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

The role of agrin in synaptogenesis has been extensively studied. On the other hand, little is known about the function of this extracellular matrix protein during developmental processes that precede the formation of synapses. Recently, agrin was shown to regulate the rate of neurite elongation and the behavior of growth cones in hippocampal and spinal neurons, respectively. However, the molecular mechanisms underlying these effects have not been completely elucidated. In the present study, we analyzed the morphological and molecular changes induced by agrin in growth cones of hippocampal neurons that developed in culture. Morphometric analysis showed a significant enlargement of growth cones of hippocampal neurons cultured in the presence of agrin. These agrin-induced growth cone changes were accompanied by the formation of loops of microtubules highly enriched in acetylated tubulin and an increase in the content of the microtubule-associated protein (MAP)1B. Together, these data provide further insights into the potential molecular mechanisms underlying the effects of agrin on neurite outgrowth in rat central neurons.

Caspase-3- and calpain-mediated tau cleavage are differentially prevented by estrogen and testosterone in beta-amyloid-treated hippocampal neurons.

A growing body of evidence suggests that the proteolytic cleavage of the microtubule-associated protein tau, the main component of neurofibrillary tangles, might play a role in the molecular mechanisms underlying beta-amyloid (Abeta) -induced neurotoxicity in central neurons. In the present study, we analyzed whether sex hormones could prevent such tau cleavage, and hence, protect rat hippocampal neurons against Abeta toxicity. Our results indicated that estrogen and testosterone prevented caspase-3- and calpain-mediated tau cleavage, respectively. Thus, estrogen decreased the levels of caspase-3-cleaved 50-kDa truncated tau, while testosterone prevented the generation of a calpain-cleaved 17-kDa tau fragment. In addition, our results showed that the decrease in the levels of these tau proteolytic forms was accompanied by an increased cell survival in Abeta-treated neurons. Furthermore, our findings indicated that testosterone was more effective than estrogen in protecting hippocampal neurons against Abeta-induced cell death. Collectively, our data suggest that preventing the decline of estrogen and testosterone associated with normal aging might reduce the susceptibility of central neurons to Abeta-induced toxicity.