Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment

In the citing paper

“Reactive microglia and brain-infiltrating macrophages impair mechanisms of cellular homeostasis and plasticity such as the ongoing generation of myelin-forming oligodendrocytes (Gibson et al., 2019), myelin plasticity (Geraghty et al., 2019), and new neuron generation in the hippocampus (Monje et al., 2002, 2003, 2007).”

In the citing paper

“Microglia, brain-resident macrophages, become persistently reactive following exposure to certain chemotherapy drugs, after cranial radiation, or after systemic inflammatory challenge with low-dose lipopolysaccharide (Geraghty et al., 2019; Gibson et al., 2019; Monje et al., 2002, 2003, 2007).”

In the citing paper

“A distinct subpopulation of microglia that reside in white matter (Hammond et al., 2019) are selectively activated by systemic insults such as exposure to the chemotherapy drug methotrexate (Gibson et al., 2019).”

In the citing paper

“This complex cellular dysregulation is thought to contribute importantly to cognitive impairment, and anti-inflammatory strategies correct this multicellular dysregulation and rescue cognition in disease states such as those occurring after exposure to neurotoxic cancer therapies (Geraghty et al., 2019; Gibson et al., 2019; Monje et al., 2003) and in aging (Villeda et al., 2011).”

In the citing paper

“This complex cellular dysregulation is thought to contribute importantly to cognitive impairment, and anti-inflammatory strategies correct this multicellular dysregulation and rescue cognition in disease states such as those occurring after exposure to neurotoxic cancer therapies (Geraghty et al., 2019; Gibson et al., 2019; Monje et al., 2003) and in aging (Villeda et al., 2011).”

In the citing paper

“In contrast to methotrexate chemotherapy exposure (Geraghty et al., 2019; Gibson et al., 2019), changes in myelin sheath thickness relative to axon diameter (g ratio) were not conclusively identified in the remaining myelin sheaths after mild respiratory COVID (Figures S7C–S7F).”

In the citing paper

“Such neuroinflammatory changes—particularly white-matter-selective/enriched microglial reactivity—are associated with impaired hippocampal neurogenesis, dysregulation of the oligodendroglial lineage, and myelin loss in other disease contexts (Geraghty et al., 2019; Gibson et al., 2019; Guttenplan et al., 2021; Liddelow et al., 2017; Monje et al., 2003; Villeda et al., 2011).”

In the citing paper

“As occurs after cancer therapies and in other disease states, the microglial reactivity present after mild respiratory SARS-CoV-2 infection may also induce neurotoxic astrocyte reactivity (Liddelow et al., 2017; Gibson et al., 2019; Guttenplan et al., 2021), as well as aberrant microglial pruning of synapses (Hinkle et al., 2019; Hosseini et al., 2018; Vasek et al., 2016).”

In the citing paper

“While methotrexate directly stimulates reactivity of microglia (Gibson et al., 2019),”

In the citing paper

“For example, microglial depletion strategies can restore similar multicellular deficits and rescue impaired cognitive performance in mouse models of CRCI (Acharya et al., 2016; Gibson et al., 2019),”

In the citing paper

“Preclinical studies in disease models that share numerous features with the cellular dysregulation observed here after mild respiratory COVID have identified anti-inflammatory and neuro-regenerative strategies that restore neural plasticity and rescue cognition (Ayoub et al., 2020; Geraghty et al., 2019; Gibson et al., 2019; Monje et al., 2003; Villeda et al., 2011).”