Nutr Res Pract.  2023 Jun;17(3):408-420. 10.4162/nrp.2023.17.3.408.

Dopamine and serotonin alterations by Hizikia fusiformis extracts under in vitro cortical primary neuronal cell cultures

• Jung JW
• Kim YJ
• Choi JS
• Goto Y
• Lee YA

• KMID: 2542839
• DOI: http://doi.org/10.4162/nrp.2023.17.3.408

Abstract

BACKGROUND/OBJECTIVES
Hizikia fusiformis (HF) is a class of brown seaweeds whose active ingredients exert central nervous system protective effects, such as neuroprotection; however, the underlying mechanisms remain unknown. Given that dopamine (DA) and serotonin (5HT) are two major neurotransmitters involved in various psychiatric disorders and neuronal growth in early neurodevelopmental processes, we investigated whether HF extract could modulate the molecular expression associated with DA and 5HT transmission as well as the structural formation of neurons.
MATERIALS/METHODS
in vitro cell cultures were prepared from cerebral cortical neurons obtained from CD-1 mice on embryonic day 14. Cultured cells were treated with 0.1, 1.0, or 10.0 μg/mL of HT extract for 24 h, followed by fluorescence immunostaining for DA and 5HT-related receptors and transporters and some neuronal structural formation-associated molecules.
RESULTS
HF extract dose-dependently upregulated the expression levels of selective DA and 5HT receptors, and downregulated the levels of DA and 5HT transporters. Moreover, HF extract increased the neurofilament light chain expression.
CONCLUSION
These results suggest that HF may modulate DA and 5HT transmission, thereby affecting neurodevelopment.

Keyword

Dopamine; serotonin; seaweed; neuronal outgrowth; psychiatric disorders

Figure

• 

  Fig. 1 Representative images of immunofluorescence staining. (A) Images of stained cells for DRD2 (green) and DRD1 (red). Blue color in the images represents fluorescence staining for cell nuclei with DAPI. (B-G) Similar images for (B) DRD3 (green) and DRD5 (red), (C) NF-L (green) and DRD4 (red), (D) SERT (green) and DAT (red), (E) TH (green) and TPH (red), (F) SYP (green) and 5HT1B (red), and (G) MAP2 (green) and 5HT1A (red).HF, Hizikia fusiformis extract treatment; VEH, vehicle treatment (control); DRD1-5, dopamine D1–5 receptors; DAT, dopamine transporter; DAPI, 4′,6-diamidino-2-phenylindole; NF-L, neurofilament light chain; SERT, serotonin transporter; TH, tyrosine hydroxylase; TPH, tryptophan hydroxylase; SYP, synaptophysin; 5HT1A and 1B, serotonin 1A and 1B receptors; MAP2, microtubule-associated protein 2.

• 

  Fig. 2 Effects of HF extract on the expression levels of molecules associated with DA transmission. (A, B) Raincloud plot illustrating DRD1 expression levels with different doses of HF extract (A) and a graph showing averaged posterior probability distributions (effect size) and 95% confidence intervals (bars on the tops) of it (B). (C-F) Raincloud plots similar to (A), but showing DRD2 (C), DRD3 (D), DRD4 (E), and DRD5 (F) receptor expression levels. (G, H) Raincloud and averaged posterior probability distribution graph similar to (A) and (B), but showing DAT expression. (I) Raincloud plot showing TH expression.DRD1–5, dopamine D1–5 receptors; HF, Hizikia fusiformis extract treatment; VEH, vehicle treatment (control); DAT, dopamine transporter; TH, tyrosine hydroxylase.

• 

  Fig. 3 Effects of HF extract on the expression levels of molecules associated with 5HT transmission. (A, B) Raincloud plot showing 5HT1B expression with different doses of HF extract (A) and a graph showing averaged posterior probability distributions (effect size) and 95% confidence intervals (bars on the tops) of it (B). (C, D) Raincloud and averaged posterior probability distribution graphs similar to (A) and (B), but showing SERT expression. (E, F) Raincloud plots similar to (A, C), but showing TPH (E) and 5HT1A receptor (F) expression levels.5HT1A and 1B, serotonin 1A and 1B receptors; HF, Hizikia fusiformis extract treatment; VEH, vehicle treatment (control); SERT, serotonin transporter; TPH, tryptophan hydroxylase.

• 

  Fig. 4 Effects of HF extract on the expression levels of molecules associated with neural structure formation. (A, B) Raincloud plot showing NF-L expression levels with different doses of HF extract (A) and a graph showing averaged posterior probability distributions (effect size) and 95% confidence intervals (bars on the tops) of it (B). (C, D) Raincloud plots similar to (A), but showing SYP (C) and MAP2 (D) expression levels.NF-L, neurofilament light chain; HF, Hizikia fusiformis extract treatment; VEH, vehicle treatment (control); SYP, synaptophysin; MAP2, microtubule-associated protein 2.

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