Effect of age onset on schizophrenia-like phenotypes and underlying mechanisms in model mice

Area of Science:

• Neuroscience
• Psychiatry
• Cellular Biology

Background:

• Schizophrenia presents differently based on age of onset in humans.
• Distinct phenotypes and cellular mechanisms may underlie early-onset schizophrenia (EOS) and late-onset schizophrenia (LOS).

Purpose of the Study:

• To investigate age-dependent differences in schizophrenia model mice.
• To compare behavioral and cellular phenotypes between adolescent- and adult-onset schizophrenia models.

Main Methods:

• Nrg1 signaling was altered in adolescent and adult mice using anti-Nrg1 antibodies.
• Behavioral tests assessed phenotypes like hyperlocomotion, working memory, and fear conditioning.
• In vitro electrophysiology examined neuronal excitability and synaptic function.

Main Results:

• Both EOS- and LOS-like mice exhibited shared behaviors: hyperlocomotion, impaired working memory, and fear conditioning.
• EOS-like mice showed enhanced synaptic excitation (altered excitation/inhibition balance).
• LOS-like mice displayed elevated intrinsic excitability in fast-spiking GABAergic neurons.

Conclusions:

• Schizophrenia-like phenotypes are largely conserved across age-onset models.
• Distinct cellular mechanisms differentiate EOS and LOS models, particularly in neuronal excitability and synaptic function.
• These age-specific cellular differences are crucial for targeted diagnosis and treatment strategies in schizophrenia.