Visualizing BDNF cell-to-cell transfer reveals astrocytes are the primary recipient of neuronal BDNF

Stahlberg, Markus A.; Kügler, Sebastian; Dean, Camin

doi:10.1101/255935

Cited by 11 publications

(14 citation statements)

References 72 publications

(86 reference statements)

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“…Interestingly, TBS activity is likely to induce elevated extracellular potassium levels. Consistent with this, BDNF release from astrocytes was also shown to be induced by elevated extracellular potassium concentration (Stahlberg et al 2018;Vignoli and Canossa 2017). However, HFS was ineffective in releasing recycled BDNF from pure astrocytic cultures (Bergami et al 2008).…”

Section: Bdnf Release From Astrocytessupporting

confidence: 55%

“…Whether neuronal and astrocytic recyclings of BDNF coexist or whether they are successive processes need to be clarified. In contrast to the endocytosis of pro-BDNF, another study suggests that solely the mature form of BDNF is endocytosed by astrocytes via truncated TrkB receptors in dissociated cultures (Stahlberg et al 2018). Interestingly, inflammatory stimuli like released interferongamma increased astrocytic expression of truncated TrkB, which was associated with increased BDNF recycling capacity of astrocytes (Rubio 1997).…”

Section: Bdnf Release From Astrocytesmentioning

confidence: 99%

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The physiology of regulated BDNF release

2020

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The neurotrophic factor BDNF is an important regulator for the development of brain circuits, for synaptic and neuronal network plasticity, as well as for neuroregeneration and neuroprotection. Up- and downregulations of BDNF levels in human blood and tissue are associated with, e.g., neurodegenerative, neurological, or even cardiovascular diseases. The changes in BDNF concentration are caused by altered dynamics in BDNF expression and release. To understand the relevance of major variations of BDNF levels, detailed knowledge regarding physiological and pathophysiological stimuli affecting intra- and extracellular BDNF concentration is important. Most work addressing the molecular and cellular regulation of BDNF expression and release have been performed in neuronal preparations. Therefore, this review will summarize the stimuli inducing release of BDNF, as well as molecular mechanisms regulating the efficacy of BDNF release, with a focus on cells originating from the brain. Further, we will discuss the current knowledge about the distinct stimuli eliciting regulated release of BDNF under physiological conditions.

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Section: Bdnf Release From Astrocytessupporting

confidence: 55%

Section: Bdnf Release From Astrocytesmentioning

confidence: 99%

The physiology of regulated BDNF release

2020

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“…Our previous study demonstrated that the activation of mTORC1 induced by Rheb(S16H) transduction of hippocampal neurons causes BDNF production, which protects against thrombin-induced neurotoxicity in the rat hippocampus [16]. Another study showed that astrocytes are the primary recipient cells of neuronal BDNF in the visual system [39]. Astrocytic CNTF mediates neuronal survival, neurogenesis, and neuronal plasticity through CNTFRα binding in the central nervous system [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of AAV1-Rheb(S16H) Transduction Against Alzheimer’s Disease

Moon

Kim

Jeon

et al. 2019

JCM

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We recently reported that adeno-associated virus serotype 1-constitutively active Ras homolog enriched in brain [AAV1-Rheb(S16H)] transduction of hippocampal neurons could induce neuron-astroglia interactions in the rat hippocampus in vivo, resulting in neuroprotection. However, it remains uncertain whether AAV1-Rheb(S16H) transduction induces neurotrophic effects and preserves the cognitive memory in an animal model of Alzheimer’s disease (AD) with characteristic phenotypic features, such as β-amyloid (Aβ) accumulation and cognitive impairments. To assess the therapeutic potential of Rheb(S16H) in AD, we have examined the beneficial effects of AAV1-Rheb(S16H) administration in the 5XFAD mouse model. Rheb(S16H) transduction of hippocampal neurons in the 5XFAD mice increased the levels of neurotrophic signaling molecules, including brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), and their corresponding receptors, tropomyosin receptor kinase B (TrkB) and CNTF receptor α subunit (CNTFRα), respectively. In addition, Rheb(S16H) transduction inhibited Aβ production and accumulation in the hippocampus of 5XFAD mice and protected the decline of long-term potentiation (LTP), resulting in the prevention of cognitive impairments, which was demonstrated using novel object recognition testing. These results indicate that Rheb(S16H) transduction of hippocampal neurons may have therapeutic potential in AD by inhibiting Aβ accumulation and preserving LTP associated with cognitive memory.

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“…However, it is important to consider that CB1 also acts as a Gq-coupled receptor, althoush this mechanism is mostly found in slial cells [for review see (Oliveira da Cruz et al, 2016)], and these cells uptake rather than release BDNF (for example (Stahlbers, Kuesler & Dean, 2018). Therefore a CB1-mediated release of BDNF upon calcium influx is an unlikely scenario for the activation of TRKB.…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors (v0.1)"

2019

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Background: administration of anandamide (AEA) or 2-arachidonoylglycerol (2AG) induces CB1 coupling and activation of TRKB receptors, regulating the neuronal migration and maturation in the developing cortex. However, at higher concentrations AEA also engages vanilloid receptor-TRPV1, usually with opposed consequences on behavior. Methods and Results: Using primary cell cultures from the cortex of rat embryos (E18) we determined the effects of AEA on phosphorylated TRKB (pTRK). We observed that AEA (at 100 and 200nM) induced a significant increase in pTRK levels. Such effect of AEA at 100nM was blocked by pretreatment with the CB1 antagonist AM251 (200nM) and, at the higher concentration of 200nM by the TRPV1 antagonist capsazepine (200nM), but mildly attenuated by AM251. Interestingly, the effect of AEA or capsaicin (a TRPV1 agonist, also at 200nM) on pTRK was blocked by TRKB.Fc (a soluble form of TRKB able to bind BDNF) or capsazepine, suggesting a mechanism dependent on BDNF release. Using the marble-burying test (MBT) in mice, we observed that the local administration of ACEA (a CB1 agonist) into the prelimbic region of prefrontal cortex (PL-PFC) was sufficient to reduce the burying behavior, while capsaicin or BDNF exerted the opposite effect, increasing the number of buried marbles. In addition, both ACEA and capsaicin effects were blocked by previous administration of k252a (an antagonist of TRK receptors) into PL-PFC. The effect of systemically injected CB1 agonist WIN55,212-2 was blocked by previous administration of k252a. We also observed a partial colocalization of CB1/TRPV1/TRKB in the PL-PFC, and the localization of TRPV1 in CaMK2+ cells. Conclusion: taken together, our data indicate that anandamide engages a coordinated activation of TRKB, via CB1 and TRPV1. Thus, acting upon CB1 and TRPV1, AEA could regulate the TRKB-dependent plasticity in both pre-and postsynaptic compartments.

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Visualizing BDNF cell-to-cell transfer reveals astrocytes are the primary recipient of neuronal BDNF

Cited by 11 publications

References 72 publications

The physiology of regulated BDNF release

The physiology of regulated BDNF release

Therapeutic Potential of AAV1-Rheb(S16H) Transduction Against Alzheimer’s Disease

Peer Review #1 of "Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors (v0.1)"

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