sneha
@unipune.ac.in
Department of Zoology
Savitribai Phule Pune University
EDUCATION
Ph.D. Biotechnology
RESEARCH INTERESTS
Neuroscience, Epigenetics, Neuropeptides, Aging, Reward
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Shobha Bhargava, Ketaki Shetye, Swapnil Shewale, Nitin Sawant, Sneha Sagarkar, and Nishikant Subhedar
Elsevier BV
Sneha Sagarkar, Nagashree Bhat, Madhura Sapre, Biru Dudhabhate, Dadasaheb M. Kokare, Nishikant K. Subhedar, and Amul J. Sakharkar
Springer Science and Business Media LLC
Kavita N. Hadawale, Swapnil A. Shewale, Ketaki C. Shetye, Sneha Sagarkar, Amul J. Sakharkar, and Shobha Y. Bhargava
Elsevier BV
Sanjay N. Awathale, Akash M. Waghade, Harish M. Kawade, Gouri Jadhav, Amit G. Choudhary, Sneha Sagarkar, Amul J. Sakharkar, Nishikant K. Subhedar, and Dadasaheb M. Kokare
Springer Science and Business Media LLC
Coincident excitation via different sensory modalities encoding objects of positive salience is known to facilitate learning and memory. With a view to dissect the contribution of visual cues in inducing adaptive neural changes, we monitored the lever press activity of a rat conditioned to self-administer sweet food pellets in the presence/absence of light cues. Application of light cues facilitated learning and consolidation of long-term memory. The superior colliculus (SC) of rats trained on light cue showed increased neuronal activity, dendritic branching, and brain-derived neurotrophic factor (BDNF) protein and mRNA expression. Concomitantly, the hippocampus showed augmented neurogenesis as well as BDNF protein and mRNA expression. While intra-SC administration of U0126 (inhibitor of ERK 1/2 and long-term memory) impaired memory formation, lidocaine (local anaesthetic) hindered memory recall. The light cue-dependent sweet food pellet self-administration was coupled with increased efflux of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens shell (AcbSh). In conditioned rats, pharmacological inhibition of glutamatergic signalling in dentate gyrus (DG) reduced lever press activity, as well as DA and DOPAC secretion in the AcbSh. We suggest that the neuroplastic changes in the SC and hippocampus might represent memory engrams sculpted by visual cues encoding reward information.
Nagalakshmi Balasubramanian, Sneha Sagarkar, Meha Jadhav, Navneet Shahi, Richa Sirmaur, and Amul J. Sakharkar
S. Karger AG
<b><i>Introduction:</i></b> Repeated traumatic events result in long-lasting neuropsychiatric ailments, including neuroendocrine imbalances. Neuropeptide Y (NPY) in the arcuate nucleus (Arc) is an important orexigenic peptide. However, the molecular underpinnings of its dysregulation owing to traumatic brain injury remain unknown. <b><i>Methods:</i></b> Rats were subjected to repeated mild traumatic brain injury (rMTBI) using the closed head weight-drop model. Feeding behavior and the regulatory epigenetic parameters of NPY expression were measured at 48 h and 30 days post-rMTBI. Further, sodium butyrate (SB), a pan-histone deacetylase (HDAC) inhibitor, was administered to examine whether histone deacetylation is involved in NPY expression post-rMTBI. <b><i>Results:</i></b> The rMTBI attenuated food intake, which was coincident with a decrease in NPY mRNA and protein levels in the Arc post-rMTBI. Further, rMTBI also reduced the mRNA levels of the cAMP response element-binding protein (CREB) and CREB-binding protein (CBP) and altered the mRNA levels of the various isoforms of the HDACs. Concurrently, the acetylated histone 3-lysine 9 (H3-K9) levels and the binding of CBP at the NPY promoter in the Arc of the rMTBI-exposed rats were reduced. However, the treatment with SB corrected the rMTBI-induced deficits in the H3-K9 acetylation levels and CBP occupancy at the NPY promoter, restoring both NPY expression and food intake. <b><i>Conclusions:</i></b> These findings suggest that histone deacetylation at the NPY promoter persistently controls NPY function in the Arc after rMTBI. This study also demonstrates the efficacy of HDAC inhibitors in mitigating trauma-induced neuroendocrine maladaptations in the hypothalamus.
Sneha Sagarkar, Amit G. Choudhary, Nagalakshmi Balasubramanian, Sanjay N. Awathale, Amita R. Somalwar, Namrata Pawar, Dadasaheb M. Kokare, Nishikant K. Subhedar, and Amul J. Sakharkar
Elsevier BV
Nagalakshmi Balasubramanian, Sneha Sagarkar, Amit G. Choudhary, Dadasaheb M. Kokare, and Amul J. Sakharkar
Springer Science and Business Media LLC
The recurrent events of mild trauma exacerbate the vulnerability for post-traumatic stress disorder; however, the underlying molecular mechanisms are scarcely known. The repeated mild traumatic brain injury (rMTBI) perturbs redox homeostasis which is primarily managed by superoxide dismutase 2 (SOD2). The current study investigates the role of DNA methylation in SOD2 gene regulation and its involvement in rMTBI-induced persistent neuropathology inflicted by weight drop injury paradigm. The oxidative damage, neurodegenerative indicators, and SOD2 function and its regulation in the hippocampus were analyzed after 48 h and 30 days of rMTBI. The temporal and episodic increase in ROS levels (oxidative stress) heightened 8-hydroxyguanosine levels indicating oxidative damage after rMTBI that was concomitant with decline in SOD2 function. In parallel, occupancy of DNMT3b at SOD2 promoter was higher post 30 days of the first episode of rMTBI causing hypermethylation at SOD2 promoter. This epigenetic silencing of SOD2 promoter was sustained after the second episode of rMTBI causing permanent blockade in SOD2 response. The resultant oxidative stress further culminated into the increasing number of degenerating neurons. The treatment with 5-azacytidine, a pan DNMT inhibitor, normalized DNA methylation levels and revived SOD2 function after the second episode of rMTBI. The release of blockade in SOD2 expression by DNMT inhibition also normalized the post-traumatic oxidative consequences and relieved the neurodegeneration and deficits in learning and memory as measured by novel object recognition test. In conclusion, DNMT3b-mediated DNA methylation plays a critical role in SOD2 gene regulation in the hippocampus, and the perturbations therein post rMTBI are detrimental to redox homeostasis manifesting into neurological consequences.
Kavita N. Hadawale, Sneha Sagarkar, and Shobha Y. Bhargava
Elsevier BV
Nagalakshmi Balasubramanian, Abhinav Srivastava, Namrata Pawar, Sneha Sagarkar, and Amul J. Sakharkar
Elsevier BV
Dollwin Matharu, Dhiraj Dhotre, Nagalakshmi Balasubramanian, Namrata Pawar, Sneha Sagarkar, and Amul Sakharkar
Springer Science and Business Media LLC
Traumatic brain injuries (TBI) manifest into post-traumatic stress disorders such as anxiety comorbid with gut ailments. The perturbations in gut microbial communities are often linked to intestinal and neuropsychological disorders. We have previously reported anxiety and abnormalities in gut function in mild TBI (MTBI)-exposed rats. The current study demonstrates the changes in gut microbiome of MTBI-exposed animals and discusses its implications in intestinal health and behaviours. The rats were subjected to repeated MTBI (rMTBI) and microbial composition in jejunum was examined after 6 h, 48 h and 30 days of rMTBI. Significant reduction in bacterial diversity was observed in the rMTBI-exposed animals at all the time points. Principal coordinate analysis based on weighted UniFrac distances indicated substantial differences in gut microbial diversity and abundances in rMTBI-exposed animals as compared to that in healthy controls. The abundance of Proteobacteria increased dramatically with reciprocal decrease in Firmicutes after rMTBI. At the genus level, Helicobacter, Lactobacillus, Campylobacter, and Streptococcus were found to be differentially abundant in the jejunum of rMTBI-exposed rats as compared to sham controls indicating profound dysbiosis from the healthy state. Furthermore, substantial depletion in butyrate-producing bacterial communities was observed in rMTBI-exposed animals. These results suggest that the traumatic stress alters the gut microbiome with possible implications in gut health and neuropsychopathology.
Sneha Sagarkar, Nagalakshmi Balasubramanian, Shruti Mishra, Amit G. Choudhary, Dadasaheb M. Kokare, and Amul J. Sakharkar
Elsevier BV
Omprakash Singh, Dipti R. Pradhan, B. Nagalakashmi, Santosh Kumar, Saptarsi Mitra, Sneha Sagarkar, Amul J. Sakharkar, Ronald M. Lechan, and Praful S. Singru
Wiley
Thyrotropin‐releasing hormone (TRH) regulates the hypothalamic–pituitary–thyroid axis in mammals and also regulates prolactin secretion, directly or indirectly via tuberoinfundibular dopamine neurons. Although TRH is abundantly expressed in teleost brain and believed to mediate neuronal communication, empirical evidence is lacking. We analyzed pro‐TRH‐mRNA expression, mapped TRH‐immunoreactive elements in the brain and pituitary, and explored its role in regulation of hypophysiotropic dopamine (DA) neurons in the catfish, Clarias batrachus. Partial pro‐TRH transcript from C. batrachus transcriptome showed six TRH progenitors repeats. Quantitative real‐time polymerase chain reaction (qRT‐PCR) identified pro‐TRH transcript in a number of different brain regions and immunofluorescence showed TRH‐immunoreactive cells/fibers in the olfactory bulb, telencephalon, preoptic area (POA), hypothalamus, midbrain, hindbrain, and spinal cord. In the pituitary, TRH‐immunoreactive fibers were seen in the neurohypophysis, proximal pars distalis, and pars intermedia but not rostral pars distalis. In POA, distinct TRH‐immunoreactive cells/fibers were seen in nucleus preopticus periventricularis anterior (NPPa) that demonstrated a significant increase in TRH‐immunoreactivity when collected during preparatory and prespawning phases, reaching a peak in the spawning phase. Although tyrosine hydroxylase (TH)‐immunoreactive neurons in NPPa are hypophysiotropic, none of the TRH‐immunoreactive neurons in NPPa accumulated neuronal tracer DiI following implants into the pituitary. However, 87 ± 1.6% NPPa TH‐immunoreactive neurons were surrounded by TRH‐immunoreactive axons that were seen in close proximity to the somata. Superfused POA slices treated with TRH (0.5–2 μM) significantly reduced TH concentration in tissue homogenates and the percent TH‐immunoreactive area in the NPPa. We suggest that TRH in the brain of C. batrachus regulates a range of physiological functions but in particular, serves as a potential regulator of hypophysiotropic DA neurons and reproduction.
Kavita N. Hadawale, Nitin S. Sawant, Sneha Sagarkar, Amul J. Sakharkar, and Shobha Y. Bhargava
Elsevier BV
Chandrashekhar D. Borkar, Sneha Sagarkar, Amul J. Sakharkar, Nishikant K. Subhedar, and Dadasaheb M. Kokare
Wiley
Although chronic nicotine administration does not affect memory, its withdrawal causes massive cognitive deficits. The underlying mechanisms, however, have not been understood. We test the role of cocaine‐ and amphetamine‐regulated transcript peptide (CART), a neuropeptide known for its procognitive properties, in this process. The mice on chronic nicotine treatment/withdrawal were subjected to novel object recognition task. The capability of the animal to discriminate between the novel and familiar objects was tested and represented as discrimination index (DI); reduction in the index suggested amnesia. Nicotine for 49 days had no effect on DI, but 8‐hour withdrawal caused a significant reduction, followed by full recovery at 24‐hour withdrawal timepoint. Bilateral CART infusion in dorsal hippocampus rescued deficits in DI at 8‐hours, whereas CART‐antibody infusion into the dorsal hippocampus attenuated the recovery at 24‐hours. Commensurate changes were observed in the CART as well as CART mRNA profiles in the hippocampus. CART mRNA expression and the peptide immunoreactivity did not change significantly following chronic nicotine treatment. However, there was a significant reduction at 8‐hour withdrawal, followed by a drastic increase in CART immunoreactivity as well as CART mRNA at 24‐hour withdrawal, compared with 8‐hour withdrawal. Distinct α7‐nicotinic receptor immunoreactivity was detected on the hippocampal CART neurons, suggesting cholinergic inputs. An increase in the synaptophysin immunoreactive elements around CART cells in the dentate gyrus, cornu ammonis 3 and subiculum at 24‐hour post‐withdrawal timepoint suggested neuronal plasticity. CART circuit dynamics in the hippocampus seems to modulate short‐term memory associated with nicotine withdrawal.
Amita R. Somalwar, Amit G. Choudhary, Pravesh R. Sharma, Nagalakshmi B., Sneha Sagarkar, Amul J. Sakharkar, Nishikant K. Subhedar, and Dadasaheb M. Kokare
Elsevier BV
Amit G. Choudhary, Amita R. Somalwar, Sneha Sagarkar, Abhishek Rale, Amul Sakharkar, Nishikant K. Subhedar, and Dadasaheb M. Kokare
Springer Science and Business Media LLC
Paraventricular thalamic nucleus (PVT) serves as a transit node processing food and drug-associated reward information, but its afferents and efferents have not been fully defined. We test the hypothesis that the CART neurons in the lateral hypothalamus (LH) project to the PVT neurons, which in turn communicate via the glutamatergic fibers with the nucleus accumbens shell (AcbSh), the canonical site for reward. Rats conditioned to self-stimulate via an electrode in the right LH–medial forebrain bundle were used. Intra-PVT administration of CART (55–102) dose-dependently (10–50 ng/rat) lowered intracranial self-stimulation (ICSS) threshold and increased lever press activity, suggesting reward-promoting action of the peptide. However, treatment with CART antibody (intra-PVT) or MK-801 (NMDA antagonist, intra-AcbSh) produced opposite effects. A combination of sub-effective dose of MK-801 (0.01 µg/rat, intra-AcbSh) and effective dose of CART (25 ng/rat, intra-PVT) attenuated CART’s rewarding action. Further, we screened the LH–PVT–AcbSh circuit for neuroadaptive changes induced by conditioning experience. A more than twofold increase was noticed in the CART mRNA expression in the LH on the side ipsilateral to the implanted electrode for ICSS. In addition, the PVT of conditioned rats showed a distinct increase in the (a) c-Fos expressing cells and CART fiber terminals, and (b) CART and vesicular glutamate transporter 2 immunostained elements. Concomitantly, the AcbSh showed a striking increase in expression of NMDA receptor subunit NR1. We suggest that CART in LH–PVT and glutamate in PVT–AcbSh circuit might support food-seeking behavior under natural conditions and also store reward memory.
Nagalakshmi B., Sneha Sagarkar, and Amul J. Sakharkar
Elsevier
Sneha Sagarkar, Tanmayi Bhamburkar, Gajanan Shelkar, Amit Choudhary, Dadasaheb M. Kokare, and Amul J. Sakharkar
Elsevier BV
S. Sagarkar, S. Mahajan, A. G. Choudhary, C. D. Borkar, D. M. Kokare, and A. J. Sakharkar
Wiley
Stress‐induced chronic neuropsychiatric conditions such as anxiety are often co‐morbid with gastrointestinal malfunctions. While we find enduring anxiety‐like symptoms following minimal traumatic brain injury (MTBI) in rats, gastrointestinal consequences of MTBI remain elusive.
S. Sagarkar and A. Sakharkar
Elsevier
Atya Kapley, Sneha Sagarkar, Deepa Gandhi, SSaravana Devi, and Amul Sakharkar
Medknow
Objective: Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of nuclear- and mitochondrial-encoded genes involved in oxidative phosphorylation (OXPHOS) in human liver (HepG2) and rat muscle (L6) cell lines due to short-term atrazine exposure. Materials and Methods: We have determined the EC50 values of atrazine for cytotoxicity and mitochondrial toxicity (mitotoxicity) in terms of adenosine triphosphate (ATP) content in HepG2 and L6 cells. Further, the mRNA expression of nuclear- and mitochondrial-encoded genes was analyzed using quantitative real-time polymerase chain reaction. Results: The EC50 value of atrazine for mitotoxicity in HepG2 and L6 cells was found to be about 0.162 and 0.089 mM, respectively. Mitochondrial toxicity was indicated by reduction in ATP content following atrazine exposure. Atrazine exposure resulted in down-regulation of many OXPHOS subunits expression and affected biogenesis factors’ expression. Most prominently, superoxide dismutase (SOD) and sirtuin 3 (SIRT3) expressions were up-regulated in HepG2 cells, whereas SIRT3 expression was alleviated in L6 cells, without significant changes in SOD levels. Mitochondrial transcription factor A (TFAM) and SIRT1 expression were significantly down-regulated in both cell lines. Conclusion: Results suggest that TFAM and SIRT1 could be involved in atrazine-induced mitochondrial dysfunction, and further studies can be taken up to understand the mechanism of mitochondrial toxicity. Further study can also be taken up to explore the possibility of target genes as biomarkers of pesticide toxicity.
Atya Kapley, Himgouri Tanksale, Sneha Sagarkar, A. R. Prasad, Rathod Aravind Kumar, Nandita Sharma, Asifa Qureshi, and Hemant J. Purohit
Springer Science and Business Media LLC
Alcaligenes sp. HPC 1271 demonstrated antibacterial activity against multidrug resistant bacteria, Enterobacter sp., resistant to sulfamethoxazole, ampicillin, azithromycin, and tetracycline, as well as against Serratia sp. GMX1, resistant to the same antibiotics with the addition of netilmicin. The cell-free culture supernatant was analyzed for possible antibacterials by HPLC, and the active fraction was further identified by LC-MS. Results suggest the production of tunicamycin, a nucleoside antibiotic. The draft genome of this bacterial isolate was analyzed, and the 4.2 Mb sequence data revealed six secondary metabolite-producing clusters, identified using antiSMASH platform as ectoine, butyrolactone, phosphonate, terpene, polyketides, and nonribosomal peptide synthase (NRPS). Additionally, the draft genome demonstrated homology to the tunicamycin-producing gene cluster and also defined 30 ORFs linked to protein secretion that could also play a role in the antibacterial activity observed. Gene expression analysis demonstrated that both NRPS and dTDP-glucose 4,6-dehydratase gene clusters are functional and could be involved in antibacterial biosynthesis.
Sneha Sagarkar, Pooja Bhardwaj, Veronika Storck, Marion Devers-Lamrani, Fabrice Martin-Laurent, and Atya Kapley
Springer Science and Business Media LLC
The Arthrobacter sp. strain AK-YN10 is an s-triazine pesticide degrading bacterium isolated from a sugarcane field in Central India with history of repeated atrazine use. AK-YN10 was shown to degrade 99 % of atrazine in 30 h from media supplemented with 1000 mg L−1 of the herbicide. Draft genome sequencing revealed similarity to pAO1, TC1, and TC2 catabolic plasmids of the Arthrobacter taxon. Plasmid profiling analyses revealed the presence of four catabolic plasmids. The trzN, atzB, and atzC atrazine-degrading genes were located on a plasmid of approximately 113 kb.The flagellar operon found in the AK-YN10 draft genome suggests motility, an interesting trait for a bioremediation agent, and was homologous to that of Arthrobacter chlorophenolicus. The multiple s-triazines degradation property of this isolate makes it a good candidate for bioremediation of soils contaminated by s-triazine pesticides.
Aura O. Nousiainen, Katarina Björklöf, Sneha Sagarkar, Jeppe Lund Nielsen, Atya Kapley, and Kirsten S. Jørgensen
Springer Science and Business Media LLC
Strategies for bioremediation of atrazine, a pesticide commonly polluting groundwater in low concentrations, were studied in two boreal nonagricultural soils. Atrazine was not mineralized in soil without bioremediation treatments. In biostimulation treatment with molasses, up to 52 % of atrazine was mineralized at 10 °C, even though the degradation gene copy numbers did not increase. Incubations with radioactively labeled atrazine followed by microautoradiographic analysis revealed that bioremediation strategies increased the relative proportion of active degraders from 0.3 up to 1.9 % of the total bacterial count. These results indicate that atrazine degradation might not solely be facilitated by atzA/trzN–atzB genes. In combined biostimulation treatment using citrate or molasses and augmentation with Pseudomonas citronellolis ADP or Arthrobacter aurescens strain TC1, up to 76 % of atrazine was mineralized at 30 °C, and the atrazine degradation gene numbers increased up to 107 copies g−1 soil. Clone libraries from passive samplers in groundwater monitoring wells revealed the presence of phylogenetic groups formerly shown to include atrazine degraders, and the presence of atrazine degradation genes atzA and atzB. These results show that the mineralization of low concentrations of atrazine in the groundwater zone at low temperatures is possible by bioremediation treatments.
RECENT SCHOLAR PUBLICATIONS
MOST CITED SCHOLAR PUBLICATIONS
Publications
1) Sagarkar S., Choudhary AG., Balasubramanian N., Awathale SN., Somalwar AR., Pawar N., Kokare DM., Subhedar NK., Sakharkar AJ., LSD1-BDNF activity in lateral hypothalamus-medial forebrain bundle area is essential for reward seeking behavior. Progress in Neurobiology 2021; 202:102048 (Impact factor: 11.685) (citations: 6) (ISSN: 0301-0082).
2) Awathale SN., Waghade AK., Kawade HM., Jadhav G., Choudhary AG., Sagarkar S., SakharkarAJ., Subhedar NK., Kokare DM. Neuroplastic changes in the superior colliculus and hippocampus in self-rewarding paradigm: importance of visual cues. Molecular Neurobiology 2021, doi: 10.1007/s12035-021-02597-2 (Impact factor: 5.59)
3) Nagalakshmi B., Sagarkar S., Choudhary A., Kokare D., Sakharkar AJ. Repeated mild traumatic brain injury causes epigenetic silencing of superoxide dismutase 2 in the hippocampus via DNMT3b-mediated DNA methylation. Molecular Neurobiology 2021; 58:1162-1184. (Impact Factor: 5.59) (citations: 4) (ISSN: 0893-7648).
4) Nagalakshmi B., Srivastava A., Pawar N., Sagarkar S., Sakharkar AJ. Repeated mild traumatic brain injury induces persistent variations in mitochondrial DNA copy number in mesocorticolimbic neurocircuitry of the rat. Neuroscience Research 2020;155:34-42. (Impact factor: 3.304) (citations: 5) (ISSN: 0168-0102).
5) Hadawale KN, Sagarkar S, Bhargava SY, Seasonal variation of Neuropeptide Y(NPY) in the brain of frog, Microhyla ornate. Neuroscience Letters 2020;740:135409 (Impact Factor: 3.046) (citations: 4) (ISSN