ABSTRACT

In earlier studies, we discovered multi-lamellar, electron-dense membrane stacks in the developing UN rat Purkinje neurons (Sharma et al. 1986; Sharma et al. 1987; Sharma et al. 1993). Subsequently, these peculiar structures were identified in the hippocampal CA-3 and dentate gyrus neurons of intra-uterine KA and DOM-exposed mice; and were named as “CBs” (Sharma et al. 1993; Dakshinamuti et al. 1993; Sharma 2013). Hippocampal microinjection of 5-HT1A receptor agonist, 8-hydroxy-DPAT in the dentate gyrus inhibited DOM-induced seizures in male adult rats (Sharma and Dakshinamurti 1993). Later, we reported that stress-induced free radical overproduction may cause CB formation in the hippocampal neurons due to degeneration of mitochondria in PD, AD, drug addiction, and depression (Sharma et al. 2014). Nutritional rehabilitation, Zn2+, and MTs inhibit CB formation in the rat brain (Sharma et al. 2013). Recently, we reported that MTs inhibit CB formation and provide ubiquinone (CoQ10)-mediated neuroprotection by serving as potent free radical scavengers (Sharma and Ebadi 2014). MTs are low molecular weight, cysteine-rich, Zn2+-binding proteins and are induced in nutritional stress and in response to NPs toxicity (Sharma et al. 2013). MTs regulate Zn2+-mediated transcriptional activation of genes and microRNA-mediated post-transcription involved in DNA cell cycle, growth, proliferation, differentiation, and development may serve as early and sensitive biomarkers of NDDs, CVDs, and cancer (Sharma et al. 2013; Sharma and Ebadi 2013).