For the past fifteen years, Dr. Schipper, who specializes in degenerative neurological diseases of aging, has been examining the influence of the protein heme oxygenase-1 (HO-1) on the development of Alzheimer’s and Parkinson’s diseases. An over-abundance of HO-1 is found in the brains of patients suffering from these disorders and had been linked to the pathologies common to both conditions. About five years ago, his lab at the LDI created a mouse model with elevated levels of human HO-1 in the brain. At around forty-eight weeks of age (roughly middle age), the animals displayed dramatically hyperactive and repetitive behaviours manifested, for example, by running around in circles.
“Although not a feature of either Alzheimer’s or Parkinson’s, which generally diminish motor function,” said Dr. Schipper, “hyperactivity and repetitive behaviour are characteristic of other human neuropsychiatric conditions, including schizophrenia,autism, and attention deficit disorder.”
Closer examination of the model has revealed about a dozen neuropathological and neurochemical abnormalities that are attributes of human schizophrenia, including excessive dopamine levels in appropriate brain regions and decreased levels of the protein reelin, which may be a factor in the abnormal brain development observed in schizophrenia. These additional associations provide further evidence that increased levels of HO-1 in the brain may be a key factor in the development of the disease.
“The indications are that if HO-1 is over-expressed early in life, we observe schizophrenic features, while we see parkinsonian symptoms when it is induced later in life.” said Dr. Schipper. “It is fascinating that the same gene causes opposite outcomes depending on when the gene is expressed in the course of the life cycle. This could suggest that HO-1 acts as a funnel for a variety of stressors which may trigger schizophrenia in early life and Parkinson’s or Alzheimer’s in later life.”
From a clinical perspective, the successful development of a selective HO-1 inhibitor – a project currently underway in Dr. Schipper’s lab – may prove important in blocking this particular pathway to disease and offers a promising, and unexplored, avenue for future research into schizophrenia.
The results of his research, entitled “Schizophrenia-like features in transgenic mice overexpressing human HO-1 in the astrocytic compartment,” appear in the August 8 issue of the Journal of Neuroscience, and can be found at www.jneurosci.org. Dr. Schipper’s co-authors on the paper include Wei Song, Hillel Zukor, Shih-Hsiung Lin, Jacob Hascalovici, Adrienne Liberman, Ayda Tavitian, Jeannie Mui, Hojatollah Vali, Xinkang Tong, Sanjeev Bhardwaj, Lalit Srivastava, and Edith Hamel. A video of the mouse model, illustrating hyperlocomotor activity, is available at www.ladydavis.ca/en/hymanschipper.
For further information, and to arrange interviews, contact:
Tod Hoffman
Research Communications Officer
Lady Davis Institute
Tel.: 514-340-8222 x 8661
Email: thoffman@jgh.mcgill.ca
Source of text: Montreal Jewish General Hospital
