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

Abstract

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.

GABAA and GABAB receptor subunit localization on neurochemically identified neurons of the human subthalamic nucleus

“…Nonphosphorylated neurofilament H (SMI32): The monoclonal mouse anti‐SMI‐32 antibody (Covance, Princeton, NJ, cat# SMI‐32R‐100, RRID: AB_509997) identifies two bands at 180 and 200 kDa that merge into a single neurofilament H line on 2D blots of rat brain homogenates (Goldstein, Sternberger, & Sternberger, ) and the same two bands on western blots of human cerebellum homogenates (manufacturer's data sheet). The antibody has been widely used to identify subpopulations of pyramidal neurons in the monkey and human cerebral cortex (Campbell & Morrison, ), as well as neurons of multiple brain regions (Lowe, Faull, Christie, & Waldvogel, ; Lowe et al, ).…”

Creatine as a booster for human brain function. How might it work?

“…This suggests that glial cells may serve as local producers of creatine, which is then accumulated in neurons via SLC6A8. The bulk of brain SLC6A8 appears to be expressed in neurons [17], small amounts in endothelial cells of the blood-brain barrier, but it appears to be absent from astrocytes [18].…”

Mild guanidinoacetate increase under partial guanidinoacetate methyltransferase deficiency strongly affects brain cell development

“…We chose 3D organotypic brain cell cultures to better understand GAMT deficiency in developing CNS (Honegger and Monnet-Tschudi, 2001;Braissant et al, 2002). They are derived from embryonic rat brains, grown in a chemically-defined medium without serum and Cr, develop in a stereotyped fashion (Figure 2A) and express AGAT, GAMT and SLC6A8 as the in vivo CNS (Braissant et al, 2001(Braissant et al, , 2008(Braissant et al, , 2010Tachikawa et al, 2004;Lowe et al, 2014). To generate gene knockdown, we chose AAV vectors, known to cause little pathogenicity, offering many serotypes and cellular tropism and allowing post-mitotic cell transduction (Cearley et al, 2008).…”

“…Unlike microcapillary endothelial cells at blood-brain barrier (BBB), surrounding astrocytes do not express SLC6A8, resulting in low Cr uptake efficiency and forcing the brain to complete its Cr needs by expressing AGAT and GAMT (Braissant et al, 2001;Béard and Braissant, 2010;Tachikawa and Hosoya, 2011;Braissant, 2012;Lowe et al, 2014). Under GAMT deficiency, cerebral Cr comes from periphery and the low BBB-crossing efficiency makes CNS Cr-deficient.…”