Browsing by Author "Shambhu Kumar Prasad"

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Correction to: Investigating cognitive impairments and hippocampal proteome alterations in aged male rats with TAA-Induced minimal hepatic encephalopathy (Biogerontology, (2025), 26, 1, (30), 10.1007/s10522-024-10158-y)
(Springer Science and Business Media B.V., 2025) Vishal Vikram Singh; Shambhu Kumar Prasad; Arup Acharjee; Sanjeeva Srivastava; Papia Acharjee
In the original version of the article, one of the author “Arup Acharjee” should have been denoted as a Co-corresponding author.”, hence it has been corrected. The name was displayed correctly in all versions at the time of publication. The original article has been corrected. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.
Elucidating hippocampal proteome dynamics in moderate hepatic encephalopathy rats: insights from high-resolution mass spectrometry
(Springer Science and Business Media Deutschland GmbH, 2024) Shambhu Kumar Prasad; Vishal Vikram Singh; Arup Acharjee; Papia Acharjee
Hepatic encephalopathy (HE) is a debilitating neurological disorder associated with liver failure and characterized by impaired brain function. Decade-long studies have led to significant advances in our understanding of HE; however, effective therapeutic management of HE is lacking, and HE continues to be a significant cause of morbidity and mortality in patients, underscoring the need for continued research into its pathophysiology and treatment. Accordingly, the present study provides a comprehensive overview aimed at elucidating the molecular underpinnings of HE and identifying potential therapeutic targets. A moderate-grade HE model was induced in rats using thioacetamide, which simulates the liver damage observed in patients, and its impact on cognitive function, neuronal arborization, and cellular morphology was also evaluated. We employed label-free LC–MS/MS proteomics to quantitatively profile hippocampal proteins to explore the molecular mechanism of HE pathogenesis; 2175 proteins were identified, 47 of which exhibited significant alterations in moderate-grade HE. The expression of several significantly upregulated proteins, such as FAK1, CD9 and Tspan2, was further validated at the transcript and protein levels, confirming the mass spectrometry results. These proteins have not been previously reported in HE. Utilizing Metascape, a tool for gene annotation and analysis, we further studied the biological pathways integral to brain function, including gliogenesis, the role of erythrocytes in maintaining blood–brain barrier integrity, the modulation of chemical synaptic transmission, astrocyte differentiation, the regulation of organ growth, the response to cAMP, myelination, and synaptic function, which were disrupted during HE. The STRING database further elucidated the protein‒protein interaction patterns among the differentially expressed proteins. This study provides novel insights into the molecular mechanisms driving HE and paves the way for identifying novel therapeutic targets for improved disease management. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
Investigating cognitive impairments and hippocampal proteome alterations in aged male rats with TAA-Induced minimal hepatic encephalopathy
(Springer Science and Business Media B.V., 2025) Vishal Vikram Singh; Shambhu Kumar Prasad; Arup Acharjee; Sanjeeva Srivastava; Papia Acharjee
The aging population faces a gradual decline in physical and mental capacities, with an increased risk of liver cirrhosis and chronic liver diseases leading to hepatic encephalopathy (HE). The intertwining of physiological manifestations of aging with the pathophysiology of HE significantly impairs cognitive ability, reduces quality of life, and increases mortality. Hence, effective therapeutic intervention is imperative. The present study investigated the impact of minimal HE (MHE) on cognitive impairment in an aged rat population by analyzing hippocampal proteome dynamics. For this purpose, an old MHE rat model was induced via thioacetamide. The label-free LC‒MS/MS method was employed to explore hippocampal proteomic changes and associated dysregulated biological pathways. A total of 1533 proteins were identified, and among these, 30 proteins were significantly differentially expressed (18 upregulated, and 12 downregulated). Three upregulated proteins, namely, fetuin-A, p23, and intersectin-1 were selected and validated for their increased expression via western blotting and immunofluorescence analysis, which confirmed the mass spectrometry results. These proteins have not been reported previously in MHE cases. We also identified the possible dysregulated biological pathways associated with the differentially expressed proteins via Metascape, a network analysis tool. We found that the differentially expressed proteins may be involved in the generation of precursor metabolites and energy, the neurotransmitter release cycle, positive regulation of dendritic spine development, chaperone-mediated protein folding and protein stabilization. This study highlights the potential mechanisms underlying neurological dysfunction in the aged population with MHE and identifies novel therapeutic targets for improved disease management. © The Author(s), under exclusive licence to Springer Nature B.V. 2024.
Microbiota dysbiosis impact on the immune system dysregulation in Huntington's disease (HD)
(Academic Press Inc., 2025) Papia Acharjee; Shambhu Kumar Prasad; Vishal Vikram Singh; Mukulika Ray; Arup Acharjee
Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric impairments caused by Huntingtin (HTT) gene mutations, resulting in the mutant huntingtin (mHTT) protein. Both innate and adaptive immunities play crucial roles in the pathogenesis of HD. In this chapter, we explore the vital role of the gut microbiota in HD, emphasizing its impact on the immune response and brain health via the gut-brain axis. Dysbiosis influences immune responses and HD pathogenesis through microbial metabolites such as short-chain fatty acids (SCFAs) and pathogen-associated molecular patterns (PAMPs). We discuss advanced mathematical models, telemedicine, and biosensors for tracking HD progression and detecting gut dysbiosis. Nutritional interventions to restore microbiota balance and using artificial intelligence and machine learning to predict disease prognosis and personalized treatments have been highlighted. Based on their unique immune profiles and gut microbiota, personalized medicine has been proposed as a promising strategy for effective HD treatment. © 2025
Modulation of brain energy metabolism in hepatic encephalopathy: impact of glucose metabolic dysfunction
(Springer, 2024) Shambhu Kumar Prasad; Arup Acharjee; Vishal Vikram Singh; Surendra Kumar Trigun; Papia Acharjee
Cerebral function is linked to a high level of metabolic activity and relies on glucose as its primary energy source. Glucose aids in the maintenance of physiological brain activities; as a result, a disruption in metabolism has a significant impact on brain function, launching a chain of events that leads to neuronal death. This metabolic insufficiency has been observed in a variety of brain diseases and neuroexcitotoxicity disorders, including hepatic encephalopathy. It is a significant neurological complication that develops in people with liver disease, ranging from asymptomatic abnormalities to coma. Hyperammonemia is the main neurotoxic villain in the development of hepatic encephalopathy and induces a wide range of complications in the brain. The neurotoxic effects of ammonia on brain function are thought to be mediated by impaired glucose metabolism. Accordingly, in this review, we provide an understanding of deranged brain energy metabolism, emphasizing the role of glucose metabolic dysfunction in the pathogenesis of hepatic encephalopathy. We also highlighted the differential metabolic profiles of brain cells and the status of metabolic cooperation between them. The major metabolic pathways that have been explored are glycolysis, glycogen metabolism, lactate metabolism, the pentose phosphate pathway, and the Krebs cycle. Furthermore, the lack of efficacy in current hepatic encephalopathy treatment methods highlights the need to investigate potential therapeutic targets for hepatic encephalopathy, with regulating deficient bioenergetics being a viable alternative in this case. This review also demonstrates the importance of the development of glucose metabolism-focused disease diagnostics and treatments, which are now being pursued for many ailments. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
Signaling Pathways and Gut–Brain Axis: Relationship in Neurological Disorders
(CRC Press, 2025) Papia Acharjee; Vishal Vikram Singh; Shambhu Kumar Prasad; Priyanka Thakur; Arup Acharjee
This chapter looks at the intricate signaling networks associated with the gut–brain axis (GBA) and neurological disorders. The complex, two-way communication system known as the GBA connects the central nervous system (CNS) with the gastrointestinal tract (GIT) via neuronal, immunological, endocrine, and microbial pathways. This chapter delves into the several processes that underlie the GBA, including the vagus nerve, the enteric nervous system (ENS), the autonomic nervous system (ANS), and the role of gut microbiota in influencing neurological illnesses through gut–brain communication via cytokines, metabolites, hormones, and other factors. It draws attention to the connection between gut dysbiosis and neurological diseases like Huntington’s, Parkinson’s, Alzheimer’s, multiple sclerosis, anxiety, depression, and autism spectrum disorders. The chapter also discusses several treatment approaches that target the GBA for the management and prevention of certain neurological illnesses, including probiotics, prebiotics, dietary changes, pharmacological therapy, and fecal microbiota transplantation. The chapter concludes with a review of future research directions, challenges to be faced, and strategies for examining the GBA and its importance for neurological health. © 2026 selection and editorial matter, Neeraj Mishra, Sumel Ashique and Mithun Bhowmick; individual chapters, the contributors.