Astrocytic and Neuronal Apolipoprotein E Isoforms Differentially Affect Neuronal Excitability

• DOI: 10.3389/fnins.2021.734001
• Publication Date: 2021-09-21T04:29:51Z
• Authors: Sabine C. Konings; Laura Torres-Garcia; Isak Martinsson; Gunnar K. Gouras
• Keywords: Apolipoprotein E; Premovement neuronal activity

Synaptic changes and neuronal network dysfunction are among the earliest in Alzheimer’s disease (AD). Apolipoprotein E4 (ApoE4), major genetic risk factor AD, has been shown to be present at synapses induce hyperexcitability mouse knock-in brain regions vulnerable AD. ApoE is mainly generated by astrocytes, however, neurons can also produce under stress conditions such as aging. The potential synaptic function(s) of whether cellular source might affect excitability remain poorly understood. Therefore, aim this study was elucidate localization effects on activity two main human isoforms from different sources control AD-like vitro cultured neuron models. In seen localize or near terminals. Additionally, we detected a source-specific effect measured live cell Ca 2+ imaging. Neuronal increases after acute but not long-term administration ApoE4 astrocyte medium. contrast, expressed appears highest firing rate presence ApoE3, rather than ApoE4. Moreover, increased APP/PS1 AD transgenic compared wild-type absence astrocytic ApoE4, ApoE3. summary, target differentially depending produced astrocytes neurons. Astrocytic induces strongest with while most active efficient induced caused