Relationship between consanguinity and depression in a south Indian population.

A Pilot study was Carried out to study the association of consanguinity marriage with depression. It was observed that the consanguinity of marriage was associated with depression. The odds ratio was 5.66 (CI: 2.42-13.54). The age and sex had an association with depression. The age and sex adjusted odds ratio of consanguinity marriage was 7.66 (CI: 3.93-19.45) indicating that it is independently associated with depression.

Frontiers in the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive dementia and brain deposits of the amyloid ß protein (Aß) as senile plaques and the microtubule-associated protein, Tau, as neurofibrillary tangles (NFT). The current treatment of AD is limited to drugs that attempt to correct deficits in the cholinergic pathway or glutamate toxicity. These drugs show some improvement over a short period of time but the disease ultimately requires treatment to prevent and stop the neurodegeneration that affects multiple pathways. The currently favored hypothesis is that Aß aggregates to toxic forms that induce neurodegeneration. Drugs that reduce Aß successfully treat transgenic mouse models of AD, but the most promising anti-Aß vaccination approach did not successfully treat AD in a clinical trial. These studies suggest that AD pathogenesis is a complex phenomenon and requires a more broad-based approach to identify mechanisms of neurodegeneration. Multiple hypotheses have been proposed and the field is ready for a new generation of ideas to develop early diagnostic approaches and develop successful treatment plans.

Studies on genomic DNA topology and stability in brain regions of Parkinson's disease.

DNA damage has been postulated as a mechanism of neuronal death in Parkinson's disease (PD). In the present study, genomic DNA was isolated from eight brain regions (frontal, temporal, and occipital cortex, hippocampus, caudate/putamen, thalamus, cerebellum, and midbrain) from five neuropathologically confirmed cases of Parkinson's disease and six control brains and analyzed for the presence of single and double strand breaks, melting temperature, EtBr intercalation, DNAse digestion pattern, and DNA conformations. The results showed that DNA from midbrain in PD accumulated significantly higher number of strand breaks than age-matched controls. Caudate nucleus/putamen, thalamus, and hippocampus also showed more DNA fragmentation compared to control brains. Circular dichroism studies showed that DNA conformation was altered with imprecise base stacking in midbrain, caudate nucleus/putamen, thalamus, and hippocampus in PD. However, DNA from frontal, temporal, and occipital cortex, and cerebellum was not affected significantly in PD group as compared to controls. This study provides a comprehensive database on stability, damage, and conformations of DNA in different regions in brains of PD patients.

Aluminium in Alzheimer's disease: are we still at a crossroad?

Aluminium, an environmentally abundant non-redox trivalent cation has long been implicated in the pathogenesis of Alzheimer's disease (AD). However, the definite mechanism of aluminium toxicity in AD is not known. Evidence suggests that trace metal homeostasis plays a crucial role in the normal functioning of the brain, and any disturbance in it can exacerbate events associated with AD. The present paper reviews the scientific literature linking aluminium with AD. The focus is on aluminium levels in brain, region-specific and subcellular distribution, its relation to neurofibrillary tangles, amyloid beta, and other metals. A detailed mechanism of the role of aluminium in oxidative stress and cell death is highlighted. The importance of complex speciation chemistry of aluminium in relation to biology has been emphasized. The debatable role of aluminium in AD and the cross-talk between aluminium and genetic susceptibility are also discussed. Finally, it is concluded based on extensive literature that the neurotoxic effects of aluminium are beyond any doubt, and aluminium as a factor in AD cannot be discarded. However, whether aluminium is a sole factor in AD and whether it is a factor in all AD cases still needs to be understood.

Challenges and complexities of alpha-synuclein toxicity: new postulates in unfolding the mystery associated with Parkinson's disease.

The discovery of two missense mutations in alpha-synuclein gene and the identification of the alpha-synuclein as the major component of Lewy bodies and Lewy neurites have imparted a new direction in understanding Parkinson's disease. Now that alpha-synuclein has been implicated in several neurodegenerative disorders makes it increasingly clear that aggregation of alpha-synuclein is a hallmark feature in neurodegeneration. Although little has been learned about its normal function, alpha-synuclein appears to be associated with membrane phospholipids and may therefore participate in a number of cell signaling pathways. Here, we review the localization, structure, and function of alpha-synuclein and provide a new hypothesis on, (a) the disruption in the membrane binding ability of synuclein which may be the major culprit leading to the alpha-synuclein aggregation and (b) the complexity associated with nuclear localization of alpha-synuclein and its possible binding property to DNA. Further, we postulated the three possible mechanisms of synuclein induced neuronal degeneration in Parkinson's disease.

Quantification of trace elements in normal human brain by inductively coupled plasma atomic emission spectrometry.

Eight normal human brain autopsy samples were analyzed for Na, K, P, Ca, Mg, Si, Cr, Cu, Ni, Zn, Fe, Al, Cd, Pb and As in 12 regions of brain (frontal cerebrum, temporal cerebrum, parietal cerebrum, somatosensory cortex, occipital cerebrum, cerebellum, mid-brain, pons, hypothalamus, thalamus, hippocampus and medulla oblongata) using inductively coupled plasma atomic emission spectrometry (ICPAES). The distribution of these 15 elements varied significantly from region to region of the brain. Potassium was most abundant in nearly all regions of the brain, followed by sodium and phosphorus (mg/g). The concentration of Al was found to be comparatively high and varied in different areas of the brain (58-196 microg/g). Moderate levels of Pb, Cd and As were observed in different regions. Ratios of Al to Fe were found to be high in temporal cerebrum (8.07) and hippocampus (9.05) and these two regions are significantly involved in Alzheimer's disease. The concentration of Na in mole percentage showed an inverse correlation with that of K, Ca, Mg, Fe and Cr. Direct correlation was observed in the concentration of all analyzed elements, which indicated for the first time the direct dependency of concentration of trace elements in one brain region to other regions. The mole ratios between different elements in different brain regions and total amounts of the elements in an average weight of 1.4 kg human brain were also computed. The present study provides new and in-depth data which may be used as base line data for normal human brains.