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Tapia, G. P.

Publications and source records attributed to Tapia, G. P..

2 recordsLinked to original sources
bioRxiv2022

Age-associated downregulation of glutamate and GABA neurotransmission-related gene expression in the rostral ventrolateral medulla of male Fischer 344 rats

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 RVLM function involves a balance of signals from 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). Each profiler array has primers for 84 GABA and glutamate neurotransmission related genes. In addition, the expression of selected genes was validated at the RNA level using TaqMan(R) 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. This downregulation did not appear to be a result of RVLM tissue sampling differences among the age groups, since a separate validation of our sampling method, which involved careful mapping of micropunched regions to a standardized brain atlas, revealed no spatial differences in sampled sites among age groups. Among the downregulated genes, the percentage of glutamate neurotransmission-related genes was higher than GABA neurotransmission-related genes. The 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.

neuroscience↗
bioRxiv2022

Glycemic challenge is associated with the rapid cellular activation of the locus ceruleus and nucleus of solitary tract: Circumscribed spatial analysis of phosphorylated MAP kinase immunoreactivity in relation to catecholaminergic and cholinergic chemoarchitecture

Rodent studies indicate that impaired glucose utilization or hypoglycemia is associated with cellular activation of neurons in the medulla (Winslow, 1733) (MY) believed to control feeding behavior and glucose counterregulation. However, such activation has been tracked primarily within hours of the challenge, rather than sooner, and has been poorly mapped within standardized brain atlases. Here, we report that within 15 min of receiving 2-deoxy-D-glucose (2-DG; 250 mg/kg, i.v.), which can trigger glucoprivic feeding behavior, marked elevations were observed in the numbers of rhombic brain (His, 1893) (RB) neuronal cell profiles immunoreactive for the cellular activation marker(s), phosphorylated p44/42 MAP kinases (phospho-ERK1/2), some of which were also catecholaminergic. We mapped their distributions within an open-access rat brain atlas and found that 2-DG-treated rats (compared to their saline-treated controls) displayed greater numbers of phospho-ERK1/2+ neurons in the locus ceruleus (Wenzel & Wenzel, 1812) (LC) and the nucleus of solitary tract (>1840) (NTS). Thus, 2-DG-activation of certain RB neurons is more rapid than perhaps previously realized, engaging neurons that serve multiple functional systems and are of varying cellular phenotypes. Mapping these populations within standardized brain atlas maps streamlines their targeting and/or comparable mapping in preclinical rodent models of disease.

neuroscience↗