Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Dietary Treatment
2.3. Behavioural Testing
2.3.1. Elevated Plus Maze
2.3.2. Open Field Test
2.3.3. Acoustic Startle
2.4. RNA Preparation and Sequencing
2.5. Data and Statistical Analysis of Body Weight and Behavioural Data
2.6. Transcriptomic Data Analysis
2.7. Signature Discovery by Attribute Weighting (Feature Selection) Models
2.8. Text Mining and Integrative Network Analysis of Expressed Genes with Behaviour
3. Results
3.1. Body Weight
3.2. Elevated Plus Maze
3.3. Open Field
3.4. Acoustic Startle
3.5. Tissue-Based Response to Long-Term CR: Genes with Significant Differential Expression in Each Region of Interest
3.6. Tissue-Independent Transcriptomic Signature of Long-Term CR: Application of Attribute Weighting Analysis of Gene Expression
3.7. Text Mining-Based Network Analysis Links Long-Term CR Transcriptomic Signature with Behaviour (Anxiety, Depression, Cognition), Ageing and HPA-Axis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Category | Sub-Category | Number |
---|---|---|
Entities | Proteins | 144,002 |
Cell Objects, such as extracellular organelle | 632 | |
Cell process, including ageing | 14,153 | |
Cells, including cell lines information | 4297 | |
Clinical parameters, including energy consumption, energy expenditure, energy intake, and fertility | 5452 | |
Complexes, such as fatty acid beta-oxidation multienzyme | 994 | |
Diseases, including depression and anxiety | 23,016 | |
Pathogens | 607 | |
Small molecules, including drugs | 1,057,758 | |
Treatments, including stress | 88 | |
Tissue, such as hypothalamus | 3908 | |
Functional Classes, such as Fe transporter | 5570 | |
Genetic Variants | 168,360 | |
Virus | 25,323 | |
Tissues, such as lung mucosa | 588 | |
Total Entities | 1,454,748 | |
Relations | Binding relations | 1,176,779 |
Biomarker relations | 155,684 | |
Cell expression relations | 1,544,338 | |
Chemical reaction relations | 64,482 | |
Clinical trial relations | 133,031 | |
Direct regulation relations | 798,934 | |
Expression relations | 1,061,638 | |
Functional associations | 2,120,740 | |
Genetic change relations | 481,568 | |
Molsynthesis | 185,956 | |
Moltransport | 295,541 | |
Promoter binding | 52,413 | |
Protein modification relations | 85,659 | |
Quantitative change relations | 533,337 | |
Regulation relations | 6,644,356 | |
State change relations | 174,659 | |
MicroRNA effects | 71,649 | |
Total Relations | 15,580,764 |
Gene Name | Ensembl Identifier | Fold Change | |||
---|---|---|---|---|---|
Hypothalamus | Amygdala | Pituitary | Adrenal Glands | ||
LOC687780 | 20982 | −1.83 *** | −1.81 ** | −1.83 *** | −2.1 *** |
AC134224.2 | 62155 | 1.44 ** | 3.66 *** | 2.88 *** | 1.46 ** |
AABR07044397.1 | 50998 | 3.31 * | 7.47 ** | 5.97 *** | 285.24 *** |
LOC300308_1 | 48230 | 1.72 *** | 4.44 *** | 1.8 ** | 1.64 * |
C1qa | 12807 | −1.21 | −1.37 ** | −1.75 *** | −1.87 *** |
Csf1r | 18414 | −1.24 | −1.23 | −1.35 * | −1.84 *** |
Gh1 | 11207 | 3.29 *** | −2.03 ** | −1.51 *** | −1.24 |
Snhg11 | 36802 | 1.39 | 3.73 *** | 2.06 *** | 1.31 |
Mt-co3 | 30700 | −1.33 | −1.25 | −1.87 *** | −1.5 *** |
Cacng8 | 57848 | 1.36 * | 2.17 *** | −1.48 | 3.86 * |
Unc13a | 18452 | 1.26 | 1.45 *** | 2.26 *** | 1.28 |
AABR07056156.1 | 61013 | 1.47 * | 3.26 *** | 1.63 | 1.37 |
Abcc5 | 29178 | 1.26 | 2.45 *** | 1.97 *** | 1.14 |
Lpin3 | 16636 | 1.31 | 4.16 *** | 1.53 *** | 1.13 |
Mbp | 16516 | −1.37 | −1.57 ** | −3.17 *** | 1.13 |
AABR07033720.1 | 61472 | 2.56 *** | 2.61 * | 1.42 | −1.72 |
Nr4a2 | 05600 | 1.19 | −1.22 | −1.53 * | 3.23 *** |
Cfd | 33564 | −1.34 | −2.31 | −2.93 | −2.52 *** |
Sppl2a | 11652 | −2.01 *** | −1.08 | −1.5 ** | −1.45 |
Mcc_1 | 62232 | −92.32 *** | 1.15 | NE | NE |
Myorg | 23208 | −1.52 *** | −1.5 * | −1.43 | 1.06 |
Plk5 | 34102 | 1.57 | 1.95 ** | 2.14 *** | 1.12 |
Rpp30 | 18718 | 1.11 | 3.14 ** | 1.64 ** | 1.14 |
Bpifa1 | 13859 | 1.98 | 3.86 | 62.13 *** | −2.87 |
L3mbtl1 | 07044 | 1.52 * | 5.24 *** | 2.61 *** | −1.02 |
AABR07065531.26 | 59660 | 1.22 | 4.38 *** | 1.63 * | −1.11 |
Scx | 21812 | 8.03 ** | 7.59 | −1.09 | 11.05 *** |
Ints10 | 55331 | 1.02 | 2.58 *** | 1.49 *** | 1.2 |
Mobp | 18700 | −1.3 | −1.45 * | −16.55 *** | 1.01 |
Tspoap1 | 07957 | 1.04 | 1.15 | 1.96 *** | 1.42 |
Tmem125_2 | 45872 | −6.98 *** | 1.75 | 1.14 | NE |
Slc17a7 | 20650 | 3.89 *** | 1.4 | 1.07 | −4.61 |
AABR07000411.1 | 55789 | 3.63 *** | 2.31 | 1.17 | 1.07 |
Nadsyn1 | 20736 | 1.14 | 1.23 | 1.95 *** | 1.1 |
Adamts18 | 11575 | 2.79 *** | −1.03 | 3.35 | 1.34 |
Acsm5 | 31211 | 1.08 | 1.02 | 1.25 | −7.91 *** |
Ddn | 59605 | 1.13 | 1.12 | −16.74 *** | 1.02 |
Cwc25 | 04091 | 1.04 | 1.02 | 1.09 | 3.17 *** |
Cd300c2 | 46216 | 1.06 | −1.02 | −1.13 | −2.7 *** |
LOC690507 | 15637 | NE | NE | NE | 9.5 *** |
Rank | Attribute | Gene Name | Weight | Sum of Weights | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Info Gain Ratio | Rule | Chi Squared | Gini Index | Uncertainty | Relief | Info Gain | ||||
1 | ENSRNOG00000019544 | Zbtb2 | 1.0 | 0.8 | 0.9 | 1.0 | 0.9 | 0.6 | 1.0 | 6.1 |
2 | ENSRNOG00000062155 | AC134224.2 | 0.8 | 0.5 | 0.9 | 0.9 | 0.8 | 0.9 | 0.8 | 5.6 |
3 | ENSRNOG00000051490 | Plcg1 | 0.6 | 1.0 | 0.8 | 0.6 | 0.7 | 0.9 | 0.6 | 5.2 |
4 | ENSRNOG00000002194 | Coq2 | 0.9 | 0.6 | 0.7 | 0.9 | 0.7 | 0.6 | 0.9 | 5.1 |
5 | ENSRNOG00000009990 | Zranb2 | 0.8 | 0.3 | 0.8 | 0.8 | 0.8 | 1.0 | 0.8 | 5.1 |
6 | ENSRNOG00000000975 | Mcoln1 | 0.6 | 0.6 | 1.0 | 0.6 | 0.9 | 0.8 | 0.6 | 5.1 |
7 | ENSRNOG00000021061 | Map4k2 | 0.6 | 1.0 | 0.8 | 0.6 | 0.7 | 0.8 | 0.6 | 5.0 |
8 | ENSRNOG00000042258 | RGD1561157 | 0.9 | 0.6 | 0.9 | 0.7 | 0.9 | 0.4 | 0.7 | 5.0 |
9 | ENSRNOG00000030721 | Fbrsl1 | 0.7 | 0.4 | 0.7 | 0.8 | 0.7 | 0.9 | 0.7 | 4.9 |
10 | ENSRNOG00000053405 | Rpap3 | 0.7 | 0.2 | 0.9 | 0.7 | 0.9 | 0.8 | 0.7 | 4.9 |
11 | ENSRNOG00000001010 | Tecpr1 | 0.7 | 1.0 | 0.7 | 0.5 | 0.6 | 0.7 | 0.6 | 4.8 |
12 | ENSRNOG00000057284 | Cenpb | 0.8 | 1.0 | 0.8 | 0.6 | 0.7 | 0.3 | 0.6 | 4.8 |
13 | ENSRNOG00000052539 | Prpf40b | 0.6 | 1.0 | 0.8 | 0.6 | 0.7 | 0.5 | 0.6 | 4.7 |
14 | ENSRNOG00000017621 | Spns1 | 0.7 | 0.4 | 0.7 | 0.8 | 0.6 | 1.0 | 0.7 | 4.7 |
15 | ENSRNOG00000025711 | Spout1 | 0.6 | 1.0 | 0.7 | 0.6 | 0.6 | 0.7 | 0.5 | 4.7 |
16 | ENSRNOG00000020791 | Ube2q1 | 0.8 | 1.0 | 0.8 | 0.6 | 0.8 | 0.1 | 0.6 | 4.7 |
17 | ENSRNOG00000010732 | RGD1561590 | 0.7 | 1.0 | 0.7 | 0.5 | 0.7 | 0.5 | 0.6 | 4.7 |
18 | ENSRNOG00000042195 | Pabpn1 | 0.7 | 0.4 | 0.8 | 0.6 | 0.7 | 1.0 | 0.5 | 4.6 |
19 | ENSRNOG00000014044 | Pank4 | 0.7 | 0.5 | 0.7 | 0.7 | 0.7 | 0.7 | 0.7 | 4.6 |
20 | ENSRNOG00000012807 | C1qa | 0.6 | 0.9 | 0.8 | 0.6 | 0.7 | 0.5 | 0.5 | 4.6 |
6246 | Region/Tissue | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.7 | 0.0 | 0.7 |
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Govic, A.; Nasser, H.; Levay, E.A.; Zelko, M.; Ebrahimie, E.; Mohammadi Dehcheshmeh, M.; Kent, S.; Penman, J.; Hazi, A. Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat. Nutrients 2022, 14, 4670. https://doi.org/10.3390/nu14214670
Govic A, Nasser H, Levay EA, Zelko M, Ebrahimie E, Mohammadi Dehcheshmeh M, Kent S, Penman J, Hazi A. Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat. Nutrients. 2022; 14(21):4670. https://doi.org/10.3390/nu14214670
Chicago/Turabian StyleGovic, Antonina, Helen Nasser, Elizabeth A. Levay, Matt Zelko, Esmaeil Ebrahimie, Manijeh Mohammadi Dehcheshmeh, Stephen Kent, Jim Penman, and Agnes Hazi. 2022. "Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat" Nutrients 14, no. 21: 4670. https://doi.org/10.3390/nu14214670