Secreted Semaphorins Modulate Synaptic Transmission in the Adult Hippocampus

Sahay, Amar; Kim, Chong Hyun; Sepkuty, Jehuda P.; Cho, Edward H.; Huganir, Richard L.; Ginty, David D.; Kolodkin, Alex L.

doi:10.1523/jneurosci.5255-04.2005

Cited by 138 publications

(150 citation statements)

References 47 publications

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“…Next, we determined patterns of hippocampal expression of neuropilin-1 (Nrp1) and neuropilin-2 (Nrp2). Corroborating previous results (18), DG granule cells were found to be positive for both neuropilins (Fig. S2 C and D).…”

Section: Vegf Is Constitutively Expressed In Astrocytes Of the Adultsupporting

confidence: 91%

Reversible modulations of neuronal plasticity by VEGF

Licht

Goshen

Avital

et al. 2011

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

225

191

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Neurons, astrocytes, and blood vessels are organized in functional “neurovascular units” in which the vasculature can impact neuronal activity and, in turn, dynamically adjust to its change. Here we explored different mechanisms by which VEGF, a pleiotropic factor known to possess multiple activities vis-à-vis blood vessels and neurons, may affect adult neurogenesis and cognition. Conditional transgenic systems were used to reversibly overexpress VEGF or block endogenous VEGF in the hippocampus of adult mice. Importantly, this was done in settings that allowed the uncoupling of VEGF-promoted angiogenesis, neurogenesis, and memory. VEGF overexpression was found to augment all three processes, whereas VEGF blockade impaired memory without reducing hippocampal perfusion or neurogenesis. Pertinent to the general debate regarding the relative contribution of adult neurogenesis to memory, we found that memory gain by VEGF overexpression and memory impairment by VEGF blockade were already evident at early time points at which newly added neurons could not yet have become functional. Surprisingly, VEGF induction markedly increased in vivo long-term potentiation (LTP) responses in the dentate gyrus, and VEGF blockade completely abrogated LTP. Switching off ectopic VEGF production resulted in a return to a normal memory and LTP, indicating that ongoing VEGF is required to maintain increased plasticity. In summary, the study not only uncovered a surprising role for VEGF in neuronal plasticity, but also suggests that improved memory by VEGF is primarily a result of increasing plasticity of mature neurons rather than the contribution of newly added hippocampal neurons.

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Section: Vegf Is Constitutively Expressed In Astrocytes Of the Adultsupporting

confidence: 91%

Reversible modulations of neuronal plasticity by VEGF

Licht

Goshen

Avital

et al. 2011

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

225

191

View full text Add to dashboard Cite

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“…In another model, during the process of electrically induced epileptogenesis in rats, a transient reduction in Sema3A expression was described and correlated to mossy fibre sprouting believed to have a critical function in the hyperexcitability of the hippocampus in temporal lobe epilepsy of patients (Holtmaat et al, 2003). Direct functional evidence for a function of semaphorins and their receptors in epilepsy is supported by Sema3F knockout mice (Sahay et al, 2005) and some NRP2 mutant mice (Giger et al, 2000;Chen et al, 2000) that are more prone to seizures. Therefore, we cannot consider resection pieces of epileptic patients as control for normal tissue.…”

Section: Discussionmentioning

confidence: 98%

Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

et al. 2008

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Gliomas are characterised by local infiltration, migration of tumour cells across long distances and sustained angiogenesis; therefore, proteins involved in these processes are most likely important. Such candidates are semaphorins involved in axon guidance and cell migration. In addition, semaphorins regulate tumour progression and angiogenesis. For cell signalling, class-4 semaphorins bind directly to plexins, whereas class-3 semaphorins require additional neuropilin (NRP) receptors that also bind VEGF 165 . The anti-angiogenic activity of class-3 semaphorins can be explained by competition with VEGF 165 for NRP binding. In this study, we analysed the expressions of seven semaphorins of class-3, SEMA4D, VEGF and the NRP1 and NRP2 receptors in 38 adult glial tumours. In these tumours, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival. In addition, SEMA3D expression was reduced in high-grade as compared with low-grade gliomas. In contrast, VEGF correlated with higher grade and poor survival. Thus, our data suggest a function for a subset of class-3 semaphorins as inhibitors of tumour progression, and the prognostic value of the VEGF/SEMA3 balance in adult gliomas. Moreover, in multivariate analysis, SEMA3G was found to be the only significant prognostic marker.

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“…First, mice deficient for Sema3F, neuropilin-2, or plexinA3 show defects in axonal pruning of postnatal hippocampal projections (Bagri et al, 2003;Chen et al, 2000Chen et al, , 2001Giger et al, 2000;Sahay et al, 2003). Second, Sema3s act as modulators of synaptic transmission in postnatal hippocampal slice cultures (Sahay et al, 2005). Similar to Sema3s and their receptors, MICALs are persistently and strongly expressed in the postnatal and adult nervous system.…”

Section: Micals Are Expressed In the Intact And Injured Nervous Systemmentioning

confidence: 99%