Reduced levels of NGF shift astrocytes toward a neurotoxic phenotype

• DOI: 10.3389/fcell.2023.1165125
• Publication Date: 2023-04-18T05:49:54Z
• Authors: Alexia Tiberi; Nicola Maria Carucci; Giovanna Testa; Caterina Rizzi; Paola Pacifico; Giulia Borgonovo; Ivan Arisi; Mara D’Onofrio; Rossella Brandi; Wen-Biao Gan; Simona Capsoni; Antonino Cattaneo
• Keywords: NGF; Cell and Developmental Biology; calcium; astrocytes; calcium; co-cultures; neurotoxicity; neurotrophins; NGF; reactive astrocytes; co-cultures; reactive astrocytes; QH301-705.5; astrocytes, NGF, calcium, co-cultures, reactive astrocytes, neurotrophins, neurotoxicity; astrocytes; Biology (General); NGF; astrocytes; calcium; co-cultures; neurotoxicity; neurotrophins; reactive astrocytes; neurotrophins

Nerve growth factor (NGF) is critical for neuronal physiology during development and adulthood. Despite the well-recognized effect of NGF on neurons, less known about whether can actually affect other cell types in central nervous system (CNS). In this work, we show that astrocytes are susceptible to changes ambient levels NGF. First, observe interfering with signaling vivo via constitutive expression an antiNGF antibody induces astrocytic atrophy. A similar asthenic phenotype encountered uncleavable proNGF transgenic mouse model (TgproNGF#72), effectively increasing brain levels. To examine cell-autonomous, cultured wild-type primary presence antibodies, uncovering a short incubation period sufficient potently rapidly trigger calcium oscillations. Acute induction oscillations by antibodies followed progressive morphological those observed AD11 mice. Conversely, mature has no either activity nor morphology. At longer timescales, transcriptomic analysis revealed NGF-deprived acquire proinflammatory profile. particular, antiNGF-treated upregulation neurotoxic transcripts downregulation neuroprotective mRNAs. Consistent data, culturing neurons leads death. Finally, report both awake anesthetized mice, layer I motor cortex respond increase acute inhibition using NGF-neutralizing or TrkA-Fc scavenger. Moreover, imaging 5xFAD neurodegeneration shows increased level spontaneous astrocytes, which significantly reduced after administration conclusion, unveil novel mechanism driven triggered their sensing reacting