Clearance of ß-amyloid and synapses by the optogenetic depolarization of microglia is complement selective.

Microglia actively monitor the neighboring brain microenvironments and constantly contact synapses with their unique ramified processes. In neurodegenerative diseases, including Alzheimer's disease (AD), microglia undergo morphological and functional alterations. Whether the direct manipulation of microglia can selectively or concurrently modulate synaptic function and the response to disease-associated factors remains elusive. Here, we employ optogenetic methods to stimulate microglia in vitro and in vivo. Membrane depolarization rapidly changes microglia morphology and leads to enhanced phagocytosis. We found that the optogenetic stimulation of microglia can efficiently promote ß-amyloid (Aß) clearance in the brain parenchyma, but it can also enhance synapse elimination. Importantly, the inhibition of C1q selectively prevents synapse loss induced by microglia depolarization but does not affect Aß clearance. Our data reveal independent microglia-mediated phagocytosis pathways toward Aß and synapses. Our results also shed light on a synergistic strategy of depolarizing microglia and inhibiting complement functions for the clearance of Aß while sparing synapses.

Probing Anion - π interactions between fluoroarene and carboxylate anion in aqueous solutions.

Despite the much progress in developing π-conjugated fluoroarene moieties based functional materials in which anion - π interactions are commonly involved, it remains challenging to quantitatively characterize the nanomechanical interaction mechanism of these anion - π systems, particularly in aqueous solutions. In this study, we reported the first experimental quantification of the nanomechanics of anion - π interactions between π-conjugated fluoroarene moieties and carboxylate anions in aqueous solutions through direct molecular force measurements, with a special focus on the impact of the anion species, concentration and of the substitution effect of aromatic side group. The results using surface forces apparatus (SFA) and single-molecule force spectroscopy (SMFS) provide complementary evidences to demonstrate that the robust and reversible adhesion measured between the fluoroarene π systems and carboxylate anions was mainly attributed to anion - π interaction. Moreover, their nanomechanical properties were also systematically scrutinized, with the interaction strength being found to be significantly determined by the contact time, the type of fluoroarene systems (PFST > DFST) and the type of anions and ion concentration (HPO42- > CO32- > I- > Cl- ≈ NO3- > F-).