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Behav Brain Res. 2019 Aug 2;374:112113. doi: 10.1016/j.bbr.2019.112113. [Epub ahead of print]

FGF-2 isoforms influence the development of dopaminergic neurons in the murine substantia nigra, but not anxiety-like behavior, stress susceptibility, or locomotor behavior.

Author information

1
Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hanover, Germany; Center for Systems Neuroscience (ZSN), Hanover, Germany.
2
Institute for Laboratory Animal Science, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hanover, Germany.
3
Unit of Physiology, Pathophysiology and Experimental Endocrinology, Department of Biomedical Sciences, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
4
Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hanover, Germany; Center for Systems Neuroscience (ZSN), Hanover, Germany. Electronic address: grothe.claudia@mh-hannover.de.

Abstract

BACKGROUND:

Loss of fibroblast growth factor 2 (FGF-2) is responsible for the development of an increased number of dopaminergic (DA) neurons in the murine substantia nigra pars compacta (SNpc). Furthermore, dysregulation of its expression patterns within the central nervous system (CNS) is associated with behavioral abnormalities in mice. Until now, the contributions of the individual FGF-2 isoforms (one low (LMW) and two high molecular weight (HMW) isoforms) in the CNS are elusive.

METHODS:

To unravel the specific effects of FGF-2 isoforms, we compared three knockout mouse lines, one only deficient for LMW, one deficient for HMW and another lacking both isoforms, regarding DA neuronal development. With this regard, three time points of ontogenic development of the SNpc were stereologically investigated. Furthermore, behavioral aspects were analyzed in young adult mice, supplemented by corticosterone measurements.

RESULTS:

Juvenile mice lacking either LMW or HMW develop equal supernumerary DA neuron numbers in the SNpc. Compensatory increased LMW expression is observed in animals lacking HMW. Meanwhile, no knockout mouse line demonstrated changes in anxiety-like behavior, stress susceptibility, or locomotor behavior.

CONCLUSIONS:

Both FGF-2 isoforms crucially influence DA neuronal development in the murine SNpc. However, absence of LMW or HMW alone alters neither anxiety-like nor locomotor behavior, or stress susceptibility. Therefore, FGF-2 is not a determinant and causative factor for behavioral alterations alone, but probably in combination with appropriate conditions, like environmental or genetic factors.

KEYWORDS:

Behavior; Dopaminergic system development; FGF-2; Glucocorticoids; HMW; LMW

PMID:
31381976
DOI:
10.1016/j.bbr.2019.112113

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