Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice

Benfato, Izabelle Dias; Quintanilha, Ana Carolina Silvares; Henrique, Jéssica Salles; Souza, Melyssa Alves; Rosário, Bárbara dos Anjos; Filho, José Ivo Araújo Beserra; Santos, Ronaldo Oliveira dos; Ribeiro, Alessandra Mussi; Sueur-Maluf, Luciana Le; Oliveira, Camila Aparecida Machado de

doi:10.1016/j.bbr.2021.113630

Cited by 18 publications

(9 citation statements)

References 65 publications

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“…The effect of SI on the basal activity of the HPA axis is controversial (Serra et al, 2005). The type, number, timing, and order of the behavioral tests conducted in previous studies differed from those used in this study (Benfato et al, 2022;Chang et al, 2015;Donovan et al, 2021;Guo et al, 2021), which might have contributed to these differences. Therefore, the protective effect of betaine treatment on the abnormal behavior and microglial function of SI mice might not be due to altered activity of the HPA axis.…”

Section: Discussionmentioning

confidence: 73%

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice

Shi

Sun³

et al. 2023

Phytotherapy Research

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Chronic social isolation (SI) stress, which became more prevalent during the COVID‐19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti‐inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three‐week‐old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline‐treated GH, normal saline‐treated SI, and betaine‐treated SI groups in the sixth week. The cognitive and depression‐like behavior was determined in the eighth week. We found that long‐term betaine administration improved cognitive behavior in SI mice but failed to prevent depression‐like behavior. Moreover, long‐term betaine administration inhibited hippocampal microglia over‐activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic–pituitary–adrenal axis. Collectively, our findings reveal that betaine can improve SI‐induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.

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Section: Discussionmentioning

confidence: 73%

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice

Shi

Sun³

et al. 2023

Phytotherapy Research

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“…2). Environmental and social isolation, as triggered by single housing, represent behavioural/environmental stress‐like allostatic stimuli (Lee et al., 2020, 2021) that can trigger a transient reduction of food intake (Benfato et al., 2022; Takatsu‐Coleman et al., 2013). Interestingly, we observed that 6‐OHDA PVT mice were less sensitive to single housing‐induced hypophagia compared to Sham PVT mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress‐related contexts

Dumont

Castel

et al. 2022

The Journal of Physiology

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The regulation of food intake and energy balance relies on the dynamic integration of exteroceptive and interoceptive signals monitoring nutritional, metabolic, cognitive, and emotional states. The paraventricular thalamus (PVT) is a central hub that, by integrating sensory, metabolic, and emotional states, may contribute to the regulation of feeding and homeostatic/allostatic processes. However, the underlying PVT circuits still remain elusive. Here, we aimed at unravelling the role of catecholaminergic (CA) inputs to the PVT in scaling feeding and metabolic efficiency. First, using region‐specific retrograde disruption of CA projections, we show that PVT CA inputs mainly arise from the hindbrain, notably the locus coeruleus (LC) and the nucleus tractus solitarius. Second, taking advantage of integrative calorimetric measurements of metabolic efficiency, we reveal that CA inputs to the PVT scale adaptive feeding and metabolic responses in environmental, behavioural, physiological, and metabolic stress‐like contexts. Third, we show that hindbrainTH→PVT inputs contribute to modulating the activity of PVT as well as lateral and dorsomedial hypothalamic neurons. In conclusion, the present study, by assessing the key role of CA inputs to the PVT in scaling homeostatic/allostatic regulations of feeding patterns, reveals the integrative and converging hindbrainTH→PVT paths that contribute to whole‐body metabolic adaptations in stress‐like contexts. Key points The paraventricular thalamus (PVT) is known to receive projections from the hindbrain. Here, we confirm and further extend current knowledge on the existence of hindbrainTH→PVT catecholaminergic inputs, notably from the locus coeruleus and the nucleus tractus solitarius, with the nucleus tractus solitarius representing the main source. Disruption of hindbrainTH→PVT inputs contributes to the modulation of PVT neuron activity. HindbrainTH→PVT inputs scale feeding strategies in environmental, behavioural, physiological, and metabolic stress‐like contexts. HindbrainTH→PVT inputs participate in regulating metabolic efficiency and nutrient partitioning in stress‐like contexts. HindbrainTH→PVT inputs, directly and/or indirectly, contribute to modulating the downstream activity of lateral and dorsomedial hypothalamic neurons.

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“…In order to study the role of PVT catecholaminergic inputs in the regulation of feeding patterns, 6-OHDA PVT and Sham PVT mice were single-housed ( Figure 2B ). Environmental and social isolation, as triggered by single housing, represent behavioral/environmental stress-like allostatic stimuli (Lee et al ., 2020, 2021) which can trigger a transient reduction of food intake (Takatsu-Coleman et al ., 2013; Benfato et al ., 2022). Interestingly, we observed that 6-OHDA PVT mice were less sensitive to single housing-induced hypophagia compared to Sham PVT mice ( Figure 2C ).…”

Section: Resultsmentioning

confidence: 99%

Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress-related contexts

Dumont

Castel

et al. 2022

Preprint

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Aim: The regulation of food intake and energy balance relies on the integration of exteroceptive and interoceptive signals monitoring nutritional, metabolic and emotional states. This study aims at unraveling the role of catecholaminergic (CA) inputs to the paraventricular thalamus (PVT) in scaling feeding and metabolic efficiency. Methods: To tackle this question, a region-specific retrograde disruption of PVT CA inputs was performed. Behavioral tests and in vivo calorimetric technologies were mobilized to study the adaptive strategies underlying feeding, metabolic efficiency and nutrient partitioning. Moreover, immunofluorescence investigations were conducted to identify the sources of TH-neurons projecting to the PVT and to reveal the molecular pattern of neuronal activation (cFos) in the PVT as well as in homeostasis-related regions of the hypothalamus. Results: First, we show that PVT CA inputs mainly arise from the hindbrain, notably the locus coeruleus (LC) and the nucleus tractus solitarius (NTS). Second, we reveal that PVT CA inputs contribute to feeding strategies and metabolic efficiency in environmental, behavioral, physiological and metabolic stress-like contexts. Third, we show that PVT CA inputs contribute in modulating the activity of PVT as well as lateral (LH) and dorsomedial (DMH) hypothalamic neurons. Conclusion: This study, by assessing the key role of PVT CA inputs in scaling homeostatic and allostatic regulations of feeding patterns, reveals the integrative and converging hindbrain→PVT paths that contribute to whole-body metabolic adaptations in stress-like contexts.

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Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice

Cited by 18 publications

References 65 publications

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice

Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress‐related contexts

Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress-related contexts

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