Increased Locomotor Activity is Associated with Enhanced Tyrosine Hydroxylase Expression in Mice Expressing an Endothelial Cell‐Specific Fibroblast Growth Factor 1 Transgene
Authors: Small Deena J. , Eaton Victoria , Koh Woon Yuen , Langlais Audrie , Bergquist Ivy , Mokler David , Prudovsky Igor 
Published: June 2021

Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental syndrome characterized by hyperactivity, difficulty in focusing on tasks and impulsive behavior. The etiology of ADHD is multifactorial and is strongly associated with abnormal dopamine metabolism. However, the identification of proteins with abnormal expression or function that may contribute to the development of ADHD is still lacking. Fibroblast Growth Factor 1 (FGF1) is a ubiquitous cytokine produced heavily in the brain and neuronal tissue. FGF1 is also released by vascular endothelial cells into surrounding tissue in response to hypoxia and other cellular stressors including saturated fatty acids. We have observed that transgenic mice continuously expressing an endothelial cell‐specific, FGF1 transgene (FGF1‐Tek) are resistant to high fat diet‐induced abdominal adipose accretion and are more metabolically “healthy” than wild type controls. Metabolic chamber analysis indicates that suppression of the development of visceral adiposity and insulin resistance is not associated with alterations in appetite or resting metabolic rate in the FGF1‐Tek strain. Instead, FGF1‐Tek mice display increased locomotor activity characterized by unrelenting “circling behavior” that likely promotes the utilization of dietary fatty acids before they can accumulate in adipose and liver. Further behavioral testing using the open field LMA test, elevated plus maze and Morris water maze suggests that the behavior patterns exhibited by the FGF1‐Tek mice are similar to those found in ADHD including hyperactivity and reductions in an ability to learn. These behaviors may be linked to increased production of dopamine as the expression of tyrosine hydroxylase‐ a key enzyme in the dopamine biosynthetic pathway‐ is significantly upregulated in the brains of FGF1‐Tek mice compared to wild‐type controls. Although FGF1 may be of therapeutic value in the treatment of obesity and metabolic disease, our data suggest that any clinical studies using this potent cytokine should proceed cautiously given the potential for FGF1 to adversely affect behavior and learning.

Support or Funding Information

This work was funded by The American Heart Association grant #11GRNT5870003 to DJ Small; NIH grant HL35627 and MMCRI institutional support to I Prudovsky; NIH COBRE in Stem & Progenitor Cell Biology and Regenerative Medicine grant #NIH/NIGMS P30 GM106391 to D. Wojchowski (physiology core); and NIH COBRE in Study of Pain and Sensory Function, #P20GM103643 to I. Meng (Behavioral and Histology/Imaging Cores). In addition, support for this work was also provided by the UNE Department of Chemistry and Physics, UNE College of Arts and Sciences and The UNE Office of Research and Scholarship.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.