Papers by Dr. T. Sathyaprabha
Supplemental Material, Consort_chart for Impact of a Course of Add-on Supervised Yoga on Cortical... more Supplemental Material, Consort_chart for Impact of a Course of Add-on Supervised Yoga on Cortical Inhibition in Major Depressive Disorder: A Randomized Controlled Trial by Praerna H. Bhargav, Preethi V. Reddy, Ramajayam Govindaraj, Kankan Gulati, Arya Ravindran, D. Gayathri, Sneha J. Karmani, Kaviraja Udupa, Ganesan Venkatasubramanian, Mariamma Philip, Monojit Debnath, Rose Dawn Bharath, T. N. Sathyaprabha, Bangalore N. Gangadhar and Kesavan Muralidharan in The Canadian Journal of Psychiatry
Details of the CSF samples taken for the study. Table S1 describes the age and gender of the subj... more Details of the CSF samples taken for the study. Table S1 describes the age and gender of the subjects, duration of disease, nature of disease progression, symptoms, onset pattern and chit-1 levels. Table S2 provides details about the age and gender matched NALS-CSF samples investigated in the present study. (DOC 41 kb)
Quantification using the inbuilt Leica software (a). The white arrowhead represents the fluoresce... more Quantification using the inbuilt Leica software (a). The white arrowhead represents the fluorescent area selected for the intensity measurement using poly-line profile for each cell, referred to as the region of interest (ROI). Twenty cells per image were considered for each of the 10 images taken per cover slip. b The report generated by the software. The mean intensity was taken for each ROI and further analyzed. (TIF 7393 KB)
Representative phase contrast (a, câ e) and confocal images of the enriched astroglial cultures (... more Representative phase contrast (a, câ e) and confocal images of the enriched astroglial cultures (b, fâ h). The reactive astrocytes display a process bearing morphology (e, h) as compared to the flat morphology adopted by the non-reactive astrocytes (c, f). The intermediate stages show a semi-reactive morphology with a transformation from flat to process bearing one (d, g). The cultures were found to be free of microglia as seen by the presence of GFAP immunoreactivity (red, j) and absence of Iba1 (green, i). In a similar manner, the cultures were found to be ChAT negative (green, l). The cultures were >99Â % pure. Scale bars are indicated. (TIF 14438 kb)
The National medical journal of India
The quantitative sudomotor axon reflex test (QSART) is an autonomic function test to evaluate the... more The quantitative sudomotor axon reflex test (QSART) is an autonomic function test to evaluate the function of postganglionic sympathetic sudomotor axons. The QSART is used for research and in clinical assessment of various neurological diseases, but few studies have assessed the influence of age, gender and reported a normative range. We assessed the influence of age and gender on QSART parameters. We recruited 61 healthy volunteers (41 men and 20 women) after obtaining written informed consent. The QSART was recorded as per standard protocol after iontophoretic stimulation (using acetylcholine) for 5 minutes. We analysed the sweat response to obtain total sweat production, rate of sweat production and latency time from the start of stimulation to sweat response. We assessed these parameters in the right medial forearm, right proximal leg, right distal leg and right proximal foot. Men had significantly higher evoked sweat volume and sweat latency period compared to women. A positive...
Journal of Neuroinflammation, 2016
Background: Non-cell autonomous toxicity is one of the potential mechanisms implicated in the eti... more Background: Non-cell autonomous toxicity is one of the potential mechanisms implicated in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). However, the exact role of glial cells in ALS pathology is yet to be fully understood. In a cellular model recapitulating the pathology of sporadic ALS, we have studied the inflammatory response of astroglia following exposure to the cerebrospinal fluid from ALS patients (ALS-CSF). Methods: Various inflammatory markers including pro-inflammatory and anti-inflammatory cytokines, COX-2, PGE-2, trophic factors, glutamate, nitric oxide (NO), and reactive oxygen species (ROS) were analyzed in the rat astroglial cultures exposed to ALS-CSF and compared with the disease control or normal controls. We used immunofluorescence, ELISA, and immunoblotting techniques to investigate the protein expression and real-time PCR to study the messenger RNA (mRNA) expression. Glutamate, NO, and ROS were estimated using appropriate biochemical assays. Further, the effect of conditioned medium from the astroglial cultures exposed to ALS-CSF on NSC-34 motor neuronal cell line was detected using the MTT assay. Statistical analysis was carried out using one-way ANOVA followed by Tukey's post hoc test, or Student's t test, as applicable. Results: Here, we report that the ALS-CSF enhanced the production and release of inflammatory cytokines IL-6 and TNF-α, as well as COX-2 and PGE-2. Concomitantly, anti-inflammatory cytokine IL-10 and the beneficial trophic factors, namely VEGF and GDNF, were down-regulated. We also found impaired regulation of glutamate, NO, and ROS in the astroglial cultures treated with ALS-CSF. The conditioned medium from the ALS-CSF exposed astroglial cultures induced degeneration in NSC-34 cells. Conclusions: Our study demonstrates that the astroglial cells contribute to the neuroinflammation-mediated neurodegeneration in the in vitro model of sporadic ALS.
Neuroscience Letters, 2010
We have earlier shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patie... more We have earlier shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients' produces selective degeneration of motor neurons, both in vitro as well as in vivo. The present study further evaluates the effect of ALS-CSF on the astrocytes in embryonic rat spinal cord cultures. We quantified the number of flat and process-bearing astrocytes in spinal cord cultures exposed to ALS-CSF and compared them against controls. In addition, GFAP and S100 expression were quantified by Western blot and measurement of immunofluorescence intensity respectively. We found higher number of process-bearing astrocytes in the cultures exposed to ALS-CSF. Both these proteins increased significantly in cultures exposed to ALS-CSF. Our results provide evidence that astroglia respond to toxic factor(s) present in ALS-CSF by undergoing morphological transformation from flat to process bearing which is further confirmed by elevated expression of GFAP and S100. The above changes could possibly alter the microenvironment hastening the motor neuron degeneration.
Neurobiology of Disease, 2011
We have earlier reported that intrathecal injection of cerebrospinal fluid (CSF) from sporadic Am... more We have earlier reported that intrathecal injection of cerebrospinal fluid (CSF) from sporadic Amyotrophic Lateral Sclerosis patients (ALS-CSF) into neonatal rats and supplementation of rat spinal cord cultures with ALS-CSF induces motor neuron degeneration via aberrant neurofilament phosphorylation and Golgi apparatus fragmentation. Intracellular aggregates immunoreactive to ubiquitin, phosphorylated neurofilaments and choline acetyl transferase (ChAT) were prominently seen in NSC-34 cells exposed to ALS-CSF. Protein aggregation could cause stress on endoplasmic reticulum (ER) and may precede Golgi fragmentation. Here we assessed the effect of ALS-CSF on the expression of GRP-78 and caspase-12 proteins, the markers of ER stress responses, in NSC-34 cells and rat spinal cords by immunochemistry and immunoblotting. Both in vitro and in vivo, increased expression of these proteins accompanied elevated active caspase-12 levels. Apoptotic nuclei and nuclear translocation of caspase-12 were noted in some cells. In vitro, the occurrence of ER stress was supported by electron microscopic observations of numerous free polyribosomes and fragmented ER cisternae. Aggregated mSOD1 protein causes ER stress in familial ALS. ER stress is also reported in the autopsy samples of sporadic ALS. Thus our observation of ER stress may be linked to the protein aggregation, viz. phosphorylated neurofilaments and ChAT, reported earlier.
Journal of the Neurological Sciences, 2007
Our earlier studies have shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (A... more Our earlier studies have shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients causes death of motor neurons, both in in-vitro as well as in-vivo. There was an aberrant phosphorylation of neurofilaments in cultured spinal cord neurons of chick and rats following exposure to CSF of ALS patients (ALS-CSF). Other features of neurodegeneration, such as swollen neuronal soma and beading of neurites were also observed. In neonatal rat pups exposed to ALS-CSF, we observed phosphorylated neurofilaments in the soma of spinal motor neurons in addition to the increased lactate dehydrogenase activity and reactive astrogliosis. The present study examines the effect of ALS-CSF on the expression of glial glutamate transporter (GLT-1) in embryonic rat spinal cord cultures as well as in spinal astrocytes of neonatal rats. Immunostaining suggested a decrease in the expression of GLT-1 by astrocytes both in culture and in-vivo following exposure to ALS-CSF. Quantification of Western blots confirmed the decreased expression of GLT-1. Our results provide evidence that toxic factor(s) present in ALS-CSF depletes GLT-1 expression. This could lead to an increased level of glutamate in the synaptic pool causing excitotoxicity to motor neurons, possibly by triggering the 'glutamate-mediated toxicity-pathway'.
Journal of Neural Transmission, 2010
Accumulating evidence supports neuroprotective role of trophic factors in amyotrophic lateral scl... more Accumulating evidence supports neuroprotective role of trophic factors in amyotrophic lateral sclerosis (ALS). Previous studies from our laboratory report that the CSF of patients with sporadic ALS (ALS-CSF) induces degenerative changes in the rat spinal motor neurons and reactive astrogliosis in the surrounding gray matter. The present study was aimed to investigate if the ALS-CSF affected the expression of trophic factors namely, brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1) in the newborn rat spinal cords. ALS-CSF was intrathecally injected into the neonatal rats and the mRNA levels of the trophic factors were determined by quantitative real-time polymerase chain reaction. Here, we report significant down regulation in the gene expression of trophic factors for BDNF, FGF2 and IGF1. BDNF mRNA levels were found to be reduced by 6.8-fold in the ALS-CSF injected group compared to control groups. The levels of IGF1 and FGF2 mRNA were also decreased by 3.91- and 2.13-fold, respectively, in the ALS group. We further found that exogenous supplementation of BDNF considerably reduced the aberrant phosphorylation of neurofilaments, complementing our earlier findings of restored expression of voltage gated sodium channel. Reduced expression of trophic factors indicates an altered microenvironment of the motor neurons and could possibly be one of the contributing factors in the degeneration process.
The Journal of Alternative and Complementary Medicine, 2012
Studies on alternative medicines for generalized anxiety disorder (GAD) are few. Manasamitra Vata... more Studies on alternative medicines for generalized anxiety disorder (GAD) are few. Manasamitra Vataka (an Ayurveda preparation) is explored for its efficacy in patients with GAD with comorbid generalized social phobia. Seventy-two (72) patients with GAD with comorbid social phobia meeting DSM IV TR criteria, and who were between the ages of 20 and 55 of either sex, participated in the study. They were randomly divided into three treatment groups: Group 1 (n=24) and Group II (n=24) received Manasamitra Vataka tablets (100 mg twice daily for 30 days). Group II, in addition to Manasamitra Vataka, underwent Shirodhara (therapy involving dripping of medicated oil [Brahmi tail] over the forehead) treatment for the first 7 days. Group III (n=24) received clonazepam 0.75 mg daily in divided dose for 30 days. The assessment of the study was done using the Hamilton Anxiety Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, Epworth Sleepiness Scale (ESS), World Health Organization Quality of Life BREF, and Clinical Global Impression scales (Improvement and Efficacy). Patients from all the groups showed significant reduction in clinical parameters evaluated. However, improvement in ESS was observed only in Group II. The treatment outcome was comparable between the three groups. This is the first study conducted on the efficacy of Manasamitra Vataka in anxiety disorders. The results suggest that Manasamitra Vataka is effective in the management GAD with comorbid generalized social phobia. Add-on effect of Shirodhara reduced the daytime sleepiness. Further studies on Manasamitra Vataka need to be carried out to judge its potential as a first-line treatment modality.
Journal of Affective Disorders, 2007
Background: Depression is associated with greater cardiac morbidity and mortality. One of the con... more Background: Depression is associated with greater cardiac morbidity and mortality. One of the contributory factors for this may be altered cardiac autonomic activity in depression. However, cardiac autonomic involvement in depression remains controversial because of methodological issues. In this study, alteration of cardiac autonomic functions was studied in drug-naive patients with major depression without co-morbidity. Heart rate variability, a sensitive measure of neurocardiac autonomic regulation was used in addition to conventional methods of measuring cardiac autonomic functions. Methods: We recruited 40 patients suffering from major depression, diagnosed based on DSM-IV-TR criteria. Their cardiac autonomic functions were measured using both conventional and heart rate variability measures. These were compared with those of age-and gender-matched healthy controls. Results: Patients with major depression showed significantly lesser Valsalva ratio, maximum/minimum ratio and greater sympathovagal balance than healthy controls indicating decreased parasympathetic and increased sympathetic activity. Conclusions: Depression is associated with alteration of cardiac autonomic tone towards decreased parasympathetic activity and an increased sympathetic activity. It is possible that a common neurobiological dysfunction contributes to both depression and cardiac autonomic changes in the illness.
Brain Research, 2009
We investigated the effect of Cerebrospinal Fluid (CSF) from sporadic Amyotrophic Lateral Scleros... more We investigated the effect of Cerebrospinal Fluid (CSF) from sporadic Amyotrophic Lateral Sclerosis patients (SALS-CSF) on motor neuron-like cells to delineate the pathomechanism of SALS. Exposure of NSC-34 cells to SALS-CSF caused lower viability, reduction in differentiation and enhanced lactate dehydrogenase activity. Additionally, reduced choline acetyl transferase expression alongside intracellular aggregation of phosphorylated neurofilaments was prominently seen. The aggregates were immunopositive for ubiquitin. These findings are comparable to the pathological changes seen in the postmortem tissue of ALS patients. Unlimited supply of NSC-34 cells and their vulnerability to SALS-CSF render them to be a good bioassay system to identify new therapeutic agents conferring protection to motor neurons.
Brain Research, 2009
Cerebro Spinal Fluid (CSF) from patients with ALS has been documented to have a toxic effect on m... more Cerebro Spinal Fluid (CSF) from patients with ALS has been documented to have a toxic effect on motor neurons both in vivo and in vitro. Here we show that the CSF from Amyotrophic Lateral Sclerosis (ALS) patients (ALS-CSF) has the potential to perturb ion channel expression, specifically the Na v 1.6, and K v 1.6 channels in newborn rat spinal motor neurons both in vivo and in vitro. ALS-CSF and CSF from nonALS patients (nonALS-CSF) were intrathecally injected into 3-day-old rat pups at the rate of 1 μl/2.5 min using a microinjector. In addition, embryonic rat spinal cord cultures were also exposed to 10% ALS or nonALS-CSF on the 9th day in vitro (9DIV) in serum free DMEM medium. After 48 h of CSF exposure, the cultures and the spinal cord sections were processed for immunostaining of the above mentioned ion channels. We observed a decrease in the expression of Na v 1.6 and K v 1.6 channels in motor neurons in ALS-CSF treated group, and the presence of trophic factors like Brain Derived Neurotrophic Factor (BDNF) and Ciliary Neurotrophic Factor CNTF partially reversed the effects produced by ALS-CSF. Altered expression of these voltagegated channels may interfere with the electrical activity of motor neurons, and thereby lead to the degeneration of neurons.
Autonomic Neuroscience, 2015
Annals of Indian Academy of Neurology
Background: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associ... more Background: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. Aims: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. Methods: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. Results: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. Conclusion: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.
The Journal of Alternative and Complementary Medicine, 2012
Background: Studies on alternative medicines for generalized anxiety disorder (GAD) are few. Mana... more Background: Studies on alternative medicines for generalized anxiety disorder (GAD) are few. Manasamitra Vataka (an Ayurveda preparation) is explored for its efficacy in patients with GAD with comorbid generalized social phobia. Materials and methods: Seventy-two (72) patients with GAD with comorbid social phobia meeting DSM IV TR criteria, and who were between the ages of 20 and 55 of either sex, participated in the study. They were randomly divided into three treatment groups: Group 1 (n = 24) and Group II (n = 24) received Manasamitra Vataka tablets (100 mg twice daily for 30 days). Group II, in addition to Manasamitra Vataka, underwent Shirodhara (therapy involving dripping of medicated oil [Brahmi tail] over the forehead) treatment for the first 7 days. Group III (n = 24) received clonazepam 0.75 mg daily in divided dose for 30 days. The assessment of the study was done using the Hamilton Anxiety Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, Epworth Sleepiness Scale (ESS), World Health Organization Quality of Life BREF, and Clinical Global Impression scales (Improvement and Efficacy). Results: Patients from all the groups showed significant reduction in clinical parameters evaluated. However, improvement in ESS was observed only in Group II. The treatment outcome was comparable between the three groups. Conclusions: This is the first study conducted on the efficacy of Manasamitra Vataka in anxiety disorders. The results suggest that Manasamitra Vataka is effective in the management GAD with comorbid generalized social phobia. Add-on effect of Shirodhara reduced the daytime sleepiness. Further studies on Manasamitra Vataka need to be carried out to judge its potential as a first-line treatment modality. Departments of 1 Neurophysiology and 2 Psychiatry, and
Research-Based Perspectives on the Psychophysiology of Yoga
Increased interest in exploring the physiological benefits of yoga in last few decades resulted i... more Increased interest in exploring the physiological benefits of yoga in last few decades resulted in plethora of scientific studies involving different physiological measures in healthy volunteers and patients with various disorders. Of these measures, autonomic functions assessment remained prime role because of wider regulation of autonomic nervous system functions over all visceral systems of the body. Through its two limbs (sympathetic and parasympathetic) autonomic nervous system regulates involuntary visceral organs and systems of the body, which is critical in maintaining the homeostasis of all the physiological functions. This homeostasis is altered in various disease conditions most of which resulted because of the increased stress, a product of modern day lifestyle. Yoga is perfect antidote for the stress, effectively tackling the dreaded effects of stress on physiological systems mainly acting through modulating sympathovagal balance to maintain the homeostasis and restorin...
The Canadian Journal of Psychiatry
Journal of chemical neuroanatomy, Jan 16, 2018
Craniopharyngiomas (CPs) are rare, epithelial tumors of the central nervous system (CNS) that cou... more Craniopharyngiomas (CPs) are rare, epithelial tumors of the central nervous system (CNS) that could lead to manifestation of multiple post-operative symptoms, ranging from hormonal imbalance to obesity, diabetes, visual, neurological and neurocognitive impairments. CP is more frequent in children, and has been reported in middle aged adults as well. In fact, arterial laceration and/or brain stroke which may occur following the removal of some CPs is mainly due to calcification of that CPs along with strong attachments to the blood vessels. The dense oily fluid content of CPs is reported to cause brain tissue damage, demyelination and axonal loss in the hypothalamus; however, its exact effect on different cell types of CNS is still unexplored. In this study, we have collected CP cyst fluid (CCF) from mostly young patients during surgical removal and exposed it 9-10 days in vitro to the primary cultures derived from rat brain hypothalamus for 48 hours. A gradual decline in cell viabil...
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Papers by Dr. T. Sathyaprabha