Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity in the hippocampus, but the mechanisms involved are not fully understood. The neurotrophin couples synaptic activation to changes in gene expression underlying long term potentiation and short term plasticity. Here we show that BDNF acutely up-regulates GluR1, GluR2, and GluR3 ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits in 7-day tropomyosin-related kinase in vitro cultured hippocampal neurons. The increase in GluR1 and GluR2 protein levels in developing cultures was impaired by K252a, a Trk inhibitor, and by translation (emetine and anisomycin) and transcription (␣-amanitine and actinomycin D) inhibitors. Accordingly, BDNF increased the mRNA levels for GluR1 and GluR2 subunits. Biotinylation studies showed that stimulation with BDNF for 30 min selectively increased the amount of GluR1 associated with the plasma membrane, and this effect was abrogated by emetine. Under the same conditions, BDNF induced GluR1 phosphorylation on Ser-831 through activation of protein kinase C and Ca 2؉ -calmodulin-dependent protein kinase II. Chelation of endogenous extracellular BDNF with TrkB-IgG selectively decreased GluR1 protein levels in 14-day in vitro cultures of hippocampal neurons. Moreover, BDNF promoted synaptic delivery of homomeric GluR1 AMPA receptors in cultured organotypic slices, by a mechanism independent of NMDA receptor activation. Taken together, the results indicate that BDNF up-regulates the protein levels of AMPA receptor subunits in hippocampal neurons and induces the delivery of AMPA receptors to the synapse.Neurotrophins are essential for the development of the vertebrate nervous system, modulate synaptic function, and play an important role in synaptic plasticity (1, 2). Brain-derived neurotrophic factor (BDNF) 3 has been implicated in activitydependent synaptic plasticity, particularly in long term potentiation (LTP) induced by high frequency stimulation. Accordingly, LTP is impaired in the hippocampal CA1 region of animals deficient in BDNF, but it can be rescued by supplying the neurotrophin (3-5). Chelation of endogenous BDNF also prevents the induction of LTP by theta burst stimulation and reduces late phase LTP induced by high frequency stimulation (6, 7). Furthermore, the late phase LTP induced by tetanic stimulation was not observed in slices from BDNF knock-out mice and was also abrogated when TrkB receptors were blocked (8). Taken together, the available evidences point to a direct role of BDNF in the early and late phases of LTP.Binding of BDNF to TrkB receptors is followed by activation of intracellular signaling pathways, including the Ras/extracellular signal-regulated protein kinase, phospholipase C␥ (PLC␥), phosphatidylinositol-3-kinase/Akt, and Src pathways (9 -11). TrkB receptors are located on axon terminals and in the post-synaptic density of glutamatergic synapses (12-14), but whether the effects of BDNF on synaptic plasticity are mediated by pre-and/or post-sy...

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Photoacoustic calorimetry was used to measure the quantum yields of singlet molecular oxygen production by the triplet states of tetraphenylporphyrin (TPP), ZnÀTPP and CuÀTPP in toluene, yielding values of 0.67 AE 0.14, 0.68 AE 0.19 and 0.03 AE 0.01, respectively. We show that a novel dichlorophenyl derivative of Zn À TPP is capable of singlet-oxygen production with a 0.90 AE 0.07 quantum yield. The synthesis and characterisation of a new photostable chlorin with high absorptivity in the red that is capable of singlet-oxygen production with 0.54 AE 0.06 quantum yield is described. Our results suggest that chlorinated chlorins may be interesting new sensitisers for photodynamic therapy.

The neurotrophin brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and function, particularly of the glutamatergic synapses. BDNF may be released in the mature form, which activates preferentially TrkB receptors, or as proBDNF, which is coupled to the stimulation of the p75 NTR . In the mature form BDNF induces rapid effects on glutamate release, and may induce short-and long-term effects on the postsynaptic response to the neurotransmitter. BDNF may affect glutamate receptor activity by inducing the phosphorylation of the receptor subunits, which may also affect the interaction with intracellular proteins and, consequently, their recycling and localization to defined postsynaptic sites. Stimulation of the local protein synthesis and transcription activity account for the delayed effects of BDNF on glutamatergic synaptic strength. Several evidences show impaired synaptic plasticity of glutamatergic synapses in diseases where compromised BDNF function has been observed, such as Huntington's disease, depression, anxiety, and the BDNF polymorphism Val66Met, suggesting that upregulating BDNF-activated pathways may be therapeutically relevant. This review focuses on recent advances in the understanding of the regulation of the glutamatergic synapse by BDNF, and its implications in synaptic plasticity.

The neurotrophin BDNF regulates the activity-dependent modifications of synaptic strength in the CNS. Physiological and biochemical evidences implicate the NMDA glutamate receptor as one of the targets for BDNF modulation. In the present study, we investigated the effect of BDNF on the expression and plasma membrane abundance of NMDA receptor subunits in cultured hippocampal neurons. Acute stimulation of hippocampal neurons with BDNF differentially upregulated the protein levels of the NR1, NR2A and NR2B NMDA receptor subunits, by a mechanism sensitive to transcription and translation inhibitors. Accordingly, BDNF also increased the mRNA levels for NR1, NR2A and NR2B subunits. The neurotrophin NT3 also upregulated the protein levels of NR2A and NR2B subunits, but was without effect on the NR1 subunit. The amount of NR1, NR2A and NR2B proteins associated with the plasma membrane of hippocampal neurons was differentially increased by BDNF stimulation for 30 min or 24 h. The rapid upregulation of plasma membrane-associated NMDA receptor subunits was correlated with an increase in NMDA receptor activity. The results indicate that BDNF increases the abundance of NMDA receptors and their delivery to the plasma membrane, thereby upregulating receptor activity in cultured hippocampal neurons.