Chandipura Virus-New Insights

This virus was discovered by NIV, Pune in 1965 in two adults suffering from febrile illness in Napur area of Maharashtra. It was isolated from sandflies around Aurangabad in 1970 (Dhanda V et al, IJMR,1970). Isolation have also been reported from Madhya Pradesh, Nigeria. In 2003, there was an encephalitis epidemic in Andhrapradhesh, Maharashtra just at monsoon onset and 183/329 children died in Andhrapradesh only. Patients complained abdominal pain had vomiting, acute enphalitis/encephalopathy features leading to death with in 48 hours of hospitalization. Neurological sequel in recovered cases is a rare occurrence which is a sigh of relief.

NIV which was established in 1952 under auspices of ICMR and Rockefellar Foundation has played a pivotal role in understanding this disease.

This virus belongs to Rabies virus family (Rhabdoviridae) and as shown in picture (taken from NIV, CHP virus poster) has bullet shape and lower stained canal!

Tripathy et al (Scand J Infect Dis. 2005;37(8):590-3)reported significant change in INF-Gamma, IL-2 compared to controls, whereas IL-6 and TNF-Alpha were higher in patients with >2 days of illness compared to controls.

Here authors show that there is blood brain barrier breach early in infection as measured by evans blue dye exclusion test. Young mice are susceptible to infection IV, IP and intracerebral mode where as adults are susceptible only via intracerebral route. Raise in proinflammatory cytokines like TNF-alpha, INF-gamma, IL2, IL6 with 24 hours of infection can aid leak in BBB. Authors also saw that IgM antibody for virus appears as early as 72 hours post infection which seems to decrease blood viral load but cant decrease CNS load. CD4+, CD8+ and CD19+ cells were also less in infected mice and antigen specific suppression of T cell proliferation was witnessed at 72 hours. Authors also report that passive immunization was able to prevent infection before viral infection and not at 24 hours post infection.

This paper is a significant step in understanding the etiopathogenesis of this viral infection.

Immune response during acute Chandipura viral infection in experimentally infected susceptible mice
Virol J. 2008; 5: 121. Published online 2008 October 20(click here to read the paper)

Anukumar Balakrishnan(1) and Akhilash Chandra Mishra(2)
1 Chandipura virus group
2 Director, National Institute of Virology, 20-A, Dr. Ambedkar Road, Post Box-11, Pune-411001, Maharashtra, India

Illegal Settlements in Brain

Neeraj Jain et al report large scale reorganization of somatosensory cortex in macaque monkey brain post partial or complete dorsal hemiresection of the cervical spinal cord. This work however was not done in India but at Vanderbilt university, USA where he did his postdoctoral work. He continues to map brain using similar methods at NBRC(His NBRC webpage).

Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22–23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.

The Journal of Neuroscience, October 22, 2008, 28(43):11042-11060

This is not exactly Neuroscience but has implications in it

Nanoclusters of GPI-anchored proteins are formed by cortical actin-driven activity.
Cell. 2008 Dec 12;135(6):1085-9
Goswami D, Gowrishankar K, Bilgrami S, Ghosh S, Raghupathy R, Chadda R, Vishwakarma R, Rao M, Mayor S.
National Centre for Biological Sciences (TIFR), Bellary Road, Bangalore 560065, India.

Several cell-surface lipid-tethered proteins exhibit a concentration-independent, cholesterol-sensitive organization of nanoscale clusters and monomers. To understand the mechanism of formation of these clusters, we investigate the spatial distribution and steady-state dynamics of fluorescently tagged GPI-anchored protein nanoclusters using high-spatial and temporal resolution FRET microscopy. These studies reveal a nonrandom spatial distribution of nanoclusters, concentrated in optically resolvable domains. Monitoring the dynamics of recovery of fluorescence intensity and anisotropy, we find that nanoclusters are immobile, and the dynamics of interconversion between nanoclusters and monomers, over a range of temperatures, is spatially heterogeneous and non-Arrhenius, with a sharp crossover coinciding with a reduction in the activity of cortical actin. Cholesterol depletion perturbs cortical actin and the spatial scale and interconversion dynamics of nanoclusters. Direct perturbations of cortical actin activity also affect the construction, dynamics, and spatial organization of nanoclusters. These results suggest a unique mechanism of complexation of cell-surface molecules regulated by cortical actin activity

Aluminium and Alzheimers'!!!

Sandeep Tripathi et al from CDRI, Lucknow are publishing their research in Brain Research Journal. The topic is controversial "Aluminium and Alzheimers disease" related. Issue was upheld when aluminium was detected in neurofibrillary tangles (DP Perl et al, Science, 1980)and a study suggested a geographical correlation between aluminium and alzheimers in the journal Lancet (C N Martyn et al, Lancet 1989). And so the story goes on. Aluminium is used in water cleaning, utensils etc and hence a potential for a toxic metal to induce neurological changes exists.

According to authors, aluminium ingestion (100mg/Kg) caused reduction in body weight, brain weight more evident in aged male wistar rats. Treated aged rats had less relearning index in Y-maze test compared to untreated or even young treated ones!

Aged as well as young treated rats had less protein, more lipid, more conjugated dienes, more lipid peroxides and hydroperoxides, more lipofuscin compared to untreated age-matched controls. They also had significant less levels of catalase, superoxide dismutase, glutathion reduced as well as peroxidase along with increased levels of Iron, decreased Selenium and Copper.

n=12 in each group (Young control and treated=~6 months, Aged control and treated=~24 months). Its not not clear to me atlest whether they gave 100mg/kg AlCl3 mixed with 1% gum acacia for 90days to treated group.

Overall, this paper suggests that aluminium has age related effects of inducing oxidative stress and causes accumulation of lipofuscin in frontal cortex of wistar rats.

I just want to comment that aluminium concentration used does seem to be too high.
Reiko Matsuda et al ( Journal of the Food Hygienic Society of Japan(2001)) suggest daily dietary intake to be 1.8 to 8.4 mg..we dont know whats the scenario in India).

Ciba Foundation Symposium 169 - Aluminium in Biology and Medicine book excert is given below. Author is J L Greger

Aluminium in the food supply comes from natural sources including water, food additives, and contamination by aluminium utensils and containers. Most unprocessed foods, except for certain herbs and tea leaves, contain low (<5 µg Al/g) levels of aluminium. Thus most adults consume 1-10 mg aluminium daily from natural sources. Cooking in aluminium containers often results in statistically significant, but not practically important, increases in the aluminium content of foods. Intake of aluminium from food additives varies greatly (0 to 95 mg Al daily) among residents in North America, with the median intake for adults being about 24 mg daily. Generally, the intake of aluminium from foods is less than 1% of that consumed by individuals using aluminium-containing pharmaceuticals. Currently the real scientific question is not the amount of aluminium in foods but the availability of the aluminium in foods and the sensitivity of some population groups to aluminium. Several dietary factors, including citrate, may affect the absorption of aluminium. Aluminium contamination of soy-based formulae when fed to premature infants with impaired kidney function and aluminium contamination of components of parenteral solutions (i.e. albumin, calcium and phosphorus salts) are of concern.

This "metal ions" causing problems theory is gonna stay untill we pinpoint the exact cause of Alzheimers disease and produce a perfect model of it (apart from current so called Alzheimer models..are majorly just models of amyloidosis kind of disorders!!)

Long way to go in this but this atleast lets us know of ill effects of Aluminium.

Influence of age on aluminum induced lipid peroxidation and neurolipofuscin in frontal cortex of rat brain: A behavioral, biochemical and ultrastructural study

Brain Research, Article in Press,
doi:10.1016/j.brainres.2008.11.060

Sandeep Tripathi,Abbas Ali Mahdi, Akbar Nawab, Ramesh Chander,Mahdi Hasan,Mohammad Shakil Siddiqui,Farzana Mahdi,Kalyan Mitra and Virendra Kumar Bajpai

Department of Biochemistry, King George’s Medical University
Department of Anatomy, King George’s Medical University
Department of Biochemistry, Era’s Lucknow Medical College
Electron Microscopy Division, Central Drug Research Institute, Lucknow, India 226003

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Another study in the Brain Research Journal by Kumar V et al (PGIMER, Chandigarh) reports impairment in mitochondrial energy metabolism in wistar rats receving 10mg/kg body weight aluminium for 12 weeks. They also found decreased levels of SOD and Glutathion as well as increased ROS.

Intake is still high compared to human estimates (10mg/60Kg=0.16mg/Kg)

Impairment of mitochondrial energy metabolism in different regions of rat brain following chronic exposure to aluminium.

Kumar V, Bal A, Gill KD.
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.

Brain Res. 2008 Sep 26;1232:94-103. Epub 2008 Jul 16

Epilepsy Prevalence: Kolkata

This epidemiological study puts out interesting findings. According to the study (door to door stratified random sampling). Prevalence of active epilepsy (< or = 19 years of age) is in the range of 0.58-0.83 % which is well below average epilepsy prevalence 1% (see Satishchandra et al). However febrile seizures prevalence was found to be 0.9-1.2%. 9.5% of febrile seizures developed epilepsy later on which is higher than western data. One third of cerebral palsy patients had epilepsy.

This paper re-emphasizes our need to concentrate on epilepsy, diagnosis and treatment strategies.

Indian J Pediatr. 2008 Dec 4. [Epub ahead of print]
Neurological disorders in children and adolescents - An epidemiological study
Banerjee TK, Hazra A, Biswas A, Ray J, Roy T, Raut DK, Chaudhuri A, Das SK.
National Neurosciences Centre, Kolkata, India

Fishmap!

This is mind blowing!! IGIB has come up with Zebrafish Genomics databse.freely available. I guess India is aiming deep in ebrafish science. This tiny little fish is a new tool in developmental biology and sure is here to stay

http://fishmap.igib.res.in/

All the best!!

Invivo antioxidant status: A putative target of antidepressant action

This is an interesting paper from Department of Life Sciences, Aligarh Muslim University. Bilici et al (2001)reported changes Glutathione peroxidase (GSHPx)and Melondialdehyde (p<0.05) in plasma and significant change in (p<0.05)GSH-Px and SOD in erythrocytes-no Melondialdehyde!-of major depression (with or without melancholia) compared to healthy controls. sub chronic reatment of these patients with SSRIs (Sertraline, Fluoxetin, Citalopram and Fluvoxamine) significantly decreased (p<0.01) GSHpx and melondialdehyde in plasma and SOD and Melondialdehyde in erythrocytes. Micheal et al in 2007 reported increased SOD levels in PFC of patient with depressive disorder when compared to controls (vascular problem matched) but the difference was significant in hippocampus.
This paper induces depression in animal models by immobility and measures it by forced swimming and sucrose preference tests both are corrected by antidepressant treatment (Imipramine, Fluoxetine and Venlafexine-most commonly used antidepressant!!)
Their stress model has less SOD, CAT, GST, GR, GSH and incresed MDA and Carbomoyl content compared to controls. Only MDA data is in line with human subjects plama levels so I doubt that this model can indeed give out all features (including molecular) of depression. Neverthless MDA can itself activate PLCA2, oxidize PUFAs and inhibit serotonin receptors. Also SSRI treatment decreased MDA and Carbomoyl levels and restored SOD levels to that comparable to control animals. Which suggests that SSRIs might be fighting oxidative stress and lipid peroxidation might be important feature of such behavioral abnormalities.

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Progress in Neuro-Psychopharmacology and Biological Psychiatry
In Vivo Antioxidant Status: A Putative Target Of Antidepressant Action
In Press, Accepted Manuscript, Available online 30 November 2008
Ayesha Zafir, Anjum Ara, Naheed Banu
Department of Biochemistry, and 2Department of Zoology, Faculty of Life Sciences, A.M.University, Aligarh, U.P., India

Abstract:Oxidative stress is a critical route of damage in various psychological stress-induced disorders,
such as depression. Antidepressants are widely prescribed to treat these conditions; however, fewanimal studies have investigated the effect of these drugs on endogenous antioxidant status in thebrain. The present study employed a 21-day chronic regimen of random exposure to restraintstress to induce oxidative stress in brain, and behavioural aberrations, in rodents. The forcedswimming (FST) and sucrose preference tests were used to identify depression-like phenotypes,and reversal in these indices indicated the effectiveness of treatment with fluoxetine (FLU; 20mg/kg/day, p.o.; selective serotonin reuptake inhibitor), imipramine (IMI; 10 mg/kg/day, p.o.;
tricyclic antidepressant) and venlafaxine (VEN; 10 mg/kg/day, p.o.; dual serotonin/norepinephrine reuptake inhibitor) following restraint stress. The antioxidant statuswas investigated in the brain of these animals. The results evidenced a significant recovery in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST),glutathione reductase (GR) and glutathione (GSH) levels by antidepressant treatments following a restraint stress-induced decline of these parameters. The severely accumulated lipid peroxidation product malondialdehyde (MDA) and protein carbonyl contents in stressed animals
were significantly normalized by antidepressant treatments. The altered oxidative status is implicated in various aspects of cellular function affecting the brain. Thus, it is possible that augmentation of in vivo antioxidant defenses could serve as a convergence point for multiple classes of antidepressants as an important mechanism underlying the neuroprotective pharmacological effects of these drugs observed clinically in the treatment of various stress disorders. Consequently, pharmacological modulation of stress-induced oxidative damage as a possible stress-management approach should be an important avenue of further research

Neuroanatomical correlates of neurological soft signs in antipsychotic-naive schizophrenia

Ganesan Venkatasubramanian, Peruvumba N. Jayakumar, Bangalore. N. Gangadhar and Matcheri S. Keshavan

(all except Keshavan are at NIMHANS, Bangalore. Dr. M Keshavan who is one of the main pillars of schizophrenia research is at Detroit, USA)

This is a first of its kind paper to have analysed Soft Neurological Signs in drug-naive schizophrenics to a greater detail (barring Keshavans' earlier work on cerebellum and Bottmer et al). However many years of research has indeed told us about changes in prefrontal cortex volumes, superior temporal gyrus volume etc to be different in schizos, this study establishes a correlation of them to clinical features especially motor sequece signs, hence ascertaining neuroarchitectal basis of observed motor behaviour and also implicating neurocircuitry involvment at large. This paper pushes schizophrenia as to a neurodevelopmental disorder and not a neurodegenerative disorder. Look into Keshavan's papers for more details.

Abstract

Recent imaging studies suggest that the so-called “soft” neurological signs in schizophrenia might have neuroanatomical validity. We examined gray matter volume correlates of neurological soft signs (NSS) in antipsychotic-naive schizophrenia patients using an automated image analysis technique. NSS were assessed using a modified neurological evaluation scale with good inter-rater reliability. Magnetic resonance images of 30 schizophrenia patients and 27 age-, sex-, education- and handedness-matched healthy controls were processed using optimized voxel-based morphometry (VBM). Logistic regression analysis showed that only the Motor Sequencing Signs (MSS) sub-score was a significant predictor of subject's status among the NSS sub-scores. Optimized VBM analysis showed that the MSS sub-score had a significant negative correlation with total and regional gray matter volumes (prefrontal, posterior cingulate, temporal cortices, putamen, and cerebellum) in schizophrenia patients but not in controls. Prefrontal and temporal cortices, putamen and cerebellum had significant volume deficits in patients. Cortical and cerebellar correlates of the sub-score MSS support the concept of “cognitive dysmetria” in schizophrenia.

Psychiatry Research: Neuroimaging
Article in Press, Corrected Proof
doi:10.1016/j.pscychresns.2007.12.021

Prospective comparison of course of disability in antipsychotic-treated and untreated schizophrenia patients.

Acta Psychiatr Scand. 2008 Nov 24; [Epub ahead of print]

Thirthalli J, Venkatesh BK, Kishorekumar KV, Arunachala U, Venkatasubramanian G, Subbakrishna DK, Gangadhar BN.

Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India.

Prospective comparison of course of disability in antipsychotic-treated and untreated schizophrenia patients.

Objective: To compare the course of disability in schizophrenia patients receiving antipsychotics and those remaining untreated in a rural community. Method: Of 215 schizophrenia patients identified in a rural south Indian community, 58% were not receiving antipsychotics. Trained raters assessed the disability in 190 of these at baseline and after 1 year. The course of disability in those who remained untreated was compared with that in those who received antipsychotics.

Results: Mean disability scores remained virtually unchanged in those who remained untreated, but showed a significant decline (indicating decrement in disability) in those who continued to receive antipsychotics and in those in whom antipsychotic treatment was initiated (P < 0.001; group x occasion effect). The proportion of patients classified as 'disabled' declined significantly in the treated group (P < 0.01), but remained the same in the untreated group.

Conclusion: Disability in untreated schizophrenia patients remains unchanged over time. Treatment with antipsychotics in the community results in a considerable reduction in disability.

Welcome Home!

This blog has only one purpose. To report and analyze neuroscience research done or being done in India.

What is being done in India regarding neuroscience? Yes we have NIMHANS, NCBS, NBRC and Jiwaji University and few other important institutes. What is being done there? In fact what has India offered to neuroscience till now?

To answer this question, I typed "India" as affiliation and neuroscience as subject in SCOPUS (ofcourse it did not pick up many papers which have relation to neuroscience especially molecular biology ones, and including Rajan and Uppi bhalla's Science paper!), neverthless it returned almost 7200+ articles. Number of neuroscience related articles being published in neuroscience related journals is increasing exponentially. Looks like there was a sudden boom at around mid 70s and around late 90's. I dont know the reason! But neuroscience is here to stay. So lets get to work!