Expression and Distribution of Cystic Fibrosis Transmembrane Conductance Regulator in Neurons of the Human Brain

Abstract

The importance of the molecule cystic fibrosis transmembrane conductance regulator (CFTR) is reflected in the many physiological functions it regulates. It is known to be present in epithelial cells of the lungs, pancreas, sweat glands, gut, and other tissues, and gene mutations of CFTR cause cystic fibrosis (CF). We studied the expression and distribution of CFTR in the human brain with reverse transcriptase polymerase chain reaction, in situ hybridization, and immunohistochemistry. This study demonstrates widespread and abundant expression of CFTR in neurons of the human brain. Techniques of double labeling and evaluation of consecutive tissue sections localized CFTR protein and mRNA signals to the cytoplasm of neurons in all regions of the brain studied, but not to glial cells. The presence of CFTR in central neurons not only provides a possible explanation for the neural symptoms observed in CF patients, but also may lead to a better understanding of the functions of CFTR in the human brain. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

Cystic Fibrosis Transmembrane Conductance Regulator Protein (CFTR) Expression in the Developing Human Brain

“…More recently, Guo and colleagues reported a much broader expression of CFTR in the adult human brain, spinal cord and sympathetic ganglia (Niu et al 2009;Guo et al 2009a;2009b). In agreement with these studies, we never found CFTR expression in radial glial cells or astrocytes but exclusively in neurons.…”

“…Lung involvement is the major cause of mortality in these patients and is dominated by recurrent infections and obstruction, finally leading to respiratory failure. Over the past 20 years, CFTR protein and its mRNA expression have progressively been reported to be present in epithelial cells of many other organs, such as the kidney (Todd-Turla et al 1996;Devuyst et al 1996), smooth muscle cells, immune cells, cardiac myocytes (Robert et al 2005) and neurons of the adult central nervous system (CNS) (Mulberg et al 1995;Johannesson et al 1997;Niu et al 2009;Guo et al 2009a;2009b). In addition, several studies have reported the expression of CFTR very early during development in immature cells of the same organs as in adulthood, suggesting a previously unsuspected role for CFTR during development (Harris et al 1991;Tizzano et al 1993).…”

Cystic fibrosis transmembrane conductance regulator protein expression in the male excretory duct system during development

“…However, functional studies have reported some CFTR chloride activity in smooth muscles and cardiomyocytes [22,23]. So far, CFTR expression has been reported in a large variety of human parenchyma including placenta [24], endothelial cells [25], smooth muscle cells [22], myocardiac cells [23], and neurons [26]. This chloride channel could contribute to multiple cellular functions in a single organ, even if the accurate functional role of CFTR in these various nonepithelial cells remains to be elucidated [27].…”

Intestinal Smooth Muscle Dysfunction Develops Postnatally in Cystic Fibrosis Mice

“…The best understood function of CFTR is as a cAMP-regulated anion channel (1). CFTR is expressed primarily in a variety of epithelia but can also be demonstrated at lower levels in numerous cell types including immune cells (2), neurons (3), neuroendocrine cells (4), and airway smooth muscle (5). The significance of CFTR expression and its loss in CF in these nonepithelial tissues is not well understood at this time.…”