Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat

Abstract

Further examination of the molecular regulators of long-term calorie restriction (CR), reported to have an anxiolytic effect, may highlight novel therapeutic targets for anxiety disorders. Here, adult male Hooded Wistar rats were exposed to a 25% CR whilst anxiety-like behaviour was assessed at 6-, 12-, and 18-months of age via the elevated plus maze, open field, and acoustic startle tests. Next-generation sequencing was then used to measure transcriptome-wide gene expression in the hypothalamus, amygdala, pituitary, and adrenal glands. Results showed an anxiolytic behavioural profile across early, middle, and late adulthood by CR, with the strongest effects noted at 6-months. Transcriptomic analysis by seven attribute weighting algorithms, including Info Gain Ratio, Rule, Chi Squared, Gini Index, Uncertainty, Relief, and Info Gain, led to the development of a signature of long-term CR, independent of region. Complement C1q A chain (C1qa), an extracellular protein, expression was significantly decreased by CR in most regions examined. Furthermore, text mining highlighted the positive involvement of C1qa in anxiety, depression, neurodegeneration, stress, and ageing, collectively identifying a suitable biomarker candidate for CR. Overall, the current study identified anxiety-related phenotypic changes and a novel transcriptome signature of long-term CR, indicating potential therapeutic targets for anxiety, depression, and neurodegeneration.

Gut Microbiota and Behavioural Issues in Production, Performance, and Companion Animals: A Systematic Review

“…While these types of studies are in their early stages, future multidisciplinary studies could include careful measurement of behavioural changes using ethograms to determine the impact of feed additives on stress responses, aggressive behaviour, and fearfulness. Inclusion of specific spices in the diet, such as Curcuma longa L., Piper nigrum L., Capsicum anuum L., and Zingiber officinale L., can increase serotonin 5-HT1A receptors in the hippocampus and enhance serotoninergic system regulation and neurotrophic factor expression in the hippocampus and prefrontal cortex [97,98]. The hippocampus and prefrontal cortex are the main areas of the brain affected by most mood disorders such as anxiety [98,99].…”

“…Inclusion of specific spices in the diet, such as Curcuma longa L., Piper nigrum L., Capsicum anuum L., and Zingiber officinale L., can increase serotonin 5-HT1A receptors in the hippocampus and enhance serotoninergic system regulation and neurotrophic factor expression in the hippocampus and prefrontal cortex [97,98]. The hippocampus and prefrontal cortex are the main areas of the brain affected by most mood disorders such as anxiety [98,99].…”

“…While there is great potential for additives such as these to play a permanent role in the health and performance of humans and animals alike, further evidence-based studies (such as doubleblind placebo-controlled clinical trials) are required before they can be recommended in any treatment regime. Calorie restriction in the diet is another potential beneficial strategy to decrease anxiety and depression [98].…”

Pattern discovery of long non‐coding RNAs associated with the herbal treatments in breast and prostate cancers

“…Furthermore, the top GO analysis indicated that the genes of lncRNA FUT8-AS1 were mainly involved in the cellular carbohydrate biosynthetic process, leucinezipper, carbohydrate biosynthetic process, protein dimerization activity, and glucose metabolic process. FUT8-AS1 is associated with mRNAs involved in the most frequently reported metabolic alterations in cancer patients, including resting energy expenditure linked with increased metabolism of carbohydrate, lipid, and protein metabolism, which are all typical of cancer cells [47,48]. Association of lncRNA FUT8-AS1 to these mRNAs suggests that this lncRNA can serve as a novel biomarker or therapeutic target candidate for patients with BC or PC.…”

Rasd2 Mediates Acute Fasting-Induced Antidepressant-Like Effects via Dopamine D2 Receptor Activation in Ovariectomized Mice

“…Calorie restriction has been shown to extend the life span of several species over the past few decades ( Fontana and Partridge, 2015 ) and has positive effects on neurological diseases, including Alzheimer’s disease and Parkinson’s disease ( Zhang et al, 2021b ; Ezzati and Pak, 2023 ; Govic et al, 2022 ). In our previous studies, mice treated with 9-hour fasting significantly shortened the immobility time of the forced swimming test (FST), whereas mice fasted for 3 hours and 18 hours had no significant changes ( Li et al, 2014 ).…”