Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders

Stressor exposure during early life has the potential to increase an individual’s susceptibility to a number of neuropsychiatric conditions such as mood and anxiety disorders and schizophrenia in adulthood. This occurs in part due to the dysfunctional stress axis that persists following early adversity impairing stress responsivity across life. The mechanisms underlying the prolonged nature of this vulnerability remain to be established. Alterations in the epigenetic signature of genes involved in stress responsivity may represent one of the neurobiological mechanisms. The overall aim of this review is to provide current evidence demonstrating changes in the epigenetic signature of candidate gene(s) in response to early environmental adversity. More specifically, this review analyses the epigenetic signatures of postnatal adversity such as childhood abuse or maltreatment and later-life psychopathology in human and animal models of early life stress. The results of this review shows that focus to date has been on genes involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and its correlation to subsequent neurobiology, for example, the role of glucocorticoid receptor gene. However, epigenetic changes in other candidate genes such as brain-derived neurotrophic factor (BDNF) and serotonin transporter are also implicated in early life stress (ELS) and susceptibility to adult psychiatric disorders. DNA methylation is the predominantly studied epigenetic mark followed by histone modifications specifically acetylation and methylation. Further, these epigenetic changes are cell/tissue-specific in regulating expression of genes, providing potential biomarkers for understanding the trajectory of early stress-induced susceptibility to adult psychiatric disorders

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Not AvailableIdentification of full length genes along with upstream regulatory elements is important to understand its expression. Here, we report preparation of high titre genomic library and identification of a genomic clone containing Pi-kh gene with its complete upstream and downstream sequences from the rice blast resistant line Tetep. Structural analysis of protein revealed that Pi-kh has a central nucleotide binding site domain, leucine-rich repeats domain and a unique zinc-finger domain. Comparative analysis of Pi-kh protein sequence showed 64% and 45% similarity with the protein sequences of rice blast resistance genes Pi-b and Pi-ta, respectivelyNot Availabl

Preservation of native conformation during aluminium-induced aggregation of tau protein

ALUMINIUM exposure has been shown to result in aggregation of microtubule-associated protein tau in vitro. In the light of recent observations that the native random structure of tau protein is maintained in its monomeric and dimeric states as well as in the paired helical filaments characteristic of Alzheimer's disease, it is likely that factors playing a causative role in neurofibrillary pathology would not drastically alter the native conformation of tau protein. We have studied the interaction of tau protein with aluminium using circular dichroism (CD) and 27(Al) NMR spectroscopy. The CD studies revealed a five-fold increase in the observed ellipticity of the tau-aluminium assembly. The increase in elipticity was not associated with a change in the general conformation of the protein and was most likely due to an aggregation of the tau protein induced by aluminium. Al-27 NMR spectroscopy confirmed the binding of aluminium to tau protein. Hyperphosphorylation of tau in Alzheimer's disease is known to be associated with defective microtubule assembly in this condition. Abnormally phosphorylated tau exists in a polymerized form in the paired helical filaments (PHF) which constitute the neurofibrillary tangles found in Alzheimer's disease. While it is hypothesized that its altered biophysical characteristics render abnormally phosphorylated tau resistant to proteolysis, causing the formation of stable deposits,the sequence of events resulting in the polymerization of tau are little understood, as are the additional factors or modifications required for tills process. Based on the results of our spectroscopic studies, a model for the sequence of events occurring in neurofibrillary pathology is proposed

Betaine reverses toxic effects of aluminium: Implications in Alzheimer's disease (AD) and AD-like pathology

Impairment in T-maze erformance of aduIt rats P, caused by altminiurn $(A1^{3+})$ and the reversal of it by betaine, a methyl donor, was studied. Besides, conformational change in the secondary structure of $\beta$ amloid peptide $(A\beta)$ brought about by the addition of $(A1^{3+})$ in vitro, was also studied using CD-spectroscopy. The organisrnal study proved that betaine is effective in restoring the memory loss caused by $(A1^{3+})$ possibly through augmentation of choline leveIs, as betaine is involved in the synthesis of choline. The CD-spectra recorded indicate loss of $\alpha$ -helical content of the peptide $(A\beta)$ caused by the addition of $(A1^{3+})$ , which was reversed to some extent by the addition of betaine. Betaine may thus preventlstop the progression of plaque formation seen during the initial stages of Alzheimer's disease (AD), and AD-like pathology as the loss of secondary structure of $A\beta$ is suspected to be an early event in the aetiopathology of ADIAD-like perturbations caused by Al toxicity. Betaine, a natural product occurring in beetroot (Beta vulgaris), and a by product in the process of manufacturing beet sugar may thus prove efficacious in the treatment of diseases involving dysfunctions of cholinergic system leading to memory loss

Electroconvulsive Therapy Alters Dopamine Signaling in the Striatum of Non-human Primates

Electroconvulsive therapy (ECT) is one of the most effective therapies for depression and has beneficial motor effects in parkinsonian patients. However, little is known about the mechanisms of therapeutic action of ECT for either condition. The aim of this work was to explore the impact of ECT on dopaminergic function in the striatum of non-human primates. Rhesus monkeys underwent a course of six ECT treatments under a human clinical protocol. Longitudinal effects on the dopaminergic nigrostriatal system were studied over 6 weeks using the in vivo capabilities of positron emission tomography (PET). PET scans were performed prior to the onset of ECT treatments and at 24–48 h, 8–10 days, and 6 weeks after the final ECT treatment. Early increases in dopamine transporter and vesicular monoamine transporter 2 binding returned to baseline levels by 6 weeks post-ECT. Transient increases in D1 receptor binding were also observed, whereas the binding potential to D2 receptors was unaltered. The increase in dopaminergic neurotransmission suggested by our results may account in part for the therapeutic effect of ECT in mood disorders and Parkinson's disease