Neuroprotection by pigment epithelial‐derived factor against glutamate toxicity in developing primary hippocampal neurons

Abstract

Pigment epithelial-derived factor (PEDF) has been shown to be a survival factor for cerebellar granule neurons. Here we investigated the ability of PEDF to enhance the survival of hippocampal neurons in culture, and to protect these neurons against acute glutamate toxicity. Hippocampal neurons prepared from 1- to 3-day postnatal rat brain were cultured for either 7 or 14 days in vitro (DIV). At 14 DIV, neurons were only slightly protected (13% +/- 4%) against 50 microM glutamate toxicity when treated with 1 microg/ml of PEDF for 3 successive days before glutamate exposure as measured by lactate dehydrogenase (LDH) release. In comparison, basic fibroblast growth factor (bFGF) at 10 ng/ml for the same treatment period protected 58% +/- 8% of the neurons against glutamate. Using quantitative image analysis of digitized micrographs, we found that the average size of neurons in young, developing hippocampal cultures (7 DIV), was greatly decreased by treatment with 50 microM glutamate. Treatment for up to 5 successive days with 1 microg/ml of PEDF before glutamate addition dramatically increased the average hippocampal neuron soma size, compared to cells treated with glutamate alone. Thus, PEDF may promote the growth of hippocampal neurons, and, if added to developing hippocampal neurons, can also protect these cells from subsequent injury, such as the excitotoxicity of glutamate.

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

“…Others report that in vivo, 0.001 lg/lL is required to protect RGC from excitotoxicity and serum withdrawal, 36 a concentration of PEDF that is also neuroprotective for photoreceptors, cerebellar granule cells, and hippocampal neurons. 9,38,68 After ON transection in vivo, 1 lg/lL intravitreal PEDF and combined cAMPþPEDF treatment promoted 55% RGC survival, similar to the levels of neuroprotection seen after grafting peripheral nerves onto the cut end of the ON, combined with intraocular injections of cAMPþCNTF. Our results suggest that PEDF alone may trigger neuroprotective pathways activated by combined cAMPþCNTF, since combined cAMPþPEDF did not potentiate RGC protection and CNTF delivery on its own did not rescue more than 43% of RGC from death.…”

“…CNTFþcAMP also promotes longer RGC neurite outgrowth than CNTF alone. 68 Thus, although CNTF and PEDF act singly as initiators and elongators of neurite outgrowth, 75,76 their effects become synergistic when each factor is administered in combination with cAMP. Both extrinsic and intrinsic mechanisms regulate axon sprouting and elongation and are often signalled by the same molecules.…”

Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats

“…23,24 PEDF binds to the glycosaminoglycans of the interphotoreceptor matrix, placing it in a prime physical location to affect the underlying neural retina. 25,26 PEDF functions as a survival factor for cultured cerebellar granule cells, [27][28][29] spinal motor neurons, 30,31 and hippocampal neurons 32 in vitro and delays the death of photoreceptor cells in the rd mouse in vivo. 33 In addition to its neurotrophic action, PEDF is antiangiogenic, inducing endothelial apoptosis via the Fas-Fas ligand system.…”

Análise dos mecanismos de neuroplasticidade na porção lombar da medula espinal do rato submetida à lesão isquêmica fototrombótica e tratada pela injeção local de PEDF

“…No final dos anos 90, as atividades anti-angiogênica e de restrição do edema pelo PEDF foram descritas (Dawson et al, 1999) (Taniwaki et al, 1997;Bilak et al, 1999a;DeCoster et al, 1999).…”

“…O aumento da laminina é um sinal de angiogênese local, e a diminuição de sua expressão nos ratos que receberam o tratamento com o PEDF, em relação ao grupo Salina, indica uma ação anti-angiogênica desse fator neurotrófico. Este efeito do PEDF sobre a medula lesada pode interferir indiretamente com as respostas neuroplásticas do órgão, visto sua capacidade de modificar a manutenção neuronal (DeCoster et al, 1999).…”