Prostaglandins are powerful inducers of NGF and BDNF production in mouse astrocyte cultures

Toyomoto, Misao; Ohta, Mitsuhiro; Okumura, Kohji; Yano, Hiroe; Matsumoto, Kaori; Inoue, Shintaro; Hayashi, Kyozo; Ikeda, Kiyoshi

doi:10.1016/s0014-5793(04)00246-7

Cited by 92 publications

(58 citation statements)

References 36 publications

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“…Elmariah et al (2004) found GABA A receptor clustering in response to BDNF through Trk-B receptors. Astroglia that we added are also known to produce BDNF in response to activitydependent trans-synaptic signals from prostaglandins (Toyomoto et al, 2004). Together with integrin-mediated astroglial adhesion to neurons, these prostaglandins activate protein kinase C signaling in neurons and excitatory synaptogenesis (Hama et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Added astroglia promote greater synapse density and higher activity in neuronal networks

2007

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Astroglia are known to potentiate individual synapses, but their contribution to networks is unclear.Here we examined the effect of adding either astroglia or media conditioned by astroglia on entire networks of rat hippocampal neurons cultured on microelectrode arrays. Added astroglia increased spontaneous spike rates nearly two-fold and glutamate-stimulated spiking by six-fold, with desensitization eliminated for bath addition of 25 μM glutamate. Astrocyte-conditioned medium partly mimicked the effects of added astroglia. Bursting behavior was largely unaffected by added astroglia except with added glutamate. Addition of the GABA A receptor antagonist bicuculline also increased spike rates but with more subtle differences between networks without or with added astroglia. This indicates that networks without added astroglia were inhibited greatly. In all conditions, the log-log distribution of spike rates fit well to linear distributions over three orders of magnitude. Networks with added astroglia shifted consistently toward higher spike rates. Immunostaining for GFAP revealed a linear increase with added astroglia, which also increased neuronal survival. The increased spike rates with added astroglia correlated with a 1.7-fold increase in immunoreactive synaptophysin puncta, and increases of six-fold for GABA Aβ , two-fold for NMDA-R1 and two-fold for Glu-R1 puncta, with receptor clustering that indicated synaptic scaling. Together, these results indicate that added astroglia increase the density of synapses and receptors, and facilitate higher spike rates for many elements in the network. These effects are reproduced by glia-conditioned media, with the exception of glutamate-mediated transmission.

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Section: Discussionmentioning

confidence: 99%

Added astroglia promote greater synapse density and higher activity in neuronal networks

2007

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“…It has been reported that PGD 2 induces nerve growth factor and brain-derived neurotrophic factor (Toyomoto et al 2004). In addition, a study by Andreasson's group showed that the DP1 agonist BW245C increases the level of cAMP and protects hippocampal slice cultures against N-methyl-D-aspartic acid (NMDA)-induced excitotoxicity (Liang et al 2005).…”

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confidence: 99%

Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice

Ahmad

Maruyama

et al. 2010

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The cardiovascular complications reported to be associated with cyclooxygenase inhibitor use have shifted our focus toward prostaglandins and their respective receptors. Prostaglandin D 2 and its DP1 receptor have been implicated in various normal and pathologic conditions, but their role in stroke is still poorly defined. Here, we tested whether DP1 deletion aggravates N-methyl-D-aspartic acid (NMDA)-induced acute toxicity and whether DP1 pharmacologic activation protects mice from acute excitotoxicity and transient cerebral ischemia. Moreover, since the elderly are more vulnerable to stroke-related damage than are younger patients, we tested the susceptibility of aged DP1 knockout (DP1 −/− ) mice to brain damage. We found that intrastriatal injection of 15 nmol NMDA caused significantly larger lesion volumes (27.2±6.4%) in young adult DP1 −/− mice than in their wild-type counterparts. Additionally, intracerebroventricular pretreatment of wild-type mice with 10, 25, and 50 nmol of the DP1-selective agonist BW245C significantly attenuated the NMDA-induced lesion size by 19.5± 5.0%, 39.6±7.7%, and 28.9±7.0%, respectively. The lowest tested dose of BW245C also was able to reduce middle cerebral artery occlusion-induced brain infarction size significantly (21.0±5.7%). Interestingly, the aggravated NMDA-induced brain damage was persistent in older DP1 −/− mice as well. We conclude that the DP1 receptor plays an important role in attenuating brain damage and that selective targeting of this receptor could be considered as an adjunct therapeutic tool to minimize stroke damage.

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“…PGs are produced as a result of cyclooxygenase (COX) activity and modulate cerebral blood flow regulation, synaptic transmission, neurotrophin production, angiogenesis, gene expression and can change such biological processes like pain perception, body temperature and sleep/awake cycle (Ahmadi et al, 2002;Kunz et al, 2006;Urade and Hayashi, 1999;Toyomoto et al, 2004;Chen et al, 2002;Chen and Bazan, 2005;Zhu et al, 2006). In addition, many studies have attested to the importance of brain PGs in the development of Alzheimer's disease, stroke, brain inflammation, traumatic brain injury and neurodegenerative diseases Bazan et al, 1995;Minghetti, 2004).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia

et al. 2007

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Prostaglandins (PGs) are bioactive lipid mediators released following brain hypoxic-ischemic injury. Clearance and re-uptake of these prostaglandins occur via a transmembrane prostaglandin transporter (PGT), which exchanges PG for lactate. We used western blot analyses to examine the PGT developmental profile and its regional distribution as well as changes in transporter expression during chronic hypoxia. Microsomal preparations from four brain regions (cortex, hippocampus, cerebellum and brainstem/diencephalon) showed gradual increases in prostaglandin transporter expression in all brain regions examined from postnatal day 1 till day 30. There was a significant regional heterogeneity in the prostaglandin transporter expression with highest expression in the cortex, followed by cerebellum and hippocampus, and least expressed in the brainstem-diencephalon. To further delineate the pattern of prostaglandin transporter expression, separate astrocytic and neuronal microsomal preparations were also examined. In contrast to neurons, which had a robust expression of prostaglandin transporters, astrocytes had very little PGT expression under basal conditions. In response to chronic hypoxia, there was a significant decline in PGT expression in vivo and in neurons in vitro, whereas cultured astrocytes increased their PGT expression. This is the first report on PGT expression in the central nervous system (CNS) and our studies suggest that PGTs have 1) a widespread distribution in the CNS; 2) a gradual increase and a differential expression in various regions during brain development; and 3) striking contrast in expression between glia and neurons, especially in response to hypoxia. Since PGTs play a role as prostaglandin-lactate exchangers, we hypothesize that PGTs are important in the CNS during stress such as hypoxia.

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Prostaglandins are powerful inducers of NGF and BDNF production in mouse astrocyte cultures

Cited by 92 publications

References 36 publications

Added astroglia promote greater synapse density and higher activity in neuronal networks

Added astroglia promote greater synapse density and higher activity in neuronal networks

Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia

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