Search

ABSTRACT Indiscriminate use of pyrethroids has raised serious health related concerns, especially about their effects on children. The present study was designed to assess the developmental neurotoxicity of two pyrethroids; bifenthrin (BIF) and β-cyfluthrin (CYF) administered at 1/15 of LD50 in rats. Pregnant females were exposed to the test compounds orally throughout gestation and lactation periods. Neonates were weighed and sexed at birth and were observed for any gross abnormality. Growth, viability and weaning indices were calculated during the lactation period. Exposure to both the compounds did not alter the physical developmental parameters viz. eye opening, pinna detachment, and fur appearance. CYF significantly impaired growth and survivability of pups. Behavioral endpoints assessed in neonates (surface righting, pivoting, and negative geotaxis reflex) as well as adults (motor activity and motor coordination) exhibited marked effect of CYF treatment. Administration of BIF to pregnant dams impaired pivoting in neonates. Decreased locomotion in the open-field and impaired rota-rod performance were also witnessed in BIF-exposed animals. Enhanced oxidative stress was seen in corpus striatum, cerebellum, and hippocampus regions of the brain; reduced catalase, superoxide dismutase, and glutathione peroxidase activities were measured in BIF and CYF treated weanlings. Acetylcholinesterase activity was also found to be lowered following administration of both compounds at PND 21. The present results suggest that exposure to pyrethroids during critical periods of growth can induce long term effects on the behavior of animals. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1761-1770, 2016. [ABSTRACT FROM AUTHOR]

Previous studies have implicated the role of Purkinje cells in motor learning and the underlying mechanisms have also been identified in great detail during the last decades. Here we report that cyclin-dependent kinase 5 (Cdk5)/p35 in Purkinje cell also contributes to synaptic plasticity. We previously showed that p35−/− (p35 KO) mice exhibited a subtle abnormality in brain structure and impaired spatial learning and memory. Further behavioral analysis showed that p35 KO mice had a motor coordination defect, suggesting that p35, one of the activators of Cdk5, together with Cdk5 may play an important role in cerebellar motor learning. Therefore, we created Purkinje cell-specific conditional Cdk5/p35 knockout (L7-p35 cKO) mice, analyzed the cerebellar histology and Purkinje cell morphology of these mice, evaluated their performance with balance beam and rota-rod test, and performed electrophysiological recordings to assess long-term synaptic plasticity. Our analyses showed that Purkinje cell-specific deletion of Cdk5/p35 resulted in no changes in Purkinje cell morphology but severely impaired motor coordination. Furthermore, disrupted cerebellar long-term synaptic plasticity was observed at the parallel fiber-Purkinje cell synapse in L7-p35 cKO mice. These results indicate that Cdk5/p35 is required for motor learning and involved in long-term synaptic plasticity. [ABSTRACT FROM AUTHOR]

ABSTRACT Epidemiology studies have clearly documented that the central nervous system is highly susceptible to methylmercury toxicity, and exposure to this neurotoxicant in humans primarily results from consumption of contaminated fish. While the effects of methylmercury exposure have been studied in great detail, comparatively little is known about the effects of moderate to low dose methylmercury toxicity in the aging central nervous system. We examined the toxic effects of a moderate dose of methylmercury on the aging mouse cerebellum. Male and female C57BL/6 mice at 16-20 months of age were exposed to methylmercury by feeding a total dose of 5.0 mg kg−1 body weight and assessed using four behavioral tests. Methylmercury-treated aged mice performed significantly worse in open field, footprint analysis and the vertical pole test compared with age-matched control mice. Isolated cerebellar granule cells from methylmercury-treated aged mice exhibited higher levels of reactive oxygen species and reduced mitochondrial membrane potentials, but no differences in basal intracellular calcium ion levels compared with age-matched control mice. When aged mice were exposed to a moderate dose of methylmercury, they exhibited a similar degree of impairment when compared with young adult mice exposed to the same moderate dose of methylmercury, as reported in earlier studies from this laboratory. Thus, at least in mice, exposure of the aged brain to moderate concentrations methylmercury does not pose greater risk compared with the young adult brain exposed to similar concentrations of methylmercury. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]