Agrin Controls Synaptic Differentiation in Hippocampal Neurons

Abstract

Agrin controls the formation of the neuromuscular junction. Whether it regulates the differentiation of other types of synapses remains unclear. Therefore, we have studied the role of agrin in cultured hippocampal neurons. Synaptogenesis was severely compromised when agrin expression or function was suppressed by antisense oligonucleotides and specific antibodies. The effects of antisense oligonucleotides were found to be highly specific because they were reversed by adding recombinant agrin and could not be detected in cultures from agrin-deficient animals. Interestingly, the few synapses formed in reduced agrin conditions displayed diminished vesicular turnover, despite a normal appearance at the EM level. Thus, our results demonstrate the necessity of agrin for synaptogenesis in hippocampal neurons.

New roles for astrocytes: Regulation of CNS synaptogenesis

“…Finally, there appears to be a link between astrocytes and the most prominent synaptogenic factor, agrin, a motoneuron-derived signal that is essential for the formation of neuromuscular junctions (NMJs) [18] and that might play a role in synaptogenesis in the CNS [49]. Contact with mouse glia reduced levels of mRNA encoding agrin in cultured rat hippocampal neurons, whereas soluble glial factors halved the expression of a specific isoform but left the total level unaffected [50].…”

The Process-inducing Activity of Transmembrane Agrin Requires Follistatin-like Domains

“…1, 2, 6). Although neurons from mice with a targeted deletion of the agrn gene form synaptic specializations in vitro and in vivo (7,8), the acute suppression of agrin expression or function by antisense oligonucleotides or antibodies influences the formation and function of interneuronal synapses (9,10). Likewise, brains of agrin-deficient mice, whose perinatal death was prevented by the re-expression of agrin in motor neurons, have a severely reduced number of pre-and postsynaptic specializations as well as functional deficits at excitatory synapses in the CNS 3 (11).…”

Agrin induced morphological and structural changes in growth cones of cultured hippocampal neurons

“…The results obtained clearly indicated that agrin plays a key role in the formation of neuromuscular junctions by inducing the clustering of the acetylcholine receptors at synaptic sites (reviewed by Bowe and Fallon, 1995;McMahan, 1990;Campanelli et al, 1991;Hall & Sanes, 1993;Haydon & Drapeau, 1995;Magill-Solc and McMahan, 1988;Sanes, 1997). A growing body of evidence suggests that agrin also participates in the formation of interneuronal synapses (Ferreira, 1999;Bose et al, 2000;Mantych and Ferreira, 2001;Tournell et al, 2006).…”