Oligodendroglial dysfunction drives parvalbumin interneuron hypomyelination, circuit dysfunction and social deficits in an ASD model

In the cntnap2-/- mouse model of ASD, transiently impaired OPC differentiation delays myelination in somatosensory cortex and corpus callosum, producing PV interneuron hypomyelination and social deficits.

• Why it matters: Autism-linked circuit development is associated with abnormal myelination, but the developmental timing and how oligodendroglial dysfunction translates into PV interneuron and behavior changes are unclear.
• What they did: The study used cntnap2-/- mice to assess early postnatal OPC differentiation, myelin lipid composition, sheath wrapping, microgliosis, oligodendrocyte apoptosis, and oligodendrocyte transcriptomic shifts, then tested early clemastine or pranlukast treatment.
• The result: Promyelinating agents clemastine or pranlukast restored OPC differentiation, myelination, and PV maturation, rescued circuit dysfunction including excitation/inhibition balance and gamma oscillations, and ameliorated social deficits and behavioural inflexibility.

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