Increment of CSF fractalkine-positive microvesicles preceded the spatial memory impairment in amyloid beta neurotoxicity.

Abstract

Fractalkine (CX₃CL₁) is a key chemokine, affects neuronal cell communication and involves in Alzheimer's disease pathogenesis. Microvesicles (MVs) participate in neuronal cells' cross-talk in physiological and pathological states. Microvesicles released in cerebrospinal fluid (CSF) may provide a valuable footprint of brain changes. Little information is available regarding the release of fractalkine-positive MVs (CX₃CL₁⁺ -MVs) in the nervous system. We induced cognitive impairment by bilateral injection of amyloid-beta (Aβ) into the cerebral ventricles. We analyzed the CSF by flow cytometry in two experiments (trained and untrained) to elucidate the presence of CX₃CL₁⁺ -MVs. The hippocampal TNF-α as an inflammatory factor was assessed by immunohistochemistry. The Aβ induced spatial memory impairment after two weeks, verified by a decrease in the escape latency in Morris water maze test. It caused an increase in the anxiety-like behaviors demonstrated by a decrease in entries into the open arms of elevated plus maze test. The Aβ increased the percent of the positive area for TNF-α staining. Histological evaluation of the hippocampus confirmed the tissue injuries. The CSF levels of CX₃CL₁⁺ -MVs, increased 2 and 7days after Aβ injection. The Aβ increased the TNF-α staining and provided an inflammatory context to facilitate the MVs release. The rise of CX₃CL₁⁺ -MVs was transient and subsided after two weeks. Both trained and untrained experiments showed a similar rise pattern of CX₃CL₁⁺ -MVs. Increase of fractalkine-positive microvesicles preceded the cognitive impairment, more studies are required to approve the CX₃CL₁⁺ -MVs as a potential biomarker in the early diagnosis of Alzheimer's disease.