Patricia Mesa-Gresa

Potential benefits and limitations of enriched environments and cognitive activity on age-related behavioural decline.

The main aim of this chapter is to review preclinical studies that have evaluated interventions which may aid in preventing or delaying age-related behavioural decline. Animal models of Environmental Enrichment (EE) are useful for evaluating the influence of cognitive, physical and social stimulation in mitigating cognitive decline at different ages. The EE paradigm has been proposed as a non-invasive treatment for alleviating age-related memory impairment and neurodegenerative diseases. While in this complex environment, rodents can be stimulated at different levels (physical, social, cognitive and sensorial), although a synergism between all these components is likely to play an important role. We will summarize available data relating to EE as a potential therapeutic strategy that slows down or counteracts age-related cognitive and behavioural changes. EE also alters physiological responses and induces neurobiological changes such as stimulation of neurogenesis and neural plasticity. At the behavioural level, EE improves learning and memory tasks and reduces anxiety. Several variables seem to influence the behavioural and cognitive benefits induced by EE, including the age at which animals are first exposed to EE, total period during which animals are submitted to EE, gender, the cognitive task evaluated, the drug administered and individual factors. Cognitive and physical stimulation of animals in enriched experimental environments may lead to a better understanding of factors that promote the formation of cognitive reserve (CR) and a healthier life in humans. In the present chapter we review the potential benefits of EE in aged rodents and in animal models of Alzheimer Disease (AD). Results obtained in preclinical models of EE may be relevant to future research into mental and neurodegenerative diseases, stress, aging and development of enviromimetics. Finally, we outline the main limitations of EE studies (variability between laboratories, difficulty of separating the different components of EE, gender of experimental subjects, individual differences in the response to EE), evaluating the potential benefits of enriched environments and the neurobiological mechanisms that underlie them. We conclude that there are experimental data which demonstrate the cognitive benefits of rearing rodents in enriched environments and discuss their implication for clarifying which variables contribute to the formation of the CR.

Environmental Enrichment Improves Novel Object Recognition and Enhances Agonistic Behavior in Male Mice

Environmental enrichment (EE) is an experimental paradigm in which rodents are housed in complex environments containing objects that provide stimulation, the effects of which are expected to improve the welfare of these subjects. EE has been shown to considerably improve learning and memory in rodents. However, knowledge about the effects of EE on social interaction is generally limited and rather controversial. Thus, our aim was to evaluate both novel object recognition and agonistic behavior in NMRI mice receiving EE, hypothesizing enhanced cognition and slightly enhanced agonistic interaction upon EE rearing. During a 4-week period half the mice (n = 16) were exposed to EE and the other half (n = 16) remained in a standard environment (SE). On PND 56-57, animals performed the object recognition test, in which recognition memory was measured using a discrimination index. The social interaction test consisted of an encounter between an experimental animal and a standard opponent. Results indicated that EE mice explored the new object for longer periods than SE animals (P < .05). During social encounters, EE mice devoted more time to sociability and agonistic behavior (P < .05) than their non-EE counterparts. In conclusion, EE has been shown to improve object recognition and increase agonistic behavior in adolescent/early adulthood mice. In the future we intend to extend this study on a longitudinal basis in order to assess in more depth the effect of EE and the consistency of the above-mentioned observations in NMRI mice.

Behavioral effects of combined environmental enrichment and chronic nicotine administration in male NMRI mice

Environmental enrichment (EE) is an experimental paradigm which provides sensory, social, physical and cognitive stimulation for rodents. Experimental evidence indicates that this type of housing induces different neurobiological and behavioral changes. However, few studies have evaluated the consequences of combined exposure to an enriched environment and nicotine administration during a critical period of development such as adolescence. Taking into account previous studies, it can be hypothesized that a chronic treatment with nicotine would modulate the effects of rearing animals in enriched environments. In the current study, our main aim was to evaluate the effects of EE and chronic nicotine administration on physiological parameters (weight, fluid intake and cotinine levels), motor activity, exploratory behavior, anxiety and learning in male NMRI mice. Half of the mice (n=32) were exposed to an enriched environment (EE) and the other half (n=32) were housed in standard environments (SE) with or without oral nicotine administration (100 μg/ml). After 3 weeks, mice were evaluated in a behavioral battery that included an elevated plus-maze, a hole board, an actimeter and an inhibitory avoidance task. Blood cotinine levels were measured in an additional group of 32 mice in order to confirm nicotine intake. Results indicated that mice reared in an enriched environment gained less body weight and displayed higher fluid intake than those maintained in a standard environment. EE reduced motor activity, exploratory behavior and anxiety, whereas it enhanced inhibitory avoidance learning. In relation to the effects of chronic nicotine treatment, the data reflected a lower increase in body weight and a reduced fluid intake in nicotine-treated mice. In the elevated plus-maze, nicotine induced a reduction of total arm entries and rearings. Cotinine levels were higher in mice that received oral nicotine than in the control group. We conclude that the EE paradigm applied in this study induces physiological and behavioral changes in NMRI mice. Chronic nicotine treatment diminished motor activity displayed by mice in the elevated plus-maze but did not have significant effects on inhibitory avoidance learning. Future studies should explore in greater depth the interaction between environmental factors and nicotine administration using longer periods of EE, a wider range of doses and/or other cholinergic agonists, acute drug administration, and sequential exposure to nicotine and EE.

Enriched environments for rodents and their interaction with nicotine administration.

An active lifestyle throughout the life cycle seems to delay cognitive aging and dementia and has also been evaluated as an intervention against addiction to cocaine and other drugs of abuse. In epidemiological studies with humans, it has proved difficult to separate the cognitive, social and physical components from other variables that influence lifestyle. Studies in animal models are useful for evaluating the impact of each of these factors and for uncovering the underlying mechanisms of the benefits of complex environments. Preclinical studies have employed the Environmental Enrichment paradigm (EE) which has been proposed as a preclinical model of positive life experiences in humans. EE has been associated with protective effects against addiction to some drugs, but few studies have been carried out in order to evaluate how its actions interact with nicotine addiction. In this context, the main aim of this review is to provide an analysis of the preclinical studies evaluating the interaction between exposure to enriched environments with the neurobiological and behavioral effects of nicotine administration. These studies will contribute to the development of future preventive and therapeutic applications of enriched environments and positive experiences for drug addiction in human beings, taking into account individual vulnerability. They also may shed light on new approaches to the treatment of nicotine addiction, as interventions based in physical exercise in interaction with other environmental variables.

Behavioral effects of different enriched environments in mice treated with the cholinergic agonist PNU-282987.

Environmental enrichment is an experimental model in which rodents are housed in complex environments that favor lower levels of anxiety-like behavior. PNU-282987 (PNU) is a α7 nicotinic acetylcholine receptor agonist with beneficial effects on learning though its effects on anxiety are unclear. Our main aim was to carry out a study of its effects in NMRI (n=96) mice reared in different environments: environmental enrichment (EE), Marlau™ cages (MC) and standard environment (SE). After a 4-month period, mice received acute treatment of PNU (2.5, 5 and 10mg/kg) and were evaluated in the elevated plus-maze (EPM) and hole-board (HB). In the EPM, both EE and MC reared mice showed an increase in percentage of entries into open arms while those from EE group differed from SE in time spent on open arms. Mice treated with 2.5 and 10 mg/kg of PNU devoted less time to rearing into open arms. In the HB task, MC mice displayed higher exploratory activity reflected in more head-dips (HD) during the first minute than EE and SE, whereas EE displayed low exploration levels reflected in total HD (5 min). Further research is needed in order to clarify the behavioral effects of this nicotinic agonist in interaction with different environmental conditions. This article is part of a Special Issue entitled: insert SI title.

Nicotina y modelos animales: ¿qué nos aporta el paradigma de enriquecimiento ambiental?

The Environmental Enrichment (EE) paradigm is a housing condition which aims is to provide physical, cognitive and sensorial stimulation to rodents. Animals are housed in larger cages containing inanimate objects such as tunnels, toys and running wheels. The main aim of the current work is to tackle the arguments which suggest that EE may diminish vulnerability to developing addiction to nicotine and other drugs of abuse and to review recent experimental studies performed in relation to this subject. We discuss the major changes induced by EE at physical, neurobiological and behavioral levels and review the results of recent studies which indicate that EE promotes both neurochemical (potentiation of the increase in dopamine release induced by nicotine in the brain cortex) and behavioral changes (increased ability to discriminate the presence of reward and decreased impulsivity), thus supporting the hypothesis put forward. In light of these results, EE can be proposed as a model for the study of vulnerability to addiction to different drugs of abuse, including cocaine and nicotine, though further studies are needed in order to establish the neurobiological implications of the effects of exposure to enriched environments and their possible relationship with changes in brain reward systems.

Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions

The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions.

Cuidado de pacientes oncológicos: una revisión sobre el impacto de la situación de estrés crónico y su relación con la personalidad del cuidador y otras variables moduladoras

Objective: The prevalence of long-term diseases such as cancer has increased in recent years. In this context, our aim will be to analyze the main consequences resulting from exposure to a chronic stress situation, such as the care of an oncologic patient. The effects of this situation on the psychosocial health and cognitive function of informal caregivers and their relationship with possible modulating variables will be revised. Method: A bibliographic review was performed in PubMed and PsycINFO databases about the consequences related to the caregiving of patients with chronic diseases. Results: Several studies suggest that the condition of caregiver of cancer patients could be considered as an and stressful situation. It has consequences on caregiver’s physical and psychosocial health, and can induce a decrease of cognitive functioning, although these changes may be modulated by different variables. Conclusion: These data suggest the need of implementing intervention programs in order to mitigate the deleterious consequences of the caregiving situation.