Rat retinal ganglion cells co-express brain derived neurotrophic factor (BDNF) and its receptor TrkB

Vecino, Elena; Garcı́a-Grespo, David; Garcı́a, Mónica; Martínez‐Millán, Luis; Sharma, S. C.; Carrascal, Eliseo

doi:10.1016/s0042-6989(01)00251-6

Cited by 91 publications

(65 citation statements)

References 26 publications

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“…1998). In samples of 22 whole-mounted retinas, the average density of labeled RGCs was 3214 ± 685 cells/mm 2 , comparable to previous measures obtained with other retrograde tracers in rat retina (2116-2725 cells/mm 2 : Linden and Perry, 1983;Villegas-Perez et al, 1988;Vecino et al, 2002) that labeled ~90% of the ganglion cell population (Linden and Perry, 1983). The primary dendrites of CTB-labeled RGC clearly extended into the IPL and their higher-order branches and distal dendrites formed two bands in the IPL (Figure 2B, D).…”

Section: Identification Of Rgc Processessupporting

confidence: 86%

Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina

Zhang

Diamond

2006

J of Comparative Neurology

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At most excitatory synapses, AMPA and NMDA receptors (AMPARs and NMDARs) occupy the postsynaptic density (PSD) and contribute to miniature excitatory postsynaptic currents (mEPSCs) elicited by single transmitter quanta. Juxtaposition of AMPARs and NMDARs may be crucial for certain types of synaptic plasticity, although extrasynaptic NMDARs also may contribute. AMPARs and NMDARs also contribute to evoked EPSCs in retinal ganglion cells (RGCs), but mEPSCs are mediated solely by AMPARs. Previous work indicates that an NMDAR component emerges in mEPSCs when glutamate uptake is reduced, suggesting that NMDARs are located near the release site but perhaps not directly beneath in the PSD. Consistent with this idea, NMDARs on RGCs encounter a lower glutamate concentration during synaptic transmission than do AMPARs. To understand better the roles of NMDARs in RGC function, we have used immunohistochemical and electron microscopic techniques to determine the precise subsynaptic localization of NMDARs in RGC dendrites. RGC dendrites were labeled retrogradely with cholera toxin B subunit (CTB) injected into the superior colliculus (SC) and identified using postembedding immunogold methods. Co-labeling with antibodies directed toward AMPARs and/ or NMDARs, we found that nearly all AMPARs are located within the PSD, while most NMDARs are located perisynaptically, 100-300 nm from the PSD. This morphological evidence for exclusively perisynaptic NMDARs localizations suggests a distinct role for NMDARs in RGC function.

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Section: Identification Of Rgc Processessupporting

confidence: 86%

Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina

Zhang

Diamond

2006

J of Comparative Neurology

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“…Many RGC studies have relied on retrograde labeling (Schuettauf et al, 2002;Vecino et al, 2002;Danias et al, 2003) to study and quantify this heterogeneous, specialized population of retinal neurons. FluoroGold has been the tracer of choice for such studies, and this method requires active transport mechanisms to move endocytic vesicles packed with FG back to the RGC soma (Koebbert et al, 2000); hence, FG and similar tracers do not accumulate in ganglion cells with compromised axon transport.…”

Section: Discussionmentioning

confidence: 99%

Progressive Ganglion Cell Degeneration Precedes Neuronal Loss in a Mouse Model of Glaucoma

Buckingham¹,

Inman²,

Lambert³

et al. 2008

J. Neurosci.

372

336

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Glaucoma is characterized by retinal ganglion cell (RGC) pathology and a progressive loss of vision. Previous studies suggest RGC death is responsible for vision loss in glaucoma, yet evidence from other neurodegenerative diseases suggests axonal degeneration, in the absence of neuronal loss, can significantly affect neuronal function. To characterize RGC degeneration in the DBA/2 mouse model of glaucoma, we quantified RGCs in mice of various ages using neuronal-specific nuclear protein (NeuN) immunolabeling, retrograde labeling, and optic nerve axon counts. Surprisingly, the number of NeuN-labeled RGCs did not decline significantly until 18 months of age, at which time a significant decrease in RGC somal size was also observed. Axon dysfunction and degeneration occurred before loss of NeuN-positive RGCs, because significant declines in RGC number assayed by retrograde tracers and axon counts were observed at 13 months. To examine whether axonal dysfunction/degeneration affected gene expression in RGC axons or somas, NeuN and neurofilament-heavy (NF-H) immunolabeling was performed along with quantitative reverse transcription-PCR for RGC-specific genes in retinas of aged DBA/2 mice. Although these mice had similar numbers of NeuN-positive RGCs, the expression of neurofilament light, Brn-3b, and Sncg mRNA varied; this variation in RGC-specific gene expression was correlated with the appearance of NF-H immunoreactive RGC axons. Together, these data support a progression of RGC degeneration in this model of glaucoma, beginning with loss of retrograde label, where axon dysfunction and degeneration precede neuronal loss. This progression of degeneration suggests a need to examine the RGC axon as a locus of pathology in glaucoma.

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“…BDNF and its receptor TrkB play an important role in the neuroprotection of retinal ganglion cells, which express both BDNF and its receptor TrkB (22). To explore whether NAS could activate endogenous TrkB in the absence of BDNF, BDNF forebrain conditional knockout mice, which lack cortical, hippocampal, and retinal BDNF, were injected intraperitoneally with NAS or melatonin.…”

Section: Nas But Not Other Serotonin Metabolites Induces Trkb Activmentioning

confidence: 99%

N -acetylserotonin activates TrkB receptor in a circadian rhythm

Jang

Liu

Sompol

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

178

166

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Brain-derived neurotrophic factor (BDNF) is a cognate ligand for the TrkB receptor. BDNF and serotonin often function in a cooperative manner to regulate neuronal plasticity, neurogenesis, and neuronal survival. Here we show that NAS (N-acetylserotonin) swiftly activates TrkB in a circadian manner and exhibits antidepressant effect in a TrkB-dependent manner. NAS, a precursor of melatonin, is acetylated from serotonin by AANAT (arylalkylamine Nacetyltransferase). NAS rapidly activates TrkB, but not TrkA or TrkC, in a neurotrophin-and MT3 receptor-independent manner. Administration of NAS activates TrkB in BDNF knockout mice. Furthermore, NAS, but not melatonin, displays a robust antidepressant-like behavioral effect in a TrkB-dependent way. Endogenous TrkB is activated in wild-type C3H/f +/+ mice but not in AANAT-mutated C57BL/ 6J mice, in a circadian rhythm; TrkB activation is high at night in the dark and low during the day. Hence, our findings support that NAS is more than a melatonin precursor, and that it can potently activate TrkB receptor.B rain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which includes nerve growth factor, NT-3, NT-4, and NT-5 (1). BDNF binding to TrkB triggers its dimerization through conformational changes and autophosphorylation of tyrosine residues in its intracellular domain, leading to activation of the three major downstream signaling cascades including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase, and phospholipase C-γ1 (2, 3). Through these pathways, BDNF mediates a variety of neuronal activities involved in neuronal survival, neurogenesis, synaptic plasticity, and so forth, and is implicated in numerous neurological diseases. For instance, loss of BDNF plays a major role in the pathophysiology of depression, and its restoration that induces neuroplastic changes may underlie the action of antidepressant efficacy (4-7).Daily rhythms in indole metabolism are a unique characteristic of the pineal gland. Pineal serotonin (5-HT) levels are higher during the day than at night. Conversely, pineal N-acetylserotonin (NAS) and melatonin levels are low during the day and high at night (8). The switch between day and night profiles of pineal indoles is predominantly regulated by the activity of arylalkylamine N-acetyltransferase (AANAT), which escalates at night 10-to 100-fold (9). AANAT metabolizes serotonin into NAS. AANAT mRNA is prominently expressed in the pineal gland and retina, and weakly in other regions of brain (10-12). NAS is mainly synthesized in the pineal gland, and is subsequently methylated by hydroxyindole-O-methyltransferase to synthesize melatonin. Until recently, NAS was considered only as the precursor of melatonin in the process of melatonin biosynthesis from serotonin. Melatonin is highly lipophilic and is not stored at significant levels. Accordingly, it is released into the blood immediately upon synthesis. Melatonin's role in the regulation of circadian rhythms and other functions is mediated primarily by me...

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Rat retinal ganglion cells co-express brain derived neurotrophic factor (BDNF) and its receptor TrkB

Cited by 91 publications

References 26 publications

Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina

Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina

Progressive Ganglion Cell Degeneration Precedes Neuronal Loss in a Mouse Model of Glaucoma

N -acetylserotonin activates TrkB receptor in a circadian rhythm

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