Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina
Authors: Sachin Tripathi
Kalyan Mitra
Sanghamitra Bandyopadhyay
Nagendra Kumar Rai
Asit Rai
Geet Kumar Nagar
Anushruti Ashok
Journal: Toxicology and Applied Pharmacology (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Brn3b; CNS-disruption; Demyelination; MBP; Metal mixture
Affiliations: Academy of Scientific and Innovative Research, India; Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), India.

Abstract:  Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2'-, 3'-cyclic-nucleotide-3'-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. 

Retracted: No

PubPeer comments:
 Figure 3 was brought to my attention by a reader. * The gel does not look like a real photo. Rather, these appear computer generated white lines on a pitch black background.  , 
 Figure 2: * This does not look like a real photo either. The bands are pitch black, all have the same shape, and the background is uniform grey.  , 
 Figure 1. * Could the authors please clarify the name of the *Zuckerberg pneumonia* ? Is this a newly discovered bacterial species? I have never heard of it and neither has Google - or Facebook.  , 
 The original of Fig 1 appears to be [ Modified Hodge Test (MHT) for Carbapenemase detection: Principle, Method and Interpretations ] , a web page from 2015.  That original version is captioned  The MHT performed on a 100 mm MHA plate. (1) K[lebsiella] pneumoniae ATCC BAA 1705, positive result (2) K. pneumoniae ATCC BAA 1706, negative result; and (3) a clinical isolate, positive result . , 
 #3 ATCC700603 is a Klebsiella pneumoniae strain. ,