Skip to main content
. 2005 Nov 23;25(47):10884–10893. doi: 10.1523/JNEUROSCI.2909-05.2005

Figure 6.

Figure 6.

Role of megalin in choroid plexus. A, HIV-directed expression of miniMegalin (miniMeg) in choroid plexus of old rats results in increased megalin levels 6 months after injection, compared with HIV-injected controls. Representative blot is shown (n=4). B, Old rats have decreased megalin content in choroid plexus compared with adult animals. Representative blot and quantitation histograms. **p< 0.01 versus adult rats by Student's ttest (n=4). Error bars represent SEM. C, Hpf-tau deposits (red) within the pyramidal cell layer of the hippocampus in different rodent models of cognitive deterioration after modulation of mega lin levels in choroid plexus. Neurons are stained with calbindin (green). Ca,Cb, Hpf-tau staining, readily detectable in aged rats (30 months of age), is less prominent in aged rats expressing miniMeg in choroid plexus for 6 months. The left inset shows magnification of deposits in Ca. Cc, Cf, Ci, Scattered Hpf-tau deposits in APP/PS1 mice become more apparent after reduction of megalin levels with siMeg (Cf), whereas they are not substantially modified after miniMeg expression (Ci). The right inset shows magnification of deposits inCf. Cd, Ce, LID mice have low levels of Hpf-tau deposits that disappear after miniMeg expression for 3 months. The right inset shows magnification of small deposits in Cd. Cg, Ch, Injection of HIV-siMeg to adult rats resulted in the appearance of scattered Hpf-tau deposits in the hippocampus. The inset in Ch shows magnification of the deposits. Representative hippocampal sections are shown. Changes in Hpf-tau levels were quantified by Western blot (see Results). Control animals received void HIV vector intracerebroventricular injections in all cases. Scale bar, 20 μm. min Meg, miniMegalin; siMeg, siMegalin. D, Functional interactions between serum IGF-I and choroid plexus megalin. Serum IGF-I stimulates its receptor at epithelial choroid plexus cells to induce its own transport across the cell via megalin. Serum IGF-I also enhances transport by megalin of Aβ complexed with its carriers from the CSF to the blood through a caveolin-dependent endocytic pathway involving IGF-I-induced decoupling of Dab2 to megalin. IGF-I requires PKC activity, both to favor transport of Aβ/carrier complexes as well as to be transported itself by megalin. Whether megalin binds IGF-I bound to the IGF-I receptor or free IGF-I requires additional analysis.