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Status |
Public on Dec 07, 2022 |
Title |
Age-associated downregulation of glutamate and GABA neurotransmission-related gene expression in the rostral ventrolateral medulla of male Fischer 344 rats |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by RT-PCR
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Summary |
The rostral ventrolateral medulla (RVLM), a part of the medullary reticular formation, plays a major role in several physiological responses, including cardiovascular and sympathetic nervous system functions. Although aging causes disturbances in the responses of these physiological systems, RVLM involvement in these age-related changes is not clear. Previous work using high-throughput gene expression analysis of the RVLM in aged animals suggested that chemical neurotransmission-related genes might be downregulated with advancing age. Since the RVLM function involves a balance of inhibitory and excitatory inputs, which is largely mediated by gamma-aminobutyric acid (GABA) and excitatory amino acid (EAA) neurotransmission, we hypothesized that aging is associated with altered excitatory and/or inhibitory neurotransmission-related gene expression in the RVLM. To test this hypothesis, we micropunched an RVLM-containing area from young (3–5 months), middle-aged (12–14 months), and aged (22–26 months) Fischer 344 male rats. RNA purified from these micropunches was analyzed using GABA and Glutamate RT2 Profiler PCR arrays (n= 8–10). In addition, the expression of selected genes was validated at the RNA level using TaqMan® based- qPCR and at the protein level using western blotting. All the genes that displayed significant differential expression (1.5-fold, p < .05, FDR < .05) were identified to be downregulated in the RVLM of aged and middle-aged rats compared to young rats. Among the downregulated genes, the percentage of glutamate neurotransmission-related genes was higher than GABA neurotransmission-related genes. Solute carrier family 1 member 6 (Slc1a6) gene showed the highest fold downregulation at the RNA level in the RVLM of aged compared to young rats, and its protein product, Excitatory amino acid transporter 4 (EAAT4), showed a downregulatory trend in the RVLM of aged and middle-aged rats. These results suggest that molecular constituents of both GABA and glutamate neurotransmission might be altered in the RVLM of aged and middle-aged rats, and the changes in glutamate neurotransmission might be more prominent. Investigating age-associated anatomical and functional changes in RVLM GABA and glutamate neurotransmission might provide a foundation for understanding the effects of aging on physiological function.
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Overall design |
Rostral ventrolateral medulla (RVLM) containing lower brainstem area was micropunched from young (3–5 months, 304 ± 7 g, n=8), middle-aged (12–14 months, 425 ± 8 g, n=8), and aged (22–26 months, 432 ± 11 g, n=8) male Fischer 344 rats. RNA collected from these tissue punches was analyzed using Rat GABA & Glutamate RT2 Profiler PCR arrays (Qiagen, Inc., GeneGlobe ID PARN-152Z).
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Contributor(s) |
Balivada S, Tapia GP, Pawar HN, Khan AM, Kenney MJ |
Citation missing |
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NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 AG041948 |
Sympathetic Neural Regulation and Aging: Medullary Mechanisms and Strategies |
KANSAS STATE UNIVERSITY |
Michael J Kenney |
SC1 GM127251 |
Interrogating brain circuits that control feeding caused by fasting or by craving |
UNIVERSITY OF TEXAS EL PASO |
ARSHAD M. KHAN |
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Submission date |
Dec 07, 2022 |
Last update date |
Dec 07, 2022 |
Contact name |
Sivasai Balivada |
E-mail(s) |
sbalivada@utep.edu
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Phone |
7854777070
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Organization name |
University of Texas at El Paso
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Street address |
4th floor, Bioscience research building
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City |
El Paso |
State/province |
Texas |
ZIP/Postal code |
79968 |
Country |
USA |
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Platforms (1) |
GPL32921 |
Qiagen Rat GABA & Glutamate RT2 Profiler PCR assay |
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Samples (26)
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GSM6797916 |
Young RVLM, set1, biological replicate 1 |
GSM6797917 |
Young RVLM, set1, biological replicate 2 |
GSM6797918 |
Young RVLM, set1, biological replicate 3 |
GSM6797919 |
Young RVLM, set1, biological replicate 4 |
GSM6797920 |
Young RVLM, set1, biological replicate 5 |
GSM6797921 |
Young RVLM, set2, biological replicate 6 |
GSM6797922 |
Young RVLM, set2, biological replicate 7 |
GSM6797923 |
Young RVLM, set2, biological replicate 8 |
GSM6797924 |
Middle-aged RVLM, set1, biological replicate 1 |
GSM6797925 |
Middle-aged RVLM, set1, biological replicate 2 |
GSM6797926 |
Middle-aged RVLM, set1, biological replicate 3 |
GSM6797927 |
Middle-aged RVLM, set1, biological replicate 4 |
GSM6797928 |
Middle-aged RVLM, set1, biological replicate 5 |
GSM6797929 |
Middle-aged RVLM, set2, biological replicate 6 |
GSM6797930 |
Middle-aged RVLM, set2, biological replicate 7 |
GSM6797931 |
Middle-aged RVLM, set2, biological replicate 8 |
GSM6797932 |
Aged RVLM, set1, biological replicate 1 |
GSM6797933 |
Aged RVLM, set1, biological replicate 2 |
GSM6797934 |
Aged RVLM, set1, biological replicate 3 |
GSM6797935 |
Aged RVLM, set1, biological replicate 4 |
GSM6797936 |
Aged RVLM, set1, biological replicate 5 |
GSM6797937 |
Aged RVLM, set2, biological replicate 6 |
GSM6797938 |
Aged RVLM, set2, biological replicate 7 |
GSM6797939 |
Aged RVLM, set2, biological replicate 8 |
GSM6797940 |
Aged RVLM, set2, biological replicate 9 |
GSM6797941 |
Aged RVLM, set2, biological replicate 10 |
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Relations |
BioProject |
PRJNA909594 |
Supplementary file |
Size |
Download |
File type/resource |
GSE220296_Fold_change.xlsx |
13.5 Kb |
(ftp)(http) |
XLSX |
GSE220296_Matrix_non-normalized.xlsx |
40.0 Kb |
(ftp)(http) |
XLSX |
Processed data included within Sample table |
Processed data are available on Series record |
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