Rapid Eye Movement Sleep Deprivation Induces Neuronal Apoptosis by Noradrenaline Acting on Alpha1 Adrenoceptor and by Triggering Mitochondrial Intrinsic Pathway

Many neurodegenerative disorders are associated with rapid eye movement sleep (REMS)-loss, however the mechanism was unknown. As REMS-loss elevates noradrenaline (NA) level in the brain as well as induces neuronal apoptosis and degeneration, in this study we have delineated the intracellular molecular pathway involved in REMS deprivation (REMSD) associated NA-induced neuronal apoptosis. Rats were REMS deprived for 6 days by the classical flower-pot method, suitable controls were conducted and the effects on apoptosis markers evaluated. Further, the role of NA was studied by one, intraperitoneal (i.p.) injection of NA-ergic alpha1-adrenoceptor antagonist prazosin (PRZ) and two, by down-regulation of NA synthesis in locus coeruleus (LC) neurons by local microinjection of tyrosine hydroxylase siRNA (TH-siRNA). Immunoblot estimates showed that the expressions of pro-apoptotic proteins viz. Bcl2-associated death promoter (BAD) protein, apoptotic protease activating factor-1 (Apaf-1), cytochrome c, caspase9, caspase3 were elevated in the REMS-deprived rat brains, while caspase8 level remained unaffected; PRZ treatment did not allow elevation of these pro-apoptotic factors. Further, REMSD increased cytochrome c expression, which was prevented if the NA synthesis from the LC neurons was blocked by microinjection of TH-siRNA in vivo into the LC during REMSD in freely moving normal rats. Mitochondrial damage was re-confirmed by transmission electron microscopy (TEM), which showed distinctly swollen mitochondria with disintegrated cristae, chromosomal condensation and clumping along the nuclear membrane and all these changes were prevented in PRZ treated rats. Combining findings of this study along with earlier reports we propose that upon REMSD NA level increases in the brain as the LC NA-ergic REM-OFF neurons do not cease firing and TH is up-regulated in those neurons. This elevated NA acting on alpha1-adrenoceptors damages mitochondria causing release of cytochrome c to activate intrinsic pathway for inducing neuronal apoptosis in REMS deprived rat brain

R778L, H1069Q, and I1102T mutation study in neurologic Wilson disease

There is paucity of the studies on mutations in neurologic Wilson disease (WD) in India. We studied H1069Q, R778L, I1102T mutations in 26 patients with neurologic WD from 25 families in north India. The basis of diagnosis of neurologic WD was clinical, Kayser-Fleischer (KF) ring, and ceruloplasmin. Data collected included: family history, clinical characteristics, laboratory data, ultrasound findings, magnetic resonance imaging (MRI) findings, and severity of the disease. DNA was isolated from venous blood and subjected to H1069Q, R778L, and I1102T mutation study. The age range was 5-41 years. Family history was present in 8 patients. The H1069Q, R778L, and I1102T mutations were absent in all the patients and in 16 parents and siblings. Severity of the illness was related to the extent of MRI changes but not with age of onset and hepatic involvement. H1069Q, R778L, and I1102T mutations were absent in our patients, which may be due to genetic and ethnic heterogeneity and further studies are required

Phosphodiesterase 4 D Gene Polymorphism in Relation to Intracranial and Extracranial Atherosclerosis in Ischemic Stroke

In ischemic stroke, extracranial MR angiography (ECMRA) is more frequently abnormal in Caucasians and intracranial (ICMRA) in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D) gene polymorphism and its correlation with MRA findings in patients with ischemic stroke

Lasers in glaucoma

While lasers have been used for many years for the treatment of glaucoma, proper indications and use of the procedures need to be considered before their application. This review summarizes the important laser procedures in Glaucoma