‘Super-Enrichment’ Reveals Dose-Dependent Therapeutic Effects of Environmental Stimulation in a Transgenic Mouse Model of Huntington's Disease

Mazarakis, Nektarios K.; Mo, Christina; Renoir, Thibault; Dellen, Anton van; Deacon, Robert M. J.; Blakemore, Colin; Hannan, Anthony J.

doi:10.3233/jhd-140118

Cited by 35 publications

(15 citation statements)

References 36 publications

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“…Chronic daily exposure to EE also results in decreased D1 receptor mRNA in the dorsal hippocampus (Ferrland et al 2014) and less D1 agonist-induced locomotion in EE-exposed rats compared to controls when D1 agonist was infused into the prefrontal cortex (Del Arco et al 2007). Finally, chronic EE results in less systemically administered D1 agonist-induced Fos in the striatum (Mazarakis et al 2014). If D1 receptors are downregulated in our chronic EE procedure, then adding SKF 81297 could have brought back the diminished D1 signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Of the findings yet reported, there are data supporting a role for altered dopamine function following EE. For example, several weeks of EE was associated with decreased dopamine D1 receptor expression (Del Arco et al 2007; Gill et al 2013; Ferland et al 2014), less D1 agonist-induced Fos protein expression (Mazarakis et al 2014) in mesolimbic brain regions, and less D1 receptor-induced locomotion when a D1 agonist was microinjected into the medial prefrontal cortex (Del Arco et al 2007). …”

Section: Introductionmentioning

confidence: 99%

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Effects of dopamine D1 and D2 receptor agonists on environmental enrichment attenuated sucrose cue reactivity in rats

et al. 2016

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Rationale Acute or chronic environmental enrichment (EE) reduces sucrose cue reactivity in rats. This effect may be mediated by dopamine receptors. Objectives We examined whether dopamine D1 or D2 receptor agonism could reverse the EE effect. We also examined whether any reversal effects would vary with the incubation of sucrose craving. Methods Following 10 days (2 h/day) of sucrose self-administration, rats experienced either 1 or 30 days of forced abstinence and either overnight (acute) or 29 day (chronic) EE. D1 (SKF 81297; 0, 0.3, or 1 mg/kg) or D2 (quinpirole; 0, 0.1, or 0.3 mg/kg) agonist was administered systemically immediately prior to a subsequent 2-h cue reactivity test the next day (n = 9–12 per group). Results Dose-dependent effects were limited to the day 1 test. High doses of the agonists increased day 1 acute EE cue reactivity to levels comparable to control animals. On the day 30 test, SKF 81297 increased cue reactivity in acute EE, chronic EE, and control rats. In contrast, quinpirole resulted in similar cue reactivity for control and enriched rats, more from a reduction in responding by controls vs. a recovery of responding by EE-experienced rats. Conclusions Both D1 and D2 receptors may be involved in the acute EE-mediated decrease in cue reactivity observed following 1 day of forced abstinence. In contrast, at 30 days of forced abstinence, D1 receptors may be critical in cue reactivity as SKF 81297 was effective at both restoring responding of enriched animals and potentiating responding of controls.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of dopamine D1 and D2 receptor agonists on environmental enrichment attenuated sucrose cue reactivity in rats

et al. 2016

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“…For example, apart from the novelty and the complex environment, EE can consist in putting food pellets at the bottom of the cage hidden with bedding, introducing different kinds of treats into toys, boxes or ice cubes, encouraging the animals to seek and work for food. This type of EE gives animals a certain control over their environment and essential resources [ 155 ]. However, not all types of EE are effective to improve the cognition and the welfare of the animals.…”

Section: What Is the Environmental Enrichmentparadigm?mentioning

confidence: 99%

Environmental Enrichment as a Positive Behavioral Intervention Across the Lifespan

Sampedro-Piquero

Begega

2017

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Background:In recent decades, the interest in behavioral interventions has been growing due to the higher prevalence of age-related cognitive impairments. Hence, behavioral interventions, such as cognitive stimulation and physical activity, and along with these, our lifestyle (education level, work position, frequency of cognitive and social activities) have shown important benefits during the cognitive impairment, dementia and even recovery after brain injury. This is due to the fact that this type of intervention and activities promote the formation of a cognitive and brain reserve that allows tolerating brain damage during a long period of time without the appearance of cognitive symptoms. With regard to this, animal models have proved very useful in providing information about the brain mechanisms involved in the development of these cognitive and brain reserves and how they interact with each other.Methods:We summarize several studies showing the positive effects of Environmental Enrichment (EE), understood as a housing condition in which animals benefit from the sensory, physical, cognitive and social stimulation provided, on brain and cognitive functions usually impaired during aging.Results:Most of studies have shown that EE is a successful protocol to improve cognitive functions and reduce anxiety-related behaviors across the lifespan, as well as in animal models of neurodegenerative diseases.Conclusion:Therefore, EE is a laboratory condition in which some aspects of an active lifestyle are reproduced.

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“…The observed beneficial effects of EE, in this case, may only be due to worsening of disease-related phenotypes in animals housed in deprived standard-housing conditions. Yet, the observed effects of EE remain relevant corroborated by reports employing higher levels of enrichment referred to 'super enrichment' (Mazarakis et al, 2014). Accounting for such considerations when interpreting findings from animal studies is vital to facilitate translation to clinical practice and define the type of environmental intervention necessary to achieve the functional benefits we aim for in patients.…”

Section: Discussionmentioning

confidence: 90%

Alpha‐synuclein at the nexus of genes and environment: the impact of environmental enrichment and stress on brain health and disease

Wassouf

Schulze‐Hentrich

2019

Journal of Neurochemistry

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Accumulation of alpha‐synuclein protein aggregates is the hallmark neuropathologic feature of synucleinopathies such as Parkinson’s disease. Rare point mutations and multiplications in SNCA, the gene encoding alpha‐synuclein, as well as other genetic alterations are linked to familial Parkinson’s disease cases with high penetrance and hence constitute major genetic risk factors for Parkinson’s disease. However, the preponderance of cases seems sporadic, most likely based on a complex interplay between genetic predispositions, aging processes and environmental influences. Deciphering the impact of these environmental factors and their interactions with the individual genetic background in humans is challenging and often requires large cohorts, complicated study designs, and longitudinal set‐ups. In contrast, rodent models offer an ideal system to study the influence of individual environmental aspects under controlled genetic background and standardized conditions. In this review, we highlight findings from studies examining effects of environmental enrichment mimicking stimulation of the brain by its physical and social surroundings as well as of environmental stressors on brain health in the context of Parkinson’s disease. We discuss possible internal molecular transducers of such environmental cues in Parkinson’s disease rodent models and emphasize their potential in developing novel avenues to much‐needed therapies for this still incurable disease. This article is part of the Special Issue “Synuclein”

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‘Super-Enrichment’ Reveals Dose-Dependent Therapeutic Effects of Environmental Stimulation in a Transgenic Mouse Model of Huntington's Disease

Cited by 35 publications

References 36 publications

Effects of dopamine D1 and D2 receptor agonists on environmental enrichment attenuated sucrose cue reactivity in rats

Effects of dopamine D1 and D2 receptor agonists on environmental enrichment attenuated sucrose cue reactivity in rats

Environmental Enrichment as a Positive Behavioral Intervention Across the Lifespan

Alpha‐synuclein at the nexus of genes and environment: the impact of environmental enrichment and stress on brain health and disease

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