Astrocytes in neuroendocrine systems: An overview

Macdonald, Alastair; Robb, Josephine L.; Morrissey, Nicole A.; Beall, Craig; Ellacott, Kate L. J.

doi:10.1111/jne.12726

Cited by 33 publications

(23 citation statements)

References 181 publications

(336 reference statements)

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“…In view of their atypical morphology characterized by elongated processes of the cellular membrane (hence their name derived from star-like cells) that are in physical contact with other cell types and blood vessels, astrocytes facilitate synaptic transmission, neuronal plasticity and survival as well as to regulate blood flow relaying incoming peripheral signals to the CNS 2 . As such astrocytes express a multitude of receptors for hormones and neuropeptides involved in metabolic control and accordingly to the registered signal will react by modulating the neuronal circuitry through increased transport of metabolic factors and release of growth factors, gliotransmitters, metabolites and cytokines 10 . Notwithstanding to these physiological functions, astrocytes also react/adapt to CNS insults such as metabesity-induced neuroinflammation, through a complex and multifaceted process called reactive astrogliosis, characterized by cellular hypertrophy, increased proliferation and altered astrocyte functions 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

Lorenzo¹,

Vázquez²,

López-Noriega³

et al. 2021

Theranostics

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Rationale: We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated in vitro and in vivo in high-fat high-sucrose fed mice. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and reactive astrogliosis. Hmg20a transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. Conclusion: HMG20A coordinates the astrocy...

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Section: Introductionmentioning

confidence: 99%

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

Lorenzo¹,

Vázquez²,

López-Noriega³

et al. 2021

Theranostics

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“…114 Given the increased importance of glial cells in neuroendocrine functions, it is possible that this documented developmental effect of insulin on glial cells could have lasting effects in metabolic regulation. 115…”

Section: Neurode Velopmental Effec Ts Of Insulinmentioning

confidence: 99%

Nutritional and developmental programming effects of insulin

Dearden

Bouret

Ozanne

2021

J Neuroendocrinology

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The discovery of insulin in 1921 was a major breakthrough in medicine and for therapy in patients with diabetes. The dramatic rise in the prevalence of overweight and obesity has been tightly linked to an increased prevalence of gestational diabetes mellitus (GDM), which poses major health concerns. Babies born to GDM mothers are more likely to develop obesity, type 2 diabetes and cardiovascular disease later in life. Evidence accumulated during the past two decades has revealed that high levels insulin, such as those observed during GDM, can have a widespread effect on the development and function of a variety of organs. This review summarises our current knowledge on the role of insulin in the placenta, cardiovascular system and brain during critical periods of development, as well as how it can contribute to lifelong metabolic regulation. We also discuss possible intervention strategies to ameliorate and hopefully reverse the developmental defects associated with obesity and GDM.

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“…As reported in [ 5 ], the integration of hormonal signalling by glial cells occurs in at least two fundamental ways: 1) the hormone acts directly on the glia through specific receptors, which in turn signal to the neuron to modulate its function. Signalling to the neuron may involve secretion of a growth factor, neurohormone, or transmitter-like substance [ 79 ]; and 2) the steroids act first on neurons, to initiate a circular conversation between neurons and astrocytes that ultimately returns to neurons.…”

Section: Steroid Hormones and Neuroinflammation: Biological Mechanisms In Physiological Conditionsmentioning

confidence: 99%

Promising Intervention Approaches to Potentially Resolve Neuroinflammation And Steroid Hormones Alterations in Alzheimer’s Disease and Its Neuropsychiatric Symptoms

Scassellati¹,

Galoforo²,

Esposito³

et al. 2021

Aging and disease

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Astrocytes in neuroendocrine systems: An overview

Cited by 33 publications

References 181 publications

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

Nutritional and developmental programming effects of insulin

Promising Intervention Approaches to Potentially Resolve Neuroinflammation And Steroid Hormones Alterations in Alzheimer’s Disease and Its Neuropsychiatric Symptoms

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