Overactivation of Heme Oxigenase 1 early in life leads to symptoms similar to schizophrenia or Parkinson's disease

Overactivation of Heme Oxigenase 1 (HO-1; HMOX1) early in life leads to symptoms similar to schizophrenia or Parkinson’s disease, depending on how early this was happening (in mice).

Astroglial heme oxygenase-1 (HO-1) overexpression in mice throughout embryogenesis until 6 or 12 months of age resulted in hyperdopaminergia, hyperkinesia/stereotypy ameliorated with clozapine, deficient prepulse inhibition of the acoustic startle response, reduced preference for social novelty, impaired nest building, and cognitive dysfunction reminiscent of SCZ.

On the contrary, astroglial HO-1 overexpression between 8.5 and 19 months of age yielded a PD-like behavioral phenotype with hypodopaminergia, altered gait, locomotor incoordination, and reduced olfaction (R1)

In plain English: presence of factors that overactivate HO-1 early in life leads to neurological and psychiatric disturbances.

HO-1 is one of the target enzymes of Nrf2, so activation of Nrf2 in most cases activates HO-1 (exception is special kind of modification of Nrf2 when HO-1 activation is not required).

Oxidative stress, loss of activity of Thioredoxine Reductases (selenoenzyme), presence of toxic substances that require detoxification lead to HO-1 induction.