Expression patterns of the organic cation/carnitine transporter family in adult murine brain.
Organic cation/carnitine transporters transport carnitine, drugs, and xenobiotics (e.g. choline, acetylcarnitine, betaine, valproic acid), and are expressed in muscle, heart, blood vessels, kidney, gut, etc.


OBJECTIVE
To characterize expression patterns of mOctn1, -2 and -3 in murine brain.


METHODS
We applied our transporter-specific antibodies to mOctn1, -2 and -3, followed by 2 0 antibody and DAB peroxidase detection to serial adult murine brain sections counterstained with hematoxylin.


RESULTS
All three transporters showed strong expression in the external plexiform layer of the olfactory bulb and in olfactory nerve, the molecular layer and neuronal processes of input fibres extending vertically in motor cortex, in the dendritic arborization of the cornu ammonis and dendate gyrus (hippocampus), neuronal processes in the arcuate nucleus (hypothalamus), choroid plexus cells, and neuronal cell bodies and dendrites of cranial nerve nuclei V and VII. In the cerebellum, all three transporters were strongly expressed in dendritic processes of Purkinje cells, but Octn1 and -2 were expressed more strongly than Octn3 in Purkinje cell bodies. In spinal cord, Octn1, -2 and -3 were prominent in axons and dendritic end-arborizations of spinal cord neurons in both ascending and descending white matter tracts, whereas Octn3 was also strongly expressed in grey matter, specifically in anterior horn cell bodies. Octn3 was weakly expressed in glomerular layer neuronal cell bodies of olfactory bulb.


CONCLUSIONS
hOCTN2 deficiency presents with carnitine-responsive cardiomyopathy, myopathy and hypoglycemic, hypoketotic coma with strokes, seizures and delays. In mouse, Octn1, -2 and -3 are expressed in many regions throughout the central nervous system with a pattern suggestive of roles in modulating cerebral bioenergetics and in acetylcholine generation for neurotransmission in olfactory, satiety, limbic, memory, motor and sensory functions. This distribution may play a role in the pattern of neurological injury that occurs in hOCTN2 deficiency during catabolic episodes of hypoglycemic, hypoketotic encephalopathy and which may manifest with cognitive impairment, hypotonia and seizures.
Lamhonwah
Anne Marie
AM
Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, University of Toronto, Toronto, Ont., Canada M5G 1X8.
Hawkins
Cynthia E
CE
Tam
Carolyn
C
Wong
Jeannie
J
Mai
Lydia
L
Tein
Ingrid
I
D000109:Acetylcholine / Q000096:biosynthesis; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000378:metabolism / Q000503:physiopathology; D001931:Brain Mapping; D002331:Carnitine / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002412:Cations / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000172:deficiency* / Q000378:metabolism*; D000074058:Solute Carrier Family 22 Member 5; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism; D027981:Symporters
D002352:Carrier Proteins; D002412:Cations; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C498687:Slc22a21 protein, mouse; C491659:Slc22a4 protein, mouse; C492019:Slc22a5 protein, mouse; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D000109:Acetylcholine; D002331:Carnitine