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The olfactory ensheathing (glial) cells (OECs) have been identified to be useful candidate cells to support regeneration after being transplanted into injured fiber tracts of the central nervous system. We investigated by means of immunocytochemistry and freeze-fracturing the morphology and molecular composition of OEC tight junctions in the rat olfactory system. In addition, we tested the hypothesis whether tight junctions and orthogonal arrays of particles (OAPs) which contain the water channel protein aquaporin-4 (AQP4), are mutually exclusive as suggested in previous studies. In OECs, we found neither OAPs nor AQP4, but tight junctions immunoreactive for ZO-1, occludin, and claudin-5, but immunonegative for ZO-2 and claudin-3. To shed more light on the function of OEC tight junctions, we tested the permeability and tight junction composition of blood vessels and fila olfactoria. We found them both, permeable for infused lanthanum nitrate, and to be immunopositive for ZO-1 and claudin-5. The tight junctions of the OECs are discussed to be responsible for micro-compartmentalization within the olfactory fiber tract providing a benefit for axonal growth.

(1) Intranasal administration is a non-invasive and effective way for the delivery of drugs to brain that circumvents the blood-brain barrier. The aims of the study were to test a nasal delivery system for human beta-amyloid (A beta) peptides, to measure the delivery of the peptides to brain regions, and to test their biological activity in rats. (2) A beta(1-42), in the form of a mixture of oligomers, protofibrils, and fibrils was dissolved in a nasal formulation containing hydrophobic, hydrophylic, and mucoadhesive components. The peptide solution was administered intranasally to rats as a single dose or in repeated doses. (3) Nasally injected A beta labeled with the blue fluorescent dye amino-methyl coumarinyl acetic acid (AMCA) could be detected by fluorescent microscopy in the olfactory bulb and frontal cortex. The concentration of the peptide was quantified by fluorescent spectroscopy, and a significant amount of AMCA-A beta peptide could be detected in the olfactory bulb. Unlabeled A beta also reached the olfactory bulb and frontal cortex of rats as evidenced by intense immunostaining. (4) In behavioral experiments, nasal A beta treatment did not affect anxiety levels (open-field test) and short-term memory (Y-maze test), but significantly impaired long-term spatial memory in the Morris water maze. The treatments did not result in A beta immunization. (5) The tested intranasal delivery system could successfully target a bioactive peptide into the central nervous system and provides a basis for developing a non-invasive and cost effective, new model to study amyloid-induced dysfunctions in the brain.

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