The fungicide mancozeb increases oxygen-free radicals in the central nervous system. As an antioxidant, L-carnitine protects DNA and cell membranes from damage caused by oxygen-free radicals. The present study investigated how L-carnitine affected the acoustic startle response (ASR) in rats exposed to mancozeb. In this experimental study, male Wistar rats were gavaged orally with mancozeb (500, 1000, and 2000 mg/kg), L-carnitine (100, 200, and 400 mg/kg), or L-carnitine (200 mg/kg) + mancozeb (500 mg/kg) three times in 1 week. In the sham group, saline (0.9%, 10 mL/kg) was gavaged at a volume equivalent to that of the drugs. The control group did not receive any treatment. The results showed that locomotor activity and the percentage of prepulse inhibition in the mancozeb groups decreased compared to the sham group while these parameters increased in the L-carnitine group (200 mg/kg) compared to sham rats. In conclusion, mancozeb may increase the risk factor for cognitive diseases such as schizophrenia in people exposed to it while pretreatment with L-carnitine can attenuate the toxic effect.
Background: Phospholipase A-2-activating protein (PLAP) has essential roles in biological pathways. Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA) is a complex neurodevelopmental disease caused by defects in the PLAA gene (MIM: 603873). Herein, we aimed to detect the potential genetic factors contributing to the NDMSBA phenotype in a 2.5-year-old affected male in an Iranian consanguineous family.Methods: After meticulously performing neuroimaging and clinical examinations, due to heterogeneity of neurodevelopmental diseases, the proband was subjected to paired-end whole-exome sequencing (WES). The candidate variant was confirmed by Sanger sequencing and different in silico predictions were used to show the pathogenicity of the variant. Results: The brain magnetic resonance imaging revealed lissencephaly, polymicrogyria, severe subcortical, deep and deep white matter signal abnormalities, thinning of the corpus callosum, and severe vermis atrophy. Interestingly, we detected a novel homozygous missense variant, NM_001031689.3:c.2264A>G;p.(Asp755Gly) in the PLAA gene. To the best of our knowledge, this variant is the second one identified within the PUL domain (PLAP, Ufd3p, and Lub1p) of PLAP and also the sixth reported variant throughout the PLAA gene. In silico analyses underscored the pathogenicity of the variant. Conclusions: The present study demonstrated severe cerebral and cerebellar white matter signal abnormalities, hypertelorism, strabismus, and drooling in the proband as the novel manifestation of NDMSBA that in turn caused by a novel likely pathogenic missense variant. Further studies are required to confirm how this variant contributes to NDMSBA.
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