Cellular Localization Studies Of Aspa Vs

The significance of the expression of NAA in oligodendrocytes assumes added importance in view of the increasing evidence that the NAA/ASPA system plays a major role in the myelin lipid synthesis in the brain. Earlier cell culture studies have shown both the presence and absence of NAA in oligodendrocytes based on the culture conditions.47 Optic nerve transaction experiments have suggested that between 5% and 20% of NAA in developing white matter is derived from proliferating oligodendrocyte progenitor cells.48 We have addressed this issue in the rat brain by immunohistochemistry using polyclonal antibodies against NAA as previously described.23-25

Figure 3 shows the immunohistochemical localization of ASPA and NAA in the rat corpus callosum. ASPA staining was moderate to strong in oligodendrocytes throughout corpus callosum (Fig 3A), whereas NAA immunoreactivity was low in oligodendrocytes (Fig 3B). Strong staining for NAA in neurons, and low levels of staining in mature oligodendrocytes is likely to be related in part to the absence of ASPA activity in neurons, and strong ASPA expression and activity in oligodendrocytes. Based on these results, it is not clear if oligodendrocytes synthesize sufficient NAA for myelin synthesis47, or if they acquire a significant proportion of it by neuronal-glial transfer.34 The key question is whether the acetate derived from NAA is essential for postnatal myelin synthesis, or acts as a secondary lipogenic pathway which contributes acetate, but

Figure 3. ASPA immunoreactivity and NAA immunoreactivity in adult rat corpus callosum (CC). ASPA is strongly expressed in oligodendrocytes in the CC (A), whereas NAA is expressed strongly in neurons (above and below the corpus callosum), but only at low levels in oligodendrocytes in the CC (B).

is not critical for myelin synthesis during CNS maturation. To help answer this question, we looked at brain acetate levels in the ASPA -/- mice used for the lipid synthesis studies described above.

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