Principal Investigator: Chihiro SATO
Grant Title: Effects of environmental factors on the expression of polysialic acid in brain
Abstract
Schizophrenia, bipolar disorder, autism spectrum disorder and major
depression are well-known mental disorders. To understand and treat
Author’sthese diseases, it is important to focus on disease-related molecules that
Photographare known to be ubiquitous in the brain and to be particularly altered in(Optional)
mental disorders. The polysialic acid (polySia/PSA) chain, which
Size is not
specifically modifies the neuronal cell adhesion molecule (NCAM)
specified.
protein, is known to be aberrantly expressed in mental disorders. So far, I
studied the relationship between the polySia chain and mental disorders,
performing pioneering biochemical analysis of disease-related SNPs of
the polySia synthase ST8SIA2 gene and found that all the disease-related SNPs finally lead to theimpairments of structures and functions of polySia (Sato and Hane 2018; Sato and Kitajima 2019).
As it is important to consider both genetic factors and environmental factors to clarify the causesof mental disorders, I focused on the effects of environmental factors on polySia expression in brain
in this research. I adopted the tail suspension test that exposed mice to acute stress as a negativeenvironmental factor. We also adopted the enriched environment as a positive environmental factor.
We analyzed the polySia expression in five brain regions, olfactory bulb, prefrontal cortex, amygdala,hypothalamus, and hippocampus, by the immunochemical and chemical analyses. Finally, we foundthat a 7-min acute stress led to alterations of the polySia expression brain region-specifically. Inolfactory bulb and prefrontal cortex, the polySia expression was decreased. On the other hand, theenriched environment led to the increased expression of polySia in the same regions. The
mechanism of the decrease of polySia by acute Place (P) X Timing (T)stress was shown to relate with sialidase frommicroglia or astrocyte (Abe et al. 2019).
Therefore, I can conclude that not only genetic
factors but also environmental factors affect thebrain region-specific polySia expression.
Our reaserch clearly demonstrtates that
polySia is expressed in an appropriate time (T)and at appropriate cell types of an appropriate
Fine-tuned polySia contributes to normal brain function
brain region (P), and that the expression ofpolySia can thus be defined by the T and P parapmeters. We could actually determine the T and P
parameters under the normal state. Once normal polySia structures were impaired by genetic (G)and/or environmental factors (E), the T and P parameters changed to the abnormal ones. Thus, it isindicated that we would be able to understand the state of brain by monitoring the T and P
parameters for polySia. In addition, if we could succeed in monitoring the T and P parametersinvasively, we might find out apprioriate G x E factors to lower the risk of disease using theseparameters. In this regard, we are now investigating such GREEN factors other than RED factors for
medical application purposes (Sato 2019).
Genetic factors (G) x Environmental Factors (E)Abnormal

NormalAbnormalEnvironmental Factors (E) X Genetic factors (G)polySia-NCAM

polySia field
Quantity
Quality

Repulsive field
Attractive field

Functional field

Risk of disease

Small and lowNoWidenarrow

NoneWidenarrow

None

Hyper

HypoNoneHighDeathafter birth

Large and highHighLow

Ref.(1)Abe C, Yi Y, Hane M, Kitajima K, Sato C. (2019) Acute stress-induced change in polysialic acid levels mediated bysialidase in mouse brain. Sci Rep. 9, 9950; (2) Sato C, Kitajima K. (2019) Sialic acids in neurology. Adv Carbohydr Chem
Biochem. 76, 1-64; (3) Sato C. (2019) polysialic acids. Trends Glycosci Glycotech. 31, E1-E3.