Abstract
Several interventions have been shown to counteract the effects of stress that may be related to improved neuroplasticity and neuronal activation. In this sense, environmental enrichment (ENR) protects against acute stress and increases neuroplasticity. It has been suggested that the use of patterned auditory stimuli (PAS) may be beneficial in increasing the effectiveness of ENR on disorders related to stress, such as depression and anxiety. Examples of PAS are classical music compositions that have interesting effects at both clinical and preclinical levels. Thus, we analyzed the effects of the exposure to PAS, represented in this study by Mozart's compositions, during ENR housing for 35 days in adult male Balb/C mice to evaluate depression-associated behavior using the forced-swim test (FST) paradigm with an additional short exposure to PAS. We found that the ENR mice that were exposed to PAS during both housing and behavioral task (ENR + PAS/FST + PAS) show decreased immobility and the number of despair episodes within a higher latency to show the first bout of immobility. Additionally, we found increased neuronal activation evaluated by the identification of activity-regulated cytoskeleton-associated protein- (Arc-) labeled cells in the prefrontal cortex (PFC) in mice exposed to PAS during housing and in the absence or presence of PAS during FST. Moreover, we found increased neuronal activation in the auditory cortex (AuCx) of mice exposed to PAS during FST. Our study suggests that the exposure to PAS during an emotional challenge decreases despair-like behavior in rodents that were previously housed in an enriched environment in combination with auditory stimuli. Thus, our data indicate that the role of the exposure to PAS as an intervention or in combination with positive environment to aid in treating neuropsychiatric disorders is worth pursuing.
Highlights
Environmental enrichment (ENR) has been widely described as strong social, physical, and cognitive stimuli that are able to induce beneficial effects in different types of preclinical models of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases (i.e., [1, 2]) and in preclinical models of psychiatric disorders, such as depression and anxiety (i.e., [3,4,5])
To know whether adult male Balb/C mice were able to perceive the auditory stimuli used in the present study, animals were exposed to patterned auditory stimuli (PAS) to further quantify associated protein- (Arc-)positive cells in the auditory cortex (AuCx) (Figure 1(a))
Quantification of activity-regulated cytoskeletonassociated protein (Arc)-positive cells in the AuCx (Figure 1(b)) revealed that mice exposed to PAS showed a significant increase (169%) in the number of Arcpositive cells compared to the control group (p = 0 049) (Figure 1(c))
Summary
Environmental enrichment (ENR) has been widely described as strong social, physical, and cognitive stimuli that are able to induce beneficial effects in different types of preclinical models of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases (i.e., [1, 2]) and in preclinical models of psychiatric disorders, such as depression and anxiety (i.e., [3,4,5]). The mechanism by which ENR induces beneficial effects against depression- and anxiety-like behaviors in preclinical models is, in part, related to neuroplasticity-associated changes, such as the generation of new neurons in the dentate gyrus (i.e., [1, 2]). The presence of greater numbers of new neurons in the dentate gyrus can help to buffer the effects of stress (i.e., [3,4,5,6,7,8]). The protective effects of ENR have been related to increased levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glia-derived neurotrophic factor (GDNF), which are implicated in neuroplasticity and neuronal activation processes [7,8,9,10,11,12]. Some reports have suggested the involvement of signaling molecules, such as mitogen-activated protein kinases (MAPK) and protein kinase B, known as Akt, in the beneficial effects of ENR (i.e., [12])
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