when group housed, and APP/PS1 mice better when socially isolated. The link between isolation and AD, or cognition in general, may be more complex than initially thought. The effect of isolation may not be the same for AD versus non-AD subjects.

neuroscience↗

bioRxiv2019

Isolation housing exacerbates Alzheimer’s Disease phenotype in aged APP KI mice

In January 2018, Britain was the first in the world to adopt a Minister of Loneliness. This illustrates the changing view on loneliness: being lonely is not just a feeling of a lack of companionship, but also a serious health problem. For example, we know that loneliness is as bad as smoking 15 cigarettes a day. Moreover, research has shown that lonely people express higher levels of cortical amyloid. Amyloid burden is an important marker of Alzheimers Disease (AD), a chronic neurodegenerative disease and the main cause of dementia worldwide. Together with other findings a link between loneliness, (perceived) social isolation and AD is now undeniable, but it is hard to tell from human studies whether it is the cause or the effect of AD. We need standardized animal studies to answer this question.\n\nIn an effort to study how social isolation and AD interact, we used APP KI mice bearing human transgenes known to cause AD, and isolated part of the mice in order to mimic loneliness in late-life while part of them remained group-housed. We next looked at the effects of isolation on the behaviour and symptomatology typically present in AD patients to tap cognition.\n\nOur study reveals mixed results. Results indicate that at before isolation, at the age of 16 and 24 months, APPNL/NL and APPNL-G-F/NL-G-F mice do not differ to a significant extent on both the behavioural level. The APPNL-G-F/NL-G-F differentiated slightly worse between the conditioned context and a new context compared to the APPNL/NL mice. However, the difference appeared to be more pronounced after a period of social isolation. Social isolation had distinct effects on the AD-related anxiogenic and dementia-like phenotype. Spatial learning in the MWM task revealed distinct differences between our two models. After isolation APPNL-G-F/NL-G-F mice used less spatial search strategies, compared to control mice, thus reflecting perseveration and less behavioural flexibility due to the isolation period.

neuroscience↗