Fibroblast Growth Factor 2 Modulates Hypothalamic Pituitary Axis Activity and Anxiety Behavior Through Glucocorticoid Receptors

Salmaso, Natalina; Stevens, Hanna E.; McNeill, Jessica; Elsayed, Maha; Ren, Qiuyin; Maragnoli, Maria Elisabetta; Schwartz, Michael L.; Tomasi, Simone; Sapolsky, Robert M.; Duman, Ronald S.; Vaccarino, Flora M.

doi:10.1016/j.biopsych.2016.02.026

Cited by 53 publications

(70 citation statements)

References 47 publications

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“…The open field test (OFT) was used to assess the influence of paraquat dose on anxiety-like behavior, as previously described by Salmaso et al (2016). The OFT was conducted 3 days following the last paraquat/saline injection.…”

Section: Methodsmentioning

confidence: 99%

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Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

Rudyk

McNeill

Prowse

et al. 2017

Front. Aging Neurosci.

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Little is known of the age-dependent and long-term consequences of low exposure levels of the herbicide and dopaminergic toxicant, paraquat. Thus, we assessed the dose-dependent effects of paraquat using a typical short-term (3 week) exposure procedure, followed by an assessment of the effects of chronic (16 weeks) exposure to a very low dose (1/10th of what previously induced dopaminergic neuronal damage). Short term paraquat treatment dose-dependently induced deficits in locomotion, sucrose preference and Y-maze performance. Chronic low dose paraquat treatment had a very different pattern of effects that were also dependent upon the age of the animal: in direct contrast to the short-term effects, chronic low dose paraquat increased sucrose consumption and reduced forced swim test (FST) immobility. Yet these effects were age-dependent, only emerging in mice older than 13 months. Likewise, Y-maze spontaneous alternations and home cage activity were dramatically altered as a function of age and paraquat chronicity. In both the short and long-term exposure studies, increased corticosterone and altered hippocampal glucocorticoid receptor (GR) levels were induced by paraquat, but surprisingly these effects were blunted in the older mice. Thus, paraquat clearly acts as a systemic stressor in terms of corticoid signaling and behavioral outcomes, but that paradoxical effects may occur with: (a) repeated exposure at; (b) very low doses; and (c) older age. Collectively, these data raise the possibility that repeated “hits” with low doses of paraquat in combination with aging processes might have promoted compensatory outcomes.

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Section: Methodsmentioning

confidence: 99%

“…To further measure anxiety-like behavior, the elevated plus maze (EPM) was used, as previously described (Salmaso et al, 2016). The EPM consists of four arms (24.8 cm long × 7 cm wide) with two closed arms enclosed by 21 cm high walls and elevated approximately 60 cm off the surface of the floor.…”

Section: Methodsmentioning

confidence: 99%

Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

Rudyk

McNeill

Prowse

et al. 2017

Front. Aging Neurosci.

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“…Interestingly, this effect may not be restricted to neurons as imipramine application on cultured rat astrocytes up-regulates EGR1 expression in a MAPK-dependent manner, which then binds to the glial cell line-derived neurotrophic factor ( gdnf ) gene promoter and activates its expression (Kim et al, 2011). Moreover, while these effects were observed in unstressed systems, which could thus be considered at baseline, experimental interventions exerting an antidepressant-like effect, such as environmental enrichment, FGF2, or fluoxetine, have also been reported to reverse or protect from induction of anxiety- and depressive-like states in multiple models (Monsey et al, 2014; Novaes et al, 2017; Salmaso et al, 2016). Although causality still remains to be clearly established, the up-regulation of EGR1 following antidepressant treatment thus emerges as a key feature of antidepressant response.…”

Section: Egr1 Role In Pathological Statesmentioning

confidence: 99%

The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders

Duclot

Kabbaj

2017

Front. Behav. Neurosci.

281

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It is now clearly established that complex interactions between genes and environment are involved in multiple aspects of neuropsychiatric disorders, from determining an individual’s vulnerability to onset, to influencing its response to therapeutic intervention. In this perspective, it appears crucial to better understand how the organism reacts to environmental stimuli and provide a coordinated and adapted response. In the central nervous system, neuronal plasticity and neurotransmission are among the major processes integrating such complex interactions between genes and environmental stimuli. In particular, immediate early genes (IEGs) are critical components of these interactions as they provide the molecular framework for a rapid and dynamic response to neuronal activity while opening the possibility for a lasting and sustained adaptation through regulation of the expression of a wide range of genes. As a result, IEGs have been tightly associated with neuronal activity as well as a variety of higher order processes within the central nervous system such as learning, memory and sensitivity to reward. The immediate early gene and transcription factor early growth response 1 (EGR1) has thus been revealed as a major mediator and regulator of synaptic plasticity and neuronal activity in both physiological and pathological conditions. In this review article, we will focus on the role of EGR1 in the central nervous system. First, we will summarize the different factors influencing its activity. Then, we will analyze the amount of data, including genome-wide, that has emerged in the recent years describing the wide variety of genes, pathways and biological functions regulated directly or indirectly by EGR1. We will thus be able to gain better insights into the mechanisms underlying EGR1’s functions in physiological neuronal activity. Finally, we will discuss and illustrate the role of EGR1 in pathological states with a particular interest in cognitive functions and neuropsychiatric disorders.

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“…Furthermore, increased anxiety, dysregulation of the hypothalamic pituitary axis and decreased hippocampal glucocorticoid receptor expression is observed in FGF2 knockout mice. These effects are reversible by administration of FGF2 (Salmaso et al, 2016). FGF22 and FGF7 are presynaptic organizing molecules that promote differentiation of excitatory and inhibitory presynaptic terminals in the hippocampal cornu ammonis (CA) region 3 through combinatorial signaling of sets of FGFRs (Umemori et al, 2004; Terauchi et al, 2010; Dabrowski et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia

Choubey

Collette

Smith

2017

PeerJ

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BackgroundFibroblast growth factors (FGFs) and their receptors (FGFRs) have numerous functions in the developing and adult central nervous system (CNS). For example, the FGFR1 receptor is important for proliferation and fate specification of radial glial cells in the cortex and hippocampus, oligodendrocyte proliferation and regeneration, midline glia morphology and soma translocation, Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1 signaling in astrocytes is required for postnatal maturation of interneurons expressing parvalbumin (PV). FGFR1 is implicated in synapse formation in the hippocampus, and alterations in the expression of Fgfr1 and its ligand, Fgf2 accompany major depression. Understanding which cell types express Fgfr1 during development may elucidate its roles in normal development of the brain as well as illuminate possible causes of certain neuropsychiatric disorders.MethodsHere, we used a BAC transgenic reporter line to trace Fgfr1 expression in the developing postnatal murine CNS. The specific transgenic line employed was created by the GENSAT project, tgFGFR1-EGFPGP338Gsat, and includes a gene encoding enhanced green fluorescent protein (EGFP) under the regulation of the Fgfr1 promoter, to trace Fgfr1 expression in the developing CNS. Unbiased stereological counts were performed for several cell types in the cortex and hippocampus.ResultsThis model reveals that Fgfr1 is primarily expressed in glial cells, in both astrocytes and oligodendrocytes, along with some neurons. Dual labeling experiments indicate that the proportion of GFP+ (Fgfr1+) cells that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating dynamic changes in Fgfr1 expression during postnatal development of the cortex. In postnatal neurogenic areas, GFP expression was also observed in SOX2, doublecortin (DCX), and brain lipid-binding protein (BLBP) expressing cells. Fgfr1 is also highly expressed in DCX positive cells of the dentate gyrus (DG), but not in the rostral migratory stream. Fgfr1 driven GFP was also observed in tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and astrocytes of the cerebellum.ConclusionsThe tgFGFR1-EGFPGP338Gsat mouse model expresses GFP that is congruent with known functions of FGFR1, including hippocampal development, glial cell development, and stem cell proliferation. Understanding which cell types express Fgfr1 may elucidate its role in neuropsychiatric disorders and brain development.

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Fibroblast Growth Factor 2 Modulates Hypothalamic Pituitary Axis Activity and Anxiety Behavior Through Glucocorticoid Receptors

Abstract: These data suggest that FGF2 levels are critically related to anxiety behavior and hypothalamic-pituitary-adrenal axis activity, likely through modulation of hippocampal glucocorticoid receptor expression, an effect that is likely receptor mediated, albeit not by FGFR1, FGFR2, and FGFR3.

Cited by 53 publications

References 47 publications

Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders

Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia

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