Selective Ablation of BDNF from Microglia Reveals Novel Roles in Self-Renewal and Hippocampal Neurogenesis

Harley, Samuel; Willis, Emily F.; Shaikh, Samreen; Blackmore, Daniel G.; Sah, Pankaj; Ruitenberg, Marc J.; Bartlett, Perry F.; Vukovic, Jana

doi:10.1523/jneurosci.2539-20.2021

Cited by 32 publications

(20 citation statements)

References 64 publications

(76 reference statements)

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“…In agreement with our results, it has been shown that repeated administration of cocaine leads to a reduction of this neurotrophic factor in the hippocampus 78 , 79 . Although microglia may not represent the main source of BDNF in the brain, the release of this neurotrophin by these cells seems to be important in physiological and pathological conditions 80 . In addition, it has been shown that BDNF synthesis and release are regulated by a plethora of events and circumstances, such as altered levels of ions, depolarization, neurotransmitters, hormones, inflammatory mediators, among others 81 .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of CSF1R, a receptor involved in microglia viability, alters behavioral and molecular changes induced by cocaine

Silva

Gomes

Fernandes

et al. 2021

Sci Rep

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Different data suggest that microglia may participate in the drug addiction process as these cells respond to neurochemical changes induced by the administration of these substances. In order to study the role of microglia in drug abuse, Swiss mice aged 8–9 weeks were treated with the CSF1R inhibitor PLX3397 (40 mg/kg, p.o.) and submitted to behavioral sensitization or conditioned place preference (CPP) induced by cocaine (15 mg/kg, i.p.). Thereafter, brains were used to evaluate the effects of CSF1R inhibition and cocaine administration on morphological, biochemical and molecular changes. CSF1R inhibition attenuated behavioral sensitization, reduced the number of Iba-1+ cells and increased ramification and lengths of the branches in the remaining microglia. Additionally, both cocaine and PLX3397 increased the cell body to total cell size ratio of Iba-1+ cells, as well as CD68+ and GFAP+ stained areas, suggesting an activated pattern of the glial cells. Besides, CSF1R inhibition increased CX3CL1 levels in the striatum, prefrontal cortex and hippocampus, as well as reduced CX3CR1 expression in the hippocampus. In this region, cocaine also reduced BDNF levels, an effect that was enhanced by CSF1R inhibition. In summary, our results suggest that microglia participate in the behavioral and molecular changes induced by cocaine. This study contributes to the understanding of the role of microglia in cocaine addiction.

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Section: Discussionmentioning

confidence: 99%

Inhibition of CSF1R, a receptor involved in microglia viability, alters behavioral and molecular changes induced by cocaine

Silva

Gomes

Fernandes

et al. 2021

Sci Rep

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“…Moreover, microglia provide trophic support to their neighboring cells by secreting neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF) and Insulin-like Growth Factor (IGF), thereby regulating neuronal function and synapse formation [ 29 , 43 , 44 ]. In turn, NGF and BDNF can regulate microglial functions [ 13 , 14 , 45 , 46 , 47 , 48 ].…”

Section: Microglia In Health and Neurodegenerative Diseasementioning

confidence: 99%

The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives

Alexaki

2021

Cells

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Increased life expectancy in combination with modern life style and high prevalence of obesity are important risk factors for development of neurodegenerative diseases. Neuroinflammation is a feature of neurodegenerative diseases, and microglia, the innate immune cells of the brain, are central players in it. The present review discusses the effects of obesity, chronic peripheral inflammation and obesity-associated metabolic and endocrine perturbations, including insulin resistance, dyslipidemia and increased glucocorticoid levels, on microglial function.

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“…Microglia are the brain-resident innate immune cells with increasingly recognized roles in neuronal function and brain homeostasis, which includes the control of the neurogenic niche in the adult hippocampus [ 417 ]. Microglia have been shown to be a relevant cellular component part of the neurogenic niche [ 418 ] and to physiologically regulate hippocampal adult neurogenesis at multiple steps of the neurogenesis process, using phagocytosis secretome [ 419 , 420 ], signaling through the CX3C-receptor-1 (CX3CR1) [ 421 , 422 ], and the release of BDNF [ 423 ]. In addition, experiments of microglia ablation suggest that microglia are required for basal hippocampal neurogenesis [ 424 ].…”

Section: Mechanisms Of Stress Acting On Neurogenesismentioning

confidence: 99%

Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

Leschik

Lutz

Gentile

2021

IJMS

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Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.

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Selective Ablation of BDNF from Microglia Reveals Novel Roles in Self-Renewal and Hippocampal Neurogenesis

Cited by 32 publications

References 64 publications

Inhibition of CSF1R, a receptor involved in microglia viability, alters behavioral and molecular changes induced by cocaine

Inhibition of CSF1R, a receptor involved in microglia viability, alters behavioral and molecular changes induced by cocaine

The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives

Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

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