Valproic Acid and Schizophrenia in Mice

Prophylactic Valproic Acid Treatment Prevents Schizophrenia-Related Behaviour in Disc1-L100P Mutant Mice.

Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario, Canada.



Schizophrenia is a neurodevelopmental disorder with onset early in adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptibility gene for schizophrenia and other psychiatric disorders. Disc1-L100P mutant mice show behaviors relevant to schizophrenia at 12 weeks, but not at 8 weeks of age, and may be useful for investigating the onset of schizophrenia in early adulthood.


We investigated whether early valproic acid treatment would prevent behavioral, cellular and gene expression abnormalities in Disc1-L100P mutants.


Valproic acid prevented hyperactivity and deficits in prepulse inhibition and latent inhibition in Disc1-L100P mice.

Genome-wide transcription profiling identified Lcn2 (lipocalin2) transcripts as being elevated by the Disc1 mutation and corrected by valproate.

Disc1-L100P mice also had increased glial cell numbers in the subventricular zone, which was normalized by valproate. Genetic deletion of Lcn2 normalized glial cell numbers and behavior in Disc1-L100P mutants.


Pharmacological treatments are a feasible way of preventing abnormal behaviour in a genetic model of schizophrenia. Lcn2 is a potential novel drug target for early intervention in schizophrenia.


Interesting Readings

Valproic acid (VPA), an acidic chemical compound, has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia.

Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism.

Animal model of autism induced by prenatal exposure to valproate: Altered glutamate metabolism in the hippocampus.

This entry was posted in Autism, co-morbid, Depression, Environment, Neurology, Physiology, Schizophrenia, Treatment and tagged , , , , . Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s