Dr Rachna Mehta - Academia.edu (original) (raw)

Papers by Dr Rachna Mehta

Brain Sciences

Immune function and sleep are two normal physiological processes to protect the living organism f... more Immune function and sleep are two normal physiological processes to protect the living organism from falling sick. There is hardly any disease in which they remain unaffected, though the quantum of effect may differ. Therefore, we propose the existence of a strong correlation between sleep (quality or quantity) and immune response. This may be supported by the fact that sleep loss modulates many of the immunological molecules, which includes interferons; however, not much is known about their mechanism of action. Sleep is divided into rapid eye movement sleep (REMS) and non-REMS. For practical reasons, experimental studies have been conducted mostly by inducing loss of REMS. It has been shown that withdrawal of noradrenaline (NA) is a necessity for generation of REMS. Moreover, NA level increases in the brain upon REMS loss and the elevated NA is responsible for many of the sleep loss-associated symptoms. In this review, we describe how sleep (and its disturbance/loss) modulates the...

Rapid Eye Movement Sleep (REM) maintains brain excitability by modulating the brain Na-K ATPase a... more Rapid Eye Movement Sleep (REM) maintains brain excitability by modulating the brain Na-K ATPase activity. Earlier, It was reported that REMS deprivation (REMSD) associated elevated NA increases the expression of Na-K ATPase subunit as well as its enzyme activity and that is likely to be the cause of REMSD associated increased brain excitability. The Na-K ATPase is a transmembrane protein present on the cell membrane surface as well as in many organelle membranes. To be responsible for increased excitability, the α1 subunit of the Na-K ATPase must be expressed on the outer surface of the neuronal membrane, which has been confirmed in this study. We used cell impermeable Enz-link-sulfo-NHS-SS biotin that exclusively labels external surface proteins. In this study, we have shown using the Neuro2a cell line that NA (50 µM) increased Na-K ATPase α1 protein abundance on the cell surface by acting on α1- as well as β-ARs (AR). It was also observed that Chelerythrine chloride (CC) or KT570,...

Journal of Family Medicine and Primary Care

Journal of Pharmacology and Pharmacotherapeutics, 2020

Objective: To investigate the neuroprotective effects of curcumin in albino mice focusing on memo... more Objective: To investigate the neuroprotective effects of curcumin in albino mice focusing on memory and behavior. Materials and Methods: Four groups of 7 mice each, different concentrations of curcumin were administered for 3 weeks in 3 groups and the remaining group was kept as control. The effect of curcumin on behavior and memory was studied using various tests. The expression of core circadian rhythm genes and micro RNAs were also studied. Results: Our results revealed that curcumin improves the mice's behavior by regulating oxidative stress, hippocampal neurogenesis, and modulation of core circadian genes and their associated micro-RNA. Conclusion: This study shows that curcumin has a potential neuroprotective effect.

Models, Molecules and Mechanisms in Biogerontology, 2019

Rapid eye movement sleep (REMS) constitutes a distinct and unique stage within sleep, which is es... more Rapid eye movement sleep (REMS) constitutes a distinct and unique stage within sleep, which is essential for the maintenance of normal physiological processes. It is maximum in the babies, reduces with increased age, and is expressed least in the old age. REMS loss is associated with various pathophysiological disorders; expressions of several of the symptoms are common with those associated with ageing. As many of those common symptoms are induced by elevated levels of noradrenaline in the brain, we propose that the ageing-associated symptoms could be due to REMS loss and consequent increase in noradrenaline in the brain.

Clinical Epidemiology and Global Health, 2021

Although there are specific laboratory tests available for the diagnosis of Covid-19 and dengue, ... more Although there are specific laboratory tests available for the diagnosis of Covid-19 and dengue, during the present pandemic era of prioritized focus on Covid-19 assessment, there are possibilities that persons with dengue may remain undiagnosed. The present study explores the role of biochemical markers in the differential diagnosis of Covid-19 and dengue. Methods: A total of 212 participants with Acute Febrile Illness were tested for Covid-19 and dengue at the secondary care hospital, Civil Hospital Narwana, Haryana, India. The Covid-19 and dengue diagnosis were performed using standard tests followed by hematological profiling which included neutrophil lymphocyte ratio (NLR), platelet count, Vitamin D3 assessment, SGOT, SGPT, and SPO2 concentration levels. Results: Out of 212 participants, 118 were diagnosed with Covid-19 positive only, 18 dengue positive only, 5 coinfected with Covid-19 and dengue, and 71 persons with Acute Febrile Illness (control group). ANOVA revealed that mean SPO2 was significantly lower in Covid-19 and dengue than control, while SGPT and SGOT levels of Covid-19 and dengue patients were significantly higher than the control group. The mean NLR was significantly higher in Covid-19 and dengue than control and Vitamin D3 levels were significantly reduced for Covid-19 patients. Besides, thrombocytopenia was observed only in dengue patients. Conclusion: The results advocate the potential use of combinations of these makers in differential diagnosis of these two fatal viral conditions and can help by enabling the adaptation of the therapeutic conduct to the needs of individual patients.

International Archives of Otorhinolaryngology, 2020

Introduction Individual variability in the language outcomes of children with cochlear implantati... more Introduction Individual variability in the language outcomes of children with cochlear implantation (CI) is a major concern. In CI rehabilitation, there is lack of a protocol regarding uniform post-CI language assessment interval duration, which can ensure better understanding of the trajectory of language growth as well as optimize language outcomes by providing feedback in fine tuning the language intervention program. Objective To evaluate the receptive and expressive language in Hindi speaking children with up to 2 years of CI experience using revised receptive-expressive emergent language test-3ed. (REELT-3) at 6 months intervals and to compare it with that of children with normal hearing (NH). Methods The present study included 192 children divided in 2 groups, 96 children with CI (15.8 ± 6.7 months), and 96 age-matched children with NH (22.3 ± 7.9 months). A cross-sectional, prospective study design was used to measure the language ability score (LAS) at an interval of 6 mont...

Toxicology, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Purpose: Early fitting of cochlear implant (CI) enables longer access of the critical period for ... more Purpose: Early fitting of cochlear implant (CI) enables longer access of the critical period for language stimulation. In CI research, language assessment interval duration (LAID) which is a time gap between two language assessment phases, has been widely documented from the age of 2 months to 5 years and beyond. Thus, the objective of this review was to explore the

EPMA Journal, 2020

Historically and traditionally, it is known that sleep helps in maintaining healthy living. Its d... more Historically and traditionally, it is known that sleep helps in maintaining healthy living. Its duration varies not only among individuals but also in the same individual depending on circumstances, suggesting it is a dynamic and personalized physiological process. It has been divided into rapid eye movement sleep (REMS) and non-REMS (NREMS). The former is unique that adult humans spend the least time in this stage, when although one is physically asleep, the brain behaves as if awake, the dream state. As NREMS is a prerequisite for appearance of REMS, the latter can be considered a predictive readout of sleep quality and health. It plays a protective role against oxidative, stressful, and psychopathological insults. Several modern lifestyle activities compromise quality and quantity of sleep (including REMS) affecting fundamental physiological and psychopathosomatic processes in a personalized manner. REMS loss-induced elevated brain noradrenaline (NA) causes many associated symptoms, which are ameliorated by preventing NA action. Therefore, we propose that awareness about personalized sleep hygiene (including REMS) and maintaining optimum brain NA level should be of paramount significance for leading physical and mental well-being as well as healthy living. As sleep is a dynamic, multifactorial, homeostatically regulated process, for healthy living, we recommend addressing and treating sleep dysfunctions in a personalized manner by the health professionals, caregivers, family, and other supporting members in the society. We also recommend that maintaining sleep profile, optimum level of NA, and/or prevention of elevation of NA or its action in the brain must be seriously considered for ameliorating lifestyle and REMS disturbance-associated dysfunctions.

International Journal of Pediatric Otorhinolaryngology, 2020

INTRODUCTION Selection of an effective tool for assessment of language learning outcomes in post ... more INTRODUCTION Selection of an effective tool for assessment of language learning outcomes in post cochlear implantation is always an important but challenging task. Receptive expressive emergent language test-3rd Eds. (REELT-3) is one of the comprehensive language assessment tools used in India. In case of administration of REELT-3, which is standardized in English speaking typically developing western population, to another language speaking population with post-cochlear implant condition, the test outcome may get compromised owing to linguistics and population variability. The objective of the study is to test and validate REELT-3 in Hindi speaking children with cochlear implantation. METHODS Ninety six typically developing children (22.3 ± 6.9 months, 48 boys and 48 girls) and 96 children with cochlear implantation (25.8 ± 9.2 months, 57 boys and 39 girls) participated in this study. As per the eligibility criteria of REELT-3, infants and toddlers with cochlear implant of age below 36 months participated in this study. Criterion, content and construct validity were tested using correlation based statistical analysis. RESULTS High content validity was established by obtaining very low correlation coefficient r = 0.16 across two distinct population of typically developing children and children with cochlear implantation. Similarly, correlation coefficient of r = 0.84 revealed high criterion validity across REELT-3 in English and Hindi speaking conditions. Finally, correlation coefficient of r = 0.87was obtained between language raw score and chronological age to establish construct validity. Chronbach alpha coefficient (Chronbach α = 0.85) and interclass correlation coefficient 0.87was observed for REELT-3 which suggests good internal consistency and test-retest reliability, respectively. Receiver Operating Characteristics curve analysis of the REELT-3 suggested that area under curve 0.95 (95% CI = 0.89-0.99, p < 0.001) is excellent. The cut-off Language Ability Score (LAS) was determined as 74.5 with the sensitivity of 87.9% and specificity of 84.1% infer high sensitivity and specificity. CONCLUSIONS These results validate that REELT-3 can be used in assessment of language outcome in Hindi speaking children with post-cochlear implantation. Clinical assessment of receptive and expressive language will be beneficial in effective evaluation as well as in therapeutic planning.

Cellular and Molecular Neurobiology, 2019

Parkinson's disease (PD) is an age-related, threatening neurodegenerative disorder with no reliab... more Parkinson's disease (PD) is an age-related, threatening neurodegenerative disorder with no reliable treatment till date. Identification of specific and reliable biomarker is a major challenge for disease diagnosis and designing effective therapeutic strategy against it. PD pathology at molecular level involves abnormal expression and function of several proteins, including alpha-synuclein. These proteins affect the normal functioning of neurons through various post-translational modifications and interaction with other cellular components. The role of protein anomalies during PD pathogenesis can be better understood by the application of proteomics approach. A number of proteomic studies conducted on brain tissue, blood, and cerebrospinal fluid of PD patients have identified a wide array of protein alterations underlying disease pathogenesis. However, these studies are limited by the types of brain regions or biofluids utilized in the research. For a complete understanding of PD mechanism and discovery of reliable protein biomarkers, it is essential to analyze the proteome of different PD-associated brain regions and easily accessible biofluids such as saliva and urine. The present review summarizes the major advances in the field of PD research in humans utilizing proteomic techniques. Moreover, potential samples for proteomic analysis and limitations associated with the analyses of different types of samples have also been discussed.

Nature and science of sleep, 2018

Rapid eye movement sleep (REMS) is a unique phenomenon essential for maintaining normal physiolog... more Rapid eye movement sleep (REMS) is a unique phenomenon essential for maintaining normal physiological processes and is expressed at least in species higher in the evolution. The basic scaffold of the neuronal network responsible for REMS regulation is present in the brainstem, which may be directly or indirectly influenced by most other physiological processes. It is regulated by the neurons in the brainstem. Various manipulations including chemical, elec-trophysiological, lesion, stimulation, behavioral, ontogenic and deprivation studies have been designed to understand REMS genesis, maintenance, physiology and functional significance. Although each of these methods has its significance and limitations, deprivation studies have contributed significantly to the overall understanding of REMS. In this review, we discuss the advantages and limitations of various methods used for REMS deprivation (REMSD) to understand neural regulation and physiological significance of REMS. Among the d...

World Journal of Neurology, 2017

Neuroscience Letters, 2015

Rapid eye movement sleep (REMS) serves house-keeping function of the brain and its loss affects s... more Rapid eye movement sleep (REMS) serves house-keeping function of the brain and its loss affects several pathophysiological processes. Relative levels of neurotransmitters including orexin A (Orx-A) in various parts of the brain in health and diseases are among the key factors for modulation of behaviors, including REMS. The level of neurotransmitter in an area in the brain directly depends on number of projecting neurons and their firing rates. The locus coeruleus (LC), the site of REM-OFF neurons, receives densest, while the pedunculo-pontine area (PPT), the site of REM-ON neurons receives lesser projections from the Orx-ergic neurons. Further, the Orx-ergic neurons are active during waking and silent during REMS and NREMS. Therefore, the level of Orx-A in discrete regions of the brain is likely to be different during normal and altered states, which in turn is likely to be responsible for altered behaviors in health and diseases, including in relation to REMS. Therefore, in the present study, we estimated Orx-A level in LC, cortex, posterior hypothalamus (PH), hippocampus, and PPT after 96h REMSD, in post-deprivation recovered rats and in control rats. This is the first report of estimation of Orx-A in different brain regions after prolonged REMSD. It was observed that after REMSD the Orx-A level increased significantly in LC, cortex and PH which returned to normal level after recovery; however, the level did not change in the hippocampus and PPT. The Orx-A induced modulation of REMS could be secondary to increased waking.

Neurochemistry International, 2017

Rapid eye movement sleep (REMS) plays important role in maintenance of normal brain functions. Ne... more Rapid eye movement sleep (REMS) plays important role in maintenance of normal brain functions. Neurons containing various neurotransmitters in different brain regions interact to regulate this complex phenomenon in health and diseases. The number of neuronal projections, their firing rates and neurotransmitter levels vary in different brain regions under various conditions leading to normal or altered patho-physio-behavioral states. In this study using high performance liquid chromatography (HPLC) we quantified noradrenaline (NA) and gamma-amino butyric acid (GABA) levels in locus coeruleus (LC), dorsal raphe (DR), pedunculo-pontine tegmentum (PPT), frontal lobe (FL), cortex and hippocampus (Hippo) in control and after 96 h REMS deprivation (REMSD) rats. Normal free moving control (FMC) rats were taken as standard cage controls. To rule out non-specific effects large platform control (LPC) and post-REMSD recovery (REC) were carried out. The levels of NA and GABA in discrete brain regions upon REMSD were statistically compared with all the controls. Upon REMSD, although NA levels significantly increased and the GABA levels decreased in the LC, PPT and cortex, in Hippo their levels showed opposite responses. Only NA levels increased in FL, while only GABA levels were decreased in the DR after REMSD. Most of the altered neurotransmitter levels returned to normal levels in REC rats. The findings help understanding the neurochemical basis of REMSD and its associated effects.

Cells, 2020

It is a well-known fact that following a proper routine light/dark or diurnal rhythm controls alm... more It is a well-known fact that following a proper routine light/dark or diurnal rhythm controls almost all biological processes. With the introduction of modern lighting and artificial illumination systems, continuous exposure to light at night may lead to the disruption of diurnal rhythm. However, the effect of light during the night on brain anatomy, physiology, and human body functions is less explored and poorly understood. In this study, we have evaluated the effect of exposure to dim light (5 lux) at night (dLAN) on Swiss Albino mice over a duration of three consecutive weeks. Results have revealed that exposure to dLAN led to an impairment of cognitive and non-cognitive behaviour, oxidative stress–mediated elevation of lipid peroxidation, and reduction of superoxide dismutase and catalase activity. It also led to the downregulation of hippocampal proteins (BDNF, Synapsin II and DCX) at both protein and mRNA level. Additionally, there was downregulation of CREB and SIRT1 mRNAs a...

Current Neuropharmacology, 2016

Sleep is an essential physiological process, which has been divided into rapid eye movement sleep... more Sleep is an essential physiological process, which has been divided into rapid eye movement sleep (REMS) and non-REMS (NREMS) in higher animals. REMS is a unique phenomenon that unlike other sleep-waking states is not under voluntary control. Directly or indirectly it influences or gets influenced by most of the physiological processes controlled by the brain. It has been proposed that REMS serves housekeeping function of the brain. Extensive research has shown that during REMS at least noradrenaline (NA)-ergic neurons must cease activity and upon REMS loss, there are increased levels of NA in the brain, which then induces many of the REMS loss associated acute and chronic effects. The NA level is controlled by many bio-molecules that are regulated at the molecular and transcriptional levels. Similarly, NA can also directly or indirectly modulate the synthesis and levels of many molecules, which in turn may affect physiological processes. The burgeoning field of behavioral neuroepigenetics has gained importance in recent years and explains the regulatory mechanisms underlying several behavioral phenomena. As REMS and its loss associated changes in NA modulate several pathophysiological processes, in this review we have attempted to explain on one hand how the epigenetic mechanisms regulating the gene expression of factors like tyrosine hydroxylase (TH), monoamine oxidase (MAO), noradrenaline transporter (NAT) control NA levels and on the other hand, how NA per se can affect other molecules in neural circuitry at the epigenetic level resulting in behavioral changes in health and diseases. An understanding of these events will expose the molecular basis of REMS and its loss-associated pathophysiological changes; which are presented as a testable hypothesis for confirmation.

eNeuro

Normally, rapid eye movement sleep (REMS) does not appear during waking or non-REMS. Isolated, in... more Normally, rapid eye movement sleep (REMS) does not appear during waking or non-REMS. Isolated, independent studies showed that elevated noradrenaline (NA) levels inhibit REMS and induce REMS loss-associated cyto-Significance Statement Reciprocal interactions among rapid eye movement (REM)-ON and REM-OFF neurons in pedunculo-pontine tegmentum (PPT) and locus coeruleus (LC), respectively, have been proposed to regulate REM sleep (REMS). Findings from isolated independent studies led to the proposition that noradrenaline (NA) from the latter inhibits the former to prevent REMS, and that its withdrawal initiates REMS by disinhibiting the former, while excess NA causes REMS loss-associated symptoms. However, evidence from direct in vivo studies confirming this idea was lacking. Using RNAi technology in vivo, we show that NA from LC neurons prevents REMS by inhibiting PPT neurons and that those LC neurons are the source of NA for inducing REMS loss-associated symptoms. These confirmatory findings in animal models are the first proof-of-principle that holds the potential for exploitation in ameliorating REMS loss-associated symptoms in patients. New Research November/December 2016, 3(6) e0108-16.2016 1-19 molecular, cytomorphological, psychosomatic changes and associated symptoms. However, the source of NA and its target in the brain for REMS regulation and function in health and diseases remained to be confirmed in vivo. Using tyrosine hydroxylase (TH)-siRNA and virus-coated TH-shRNA in normal freely moving rats, we downregulated NA synthesis in locus coeruleus (LC) REM-OFF neurons in vivo. These TH-downregulated rats showed increased REMS, which was prevented by infusing NA into the pedunculo-pontine tegmentum (PPT), the site of REM-ON neurons, normal REMS returned after recovery. Moreover, unlike normal or control-siRNA-or shRNA-injected rats, upon REMS deprivation (REMSD) TH-downregulated rat brains did not show elevated Na-K ATPase (molecular changes) expression and activity. To the best of our knowledge, these are the first in vivo findings in an animal model confirming that NA from the LC REM-OFF neurons (1) acts on the PPT REM-ON neurons to prevent appearance of REMS, and (2) are responsible for inducing REMSD-associated molecular changes and symptoms. These observations clearly show neuro-physio-chemical mechanism of why normally REMS does not appear during waking. Also, that LC neurons are the primary source of NA, which in turn causes some, if not many, REMSD-associated symptoms and behavioral changes. The findings are proof-of-principle for the first time and hold potential to be exploited for confirmation toward treating REMS disorder and amelioration of REMS loss-associated symptoms in patients.