Browsing by Author "Ishan Kumar Patro"

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Early life exposure to poly I:C impairs striatal DA-D2 receptor binding, myelination and associated behavioural abilities in rats
(Elsevier B.V., 2021) Brijendra Singh; Yogesh Kumar Dhuriya; Nisha Patro; Mahendra Kumar Thakur; Vinay Kumar Khanna; Ishan Kumar Patro
Early-life viral infections critically influence the brain development and have been variously reported to cause neuropsychiatric diseases such as Schizophrenia, Parkinson's diseases, demyelinating diseases, etc. To investigate the alterations in the dopaminergic system, myelination and associated behavioral impairments following neonatal viral infection, the viral immune activation model was created by an intraperitoneal injection of Poly I:C (5 mg/kg bw/ip) to neonatal rat pups on PND-7. The DA-D2 receptor binding was assessed in corpus striatum by using 3H-Spiperone at 3, 6 and 12 weeks of age. MOG immunolabelling was performed to check myelination stature and myelin integrity, while corpus callosum calibre was assessed by Luxol fast blue staining. Relative behavioral tasks i.e., motor activity, motor coordination and neuromuscular strength were assessed by open field, rotarod and grip strength meter respectively at 3, 6 and 12 weeks of age. Following Poly I:C exposure, a significant decrease in DA-D2 receptor binding, reduction in corpus callosum calibre and MOG immunolabelling indicating demyelination and a significant decrease in locomotor activity, neuromuscular strength and motor coordination signify motor deficits and hypokinetic influence of early life viral infection. Thus, the findings suggest that early life poly I:C exposure may cause demyelination and motor deficits by decreasing DA-D2 receptor binding affinity. © 2021 Elsevier B.V.
Poly (I:C) Exposure in Early Life Alters Methylation of DNA and Acetylation of Histone at Synaptic Plasticity Gene Promoter in Developing Rat Brain Leading to Memory Impairment
(SAGE Publications Inc., 2019) Meghraj Singh Baghel; Brijendra Singh; Nisha Patro; Vinay Kumar Khanna; Ishan Kumar Patro; Mahendra Kumar Thakur
Background: Exposure to adverse environmental conditions such as toxic chemicals, viral infections, and even stress during pregnancy or early life may disrupt the development of normal brain and its functioning leading to incidence of neurodevelopmental disorders at later stages of life. Recently, we reported that poly (I:C) exposure altered synaptic plasticity protein level and impaired memory through activation of microglia cells. Purpose: As epigenetic modifications are involved in memory formation, we have studied methylation of DNA and acetylation of histone at promoters of synaptic plasticity genes in the brain of rats exposed to poly (I:C) during early life. Methods: One dose of poly (I:C) (5 mg/kg bw) was intraperitoneally injected to rat pups on postnatal seventh day. A set of pups exposed to vehicle was included as control. In order to assess methylation of DNA and acetylation of histone at synaptic plasticity gene promoter, we performed qPCR after methylated DNA immunoprecipitation and chromatin immunoprecipitation. Results: Poly (I:C) exposure reduced the level of 5-methylcytosine (5mC) at synaptic plasticity gene (bdnf, arc, and egr1) promoters in the frontal cortex (FC) and hippocampus of 3-week rats, although increased it later in both regions of 12-week rats as compared to respective controls. On contrary, poly (I:C) exposure enhanced acetylation of histone H3K9 (H3K9Ac) at promoters of these genes in both regions of 3-week rats but decreased in 12-week rats. Conclusion: Poly (I:C) exposure altered 5mC and H3K9Ac at synaptic plasticity gene promoters resulting in memory impairment of rats at later life. © 2020 Indian Academy of Neurosciences (IAN).
Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain
(Academic Press Inc., 2018) Meghraj Singh Baghel; Brijendra Singh; Yogesh Kumar Dhuriya; Rajendra Kumar Shukla; Nisha Patro; Vinay Kumar Khanna; Ishan Kumar Patro; Mahendra Kumar Thakur
Viral infection during early stage of life influences brain development and results in several neurodevelopmental disorders such as schizophrenia, autism and behavioral abnormalities. However, the mechanism through which infection causes long-term behavioral defects is not well known. To elucidate this, we have used synthetic polyinosinic-polycytidylic acid [poly (I:C)] which acts as a dsRNA molecule and interacts with toll-like receptor-3 (TLR-3) of microglia cells to evoke the immune system, thus mimicking the viral infection. Rat pups of postnatal day (PND) 7 were infused with a single dose of poly (I:C) (5 mg/kg BW) and vehicle alone to controls. When these pups grew to 3, 6 and 12 weeks, their spatial and fear conditioning memory were impaired as assessed by Morris water maze and passive avoidance test, respectively. We checked the immune activation by staining of TNF-α in the hippocampus and observed that poly (I:C) exposure elevated the number of TNF-α positive cells immediately after 12 h of infusion in one week rat and it persisted up to postnatal age of 3 and 12 weeks. Moreover, poly (I:C) significantly decreased the binding of 3H-QNB to the cholinergic receptors in the frontal cortex and hippocampus of 3 and 6 weeks rats as compared to control but did not change significantly in 12 weeks rats. RT-PCR and immunoblotting results showed that poly (I:C) exposure upregulated the expression of memory associated genes (BDNF, Arc, EGR1) at mRNA and protein level in frontal cortex and hippocampus of 3 weeks rats as compared to control. However, long-time persistence of poly (I:C) effects significantly decreased the expression of these genes in both brain regions of 12 weeks rats. Taken together, it is evident that early life exposure to poly (I:C) has a long-term effect and impairs learning and memory, probably through TNF-α mediated neuroinflammation and alteration in the expression of memory associated genes in frontal cortex and hippocampus of rats. © 2018 Elsevier Inc.