| First Author | Goldberg AR | Year | 2025 |
| Journal | Neuron | Volume | 113 |
| Issue | 6 | Pages | 858-875.e10 |
| PubMed ID | 39837324 | Mgi Jnum | J:366407 |
| Mgi Id | MGI:7863088 | Doi | 10.1016/j.neuron.2024.12.026 |
| Citation | Goldberg AR, et al. (2025) Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition. Neuron |
| abstractText | Gliomas are aggressive neoplasms that diffusely infiltrate the brain and cause neurological symptoms, including cognitive deficits and seizures. Increased mTOR signaling has been implicated in glioma-induced neuronal hyperexcitability, but the molecular and functional consequences have not been identified. Here, we show three types of changes in tumor-associated neurons: (1) downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development and upregulation of cytoskeletal transcripts via neuron-specific profiling of ribosome-bound mRNA, (2) marked decreases in dendritic spine density via light and electron microscopy, and (3) progressive functional alterations leading to neuronal hyperexcitability via in vivo calcium imaging. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed these tumor-induced changes. These findings reveal mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma and suggest new strategies for treating glioma-associated neurological symptoms. |
