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SERT and the Blood‐Brain Barrier: An In‐Depth Analysis of the Male Rat Brain
Author(s) -
Young Lindsey,
Darios Emma,
Watts Stephanie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.834.1
Subject(s) - blood–brain barrier , serotonin , serotonin transporter , anatomy , blood vessel , blood pressure , biology , medicine , endocrinology , pathology , chemistry , central nervous system , receptor
5‐hydroxytryptamine (5‐HT) was originally discovered as a vasoconstrictor. In a previous study, our lab determined that peripheral 5‐HT lowers blood pressure in both normotensive and hypertensive rats. It is unknown if this mechanism occurs centrally or peripherally, and it is debated whether 5‐HT can be transported from the bloodstream to the CNS. The blood‐brain barrier (BBB) is a highly selective barrier that restricts movement of substances from the bloodstream to the CNS and vice‐versa. We hypothesized that the serotonin transporter, SERT, is present in the BBB, and allows for transport of 5‐HT from the bloodstream to the brain. We sampled blood vessels (N=510) using coronal slices of 6 male Sprague‐Dawley rat brains. All slices were between ‐0.26 and 1.60 mm (Bregma) and 8.74 and 10.60 mm (Interaural), determined via hemotoxylin and eosin (H&E) stain. Immunofluorescence was used to determine if SERT and RecA‐1 (an endothelial cell marker) colocalized. Blood vessels were considered to be capillaries if they were larger than 1.5 µm and smaller than 23 µm (measured across their longest intraluminal distance). SERT was identified in the largest pial arteries (mean ± SEM= 228.70 ± 18.71 µm, N=9) and the smallest capillaries (mean ± SEM= 2.79 ± 0.12, N=395).Mean ± SEM (µm) RecA‐1 Positive Capillaries RecA‐1 Positive Pial Arteries SERT Negative 10.20 ± 1.02 (N=39) 129.80 ± 10.12 (N=67) SERT Positive 2.79 ± 0.12 (N=395) 228.70 ± 18.71 (N=9) P‐value <0.0001 (Mann‐Whitney U‐Test) <0.001 (unpaired t‐test)SERT was not identified in blood vessels ranging from 20 to 130 µm (N=45). This distribution was consistent throughout all regions of the brain examined in this study. 5‐HT has the greatest potential to cross the blood‐brain barrier at the opposing ends of the range of vessels observed (1.50 ‐ 317.57 µm). Knowledge of SERT's presence within the blood‐brain barrier will help further understanding of the mechanisms by which 5‐HT functions to decrease blood pressure in rats, and ultimately with regulation of human blood pressure.