Distribution of the creatine transporter throughout the human brain reveals a spectrum of creatine transporter immunoreactivity.

Creatine is a molecule that supports energy metabolism in cells. It is carried across the plasma membrane by the creatine transporter. There has been recent interest in creatine for its neuroprotective effects in neurodegenerative diseases and its potential as a therapeutic agent. This study represents the first systematic investigation of the distribution of the creatine transporter in the human brain. We have used immunohistochemical techniques to map out its location and the intensity of staining. The transporter was found to be strongly expressed, especially in the large projection neurons of the brain and spinal cord. These include the pyramidal neurons in the cerebral cortex, Purkinje cells in the cerebellar cortex, and motor neurons of the somatic motor and visceromotor cranial nerve nuclei and the ventral horn of the spinal cord. Many other neurons in the brain also had some degree of creatine transporter immunoreactivity. By contrast, the medium spiny neurons of the striatum and the catecholaminergic neurons of the substantia nigra and locus coeruleus, which are implicated in neurodegenerative diseases, showed a very low to almost absent level of immunoreactivity for the transporter. We propose that the distribution may reflect the energy consumption by different cell types and that the extent of creatine transporter expression is proportional to the cell's energy requirements. Furthermore, the distribution indicates that supplemented creatine would be widely taken up by brain cells, although possibly less by those cells that degenerate in Huntington's and Parkinson's diseases.

Dissociated expression of mitochondrial and cytosolic creatine kinases in the human brain: a new perspective on the role of creatine in brain energy metabolism.

The phosphocreatine/creatine kinase (PCr/CK) system in the brain is defined by the expression of two CK isozymes: the cytosolic brain-type CK (BCK) and the ubiquitous mitochondrial CK (uMtCK). The system plays an important role in supporting cellular energy metabolism by buffering adenosine triphosphate (ATP) consumption and improving the flux of high-energy phosphoryls around the cell. This system is well defined in muscle tissue, but there have been few detailed studies of this system in the brain, especially in humans. Creatine is known to be important for neurologic function, and its loss from the brain during development can lead to mental retardation. This study provides the first detailed immunohistochemical study of the expression pattern of BCK and uMtCK in the human brain. A strikingly dissociated pattern of expression was found: uMtCK was found to be ubiquitously and exclusively expressed in neuronal populations, whereas BCK was dominantly expressed in astrocytes, with a low and selective expression in neurons. This pattern indicates that the two CK isozymes are not widely coexpressed in the human brain, but rather are selectively expressed depending on the cell type. These results suggest that the brain cells may use only certain properties of the PCr/CK system depending on their energetic requirements.