Examining the effect of environmental enrichment on the modulation of feeding and aggressive behaviours in mice and the associated expression of Bdnf transcript variants
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Date
2021-08-20
Authors
Aldhshan, Muhammad Shaaban
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Abstract
The home environment is a critical modulator of behaviour. Environmental enrichment (EE) is a laboratory housing protocol that employs complex sensory and social stimulations to enrich the cage environment of laboratory rodents. Prior studies suggested that EE elicits improvements in rodents' metabolic profile in addition to profound cognitive and behavioural outcomes, among which is reduced inter-male aggression. However, the underlying mechanism mediating the positive outcomes of EE remains poorly characterised. EE has been associated with altered brain-derived neurotrophic factor (Bdnf) gene expression. The Bdnf gene consists of multiple transcript variants, all of which encode for an identical protein. Remarkably, different Bdnf transcripts expression in different tissues influences different metabolic and behavioural functions. Therefore, we hypothesised that EE modifies the feeding and aggressive behaviours in mice via altering Bdnf gene expression in a transcript variant-specific and brain region-specific manner. To test this hypothesis, we employed behavioural and gene expression analyses to examine the influence of EE on feeding and aggressive behaviours and the associated expression of genes encoding neurotrophins in male C57BL/6 mice. In the first study, we showed, for the first time, that EE potentiates the feeding-suppressing effect of glucose in 8-hr fasted mice. Furthermore, intraperitoneal glucose injection promoted hypothalamic activation, as assessed by increased Fos expression. Moreover, glucose treatment significantly upregulated hypothalamic glial cell line-derived neurotrophic factor (Gdnf) mRNA levels while selectively downregulating Bdnf transcript variants levels in the hypothalamus and amygdala of the EE mice. In the second study, we showed that EE significantly reduced inter-male aggression in group-housed mice. This effect was associated with reduced activity of the aggression-linked corticolimbic circuits. Importantly, EE significantly reduced Bdnf transcript variant I (Bdnf I) expression in the prefrontal cortex, hypothalamus, hippocampus, and parietal cortex, whereas it significantly increased Bdnf I mRNA levels in the amygdala. Together, these data show that the effects of EE on feeding and aggressive behaviours are associated with brain region-specific alterations in neurotrophins gene expression. It is highly expected that the novel data reported in this thesis will further the current understanding of the role of the home environment in modulating behaviour at the brain level.
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Keywords
Environmental enrichment (EE), Feeding behaviour, Aggression, Brain-derived neurotrophic factor (BDNF), Glial cell line-derived neurotrophic factor (GDNF), Hypothalamus, Amygdala, Prefrontal cortex, Glucose, Leptin, Xenin, Gene-environment interactions, Enviromimetics, Intermale aggression, Laboratory rodents, Hippocampus, Corticolimbic system, Brain reward circuits, Food intake, Feeding pattern, Energy balance, Gene expression, qPCR, ELISA, GLUTs, Solute carrier (SLC), Serotonin (5-HT), GABA, Bdnf transcript variants, Bdnf I, Bdnf gene structure, Neuroendocrinology, Adibosity, Obesity, Brain