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

Hövel, Friederike Freiin von; Leiter, Ina; Rumpel, Regina; Langenhagen, Alina; Wedekind, Dirk; Häger, Christine; Bleich, André; Palme, Rupert; Grothe, Claudia

doi:10.1016/j.bbr.2019.112113

Cited by 6 publications

(12 citation statements)

References 45 publications

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“…Furthermore, loss of FGF-2 was associated with hyperactivity and anxiety-like behavior in rodents due to imbalances in the glutamatergic and DA system as well as reduced hippocampal glucocorticoid receptors [117,118]. However, separated from the reported physical differences, no significant psychiatric alterations have been described in adult FGF-2 isoform-specific ko mice regarding their anxiety-like behavior, despite there being a slight tendency for reduced locomotor activity in male FGF-2LMWko mice, which, in contrast, was increased in FGF-2HMWko mice [22].…”

Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 88%

“…Interestingly, this was also true for FGF-2HMWko, despite being attenuated. Furthermore, it was confirmed that FGF-2LMW is the prominent FGF-2 isoform in wt mice during the embryonic stage, which was even more pronounced in FGF-2HMWko [21,22]. So far, compensatory upregulation of other FGFs or their receptors through development of the DA system has only been excluded for FGF-2ko mice [114], but was elusive for isoform-specific ko mice.…”

Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 94%

“…Apart from neurogenesis, FGF-2 also exerts multiple roles in neural cells that include cell proliferation, migration, synaptogenesis, survival and differentiation [18,[98][99][100][101]. Due to these multifaceted neural effects, FGF-2 was shown to be involved in many neurologic and neurodegenerative diseases such as epilepsy, Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) as well as psychiatric disorders including anxiety, autism spectrum disorder (ASD), depression, schizophrenia and drug-related abusive disorders [22,[102][103][104][105][106][107][108][109][110][111][112].…”

Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 99%

“…Furthermore, extensive investigations of FGF-2ko mice were conducted to evaluate loss of function, but without closer differentiation with regard to FGF-2 isoforms. So far, isoform-specific ko mice have only been employed to study dopaminergic (DA) nigral neurons and motor neurons (ALS mouse model) (Table 3) [22,113]. Regarding the nigrostriatal pathway, which is especially affected in PD, it was demonstrated that through maturation, mice lacking either FGF-2LMW or FGF-2HMW develop more DA neurons within the substantia nigra (SN) pars compacta, equally distributed to the hyperplasia phenotype previously described for adult mice lacking FGF-2 [99].…”

Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 99%

“…In rodents, only three FGF-2 isoforms exist; whereby, the 18 kDa FGF-2LMW isoform can be distinguished from two FGF-2HMW (21 and 22 kDa) isoforms [16][17][18][19]. Furthermore, protein expression of all known isoforms was demonstrated to differ regarding the tissue and the developmental stage [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Hövel

Kefalakes

Grothe

2020

IJMS

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Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.

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Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 88%

Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 94%

Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 99%

Section: Fgf-2 Isoforms In the Central Nervous Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Hövel

Kefalakes

Grothe

2020

IJMS

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Extracellular matrix protein anosmin-1 overexpression alters dopaminergic phenotype in the CNS and the PNS with no pathogenic consequences in a MPTP model of Parkinson’s disease

et al. 2023

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The development and survival of dopaminergic neurons are influenced by the fibroblast growth factor (FGF) pathway. Anosmin-1 (A1) is an extracellular matrix protein that acts as a major regulator of this signaling pathway, controlling FGF diffusion, and receptor interaction and shuttling. In particular, previous work showed that A1 overexpression results in more dopaminergic neurons in the olfactory bulb. Prompted by those intriguing results, in this study, we investigated the effects of A1 overexpression on different populations of catecholaminergic neurons in the central (CNS) and the peripheral nervous systems (PNS). We found that A1 overexpression increases the number of dopaminergic substantia nigra pars compacta (SNpc) neurons and alters the striosome/matrix organization of the striatum. Interestingly, these numerical and morphological changes in the nigrostriatal pathway of A1-mice did not confer an altered susceptibility to experimental MPTP-parkinsonism with respect to wild-type controls. Moreover, the study of the effects of A1 overexpression was extended to different dopaminergic tissues associated with the PNS, detecting a significant reduction in the number of dopaminergic chemosensitive carotid body glomus cells in A1-mice. Overall, our work shows that A1 regulates the development and survival of dopaminergic neurons in different nuclei of the mammalian nervous system.

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Fibroblast Growth Factor Signalling in the Diseased Nervous System

Klimaschewski

Claus

2021

Mol Neurobiol

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Fibroblast growth factors (FGFs) act as key signalling molecules in brain development, maintenance, and repair. They influence the intricate relationship between myelinating cells and axons as well as the association of astrocytic and microglial processes with neuronal perikarya and synapses. Advances in molecular genetics and imaging techniques have allowed novel insights into FGF signalling in recent years. Conditional mouse mutants have revealed the functional significance of neuronal and glial FGF receptors, not only in tissue protection, axon regeneration, and glial proliferation but also in instant behavioural changes. This review provides a summary of recent findings regarding the role of FGFs and their receptors in the nervous system and in the pathogenesis of major neurological and psychiatric disorders.

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

Cited by 6 publications

References 45 publications

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Extracellular matrix protein anosmin-1 overexpression alters dopaminergic phenotype in the CNS and the PNS with no pathogenic consequences in a MPTP model of Parkinson’s disease

Fibroblast Growth Factor Signalling in the Diseased Nervous System

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