Browsing by Author "Rakesh Verma"

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Bisphenol S dysregulates thyroid hormone homeostasis; Testicular survival, redox and metabolic status: Ameliorative actions of melatonin
(Elsevier B.V., 2023) Aishwarya Sahu; Rakesh Verma
Bisphenol S (BPS) is an incipient threat for reproductive health augmenting societal burden of infertility worldwide. In the present study, we investigated the mechanism of BPS induced testicular dysfunctions and protective actions of melatonin in mice. BPS (150 mg/kg BW) treatment reduced serum T3/T4, testosterone and elevated insulin levels along with adverse effect on thyroid and testicular histoarchitecture. Further, BPS treatment compromised sperm quality, reduced mRNA expression of steroidogenic (StAR/CYP11A1) markers, elevated oxidative load and disrupts metabolic status. However, melatonin (5 mg/kg BW) administration to BPS treated mice showed improved hormonal/histological parameters, enhanced thyroid hormone (TR-α/Dio-2)/melatonin (MT-1) receptor expressions. Further, melatonin treatment modulated the expression of testicular survival/redox (SIRT1/PGC-1α/FOXO-1, Nrf2/HO-1, p-JAK2/p-STAT3), proliferative (PCNA) and metabolic (IR/pAKT/GLUT-1) markers. Furthermore, melatonin treatment enhanced testicular antioxidant status and reduced caspase-3 expression. In conclusion, our results showed that BPS induces endocrine/oxidative and metabolic anomalies while melatonin improved male reproductive health. © 2023 Elsevier B.V.
BPS-induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT-1/Nrf2/NFĸB and IR/PI3K/pAkt/GLUT-4 expressions in adult golden hamster
(John Wiley and Sons Inc, 2023) Sriparna Pal; Aishwarya Sahu; Rakesh Verma; Chandana Haldar
Ever-increasing occurrence of plastic-manufacturing industries leads to environmental pollution that has been associated with declined human health and increased incidence of compromised reproductive health. Female subfertility/infertility is a complex phenomenon and environmental toxicants as well as lifestyle factors have a crucial role to play. Bisphenol S (BPS) was believed to be a “safer” replacement of bisphenol A (BPA) but recent data documented its neurotoxic, hepatotoxic, nephrotoxic, and reprotoxic attributes. Hence based on the scarcity of reports, we investigated molecular insights into BPS-induced ovarian dysfunction and protective actions of melatonin against it in adult golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin (3 mg/kg BW i.p. alternate days) and BPS (150 mg/kg BW orally every day) for 28 days. BPS treatment disrupted hypothalamo–pituitary–ovarian (HPO) axis as evident by reduced gonadotropins such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), ovarian steroids such as estradiol (E2) and progesterone (P4), thyroid hormones namely triiodothyronine (T3) and thyroxine (T4) and melatonin levels along with their respective receptors (ERα, TRα, and MT-1) thereby reducing ovarian folliculogenesis. BPS exposure also led to ovarian oxidative stress/inflammation by increasing reactive oxygen species and metabolic disturbances. However, melatonin supplementation to BPS restored ovarian folliculogenesis/steroidogenesis as indicated by increased number of growing follicles/corpora lutea and E2/P4 levels. Further, melatonin also stimulated key redox/survival markers such as silent information regulator of transcript-1 (SIRT-1), forkhead box O-1 (FOXO-1), nuclear factor E2-related factor-2 (Nrf2), and phosphoinositide 3-kinase/protein kinase B (PI3K/pAkt) expressions along with enhanced ovarian antioxidant capacity. Moreover, melatonin treatment reduced inflammatory load including ovarian nuclear factor kappa-B (NFĸB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expressions, serum tumor necrosis factor α (TNFα), C-reactive protein (CRP) and nitrite–nitrate levels as well as upregulated ovarian insulin receptor (IR), glucose uptake transporter-4 (GLUT-4), connexin-43, and proliferating cell nuclear antigen (PCNA) expressions in ovary thereby ameliorating inflammatory and metabolic alterations due to BPS. In conclusion, we found severe deleterious impact of BPS on ovary while melatonin treatment protected ovarian physiology from these detrimental changes suggesting it to be a potential preemptive candidate against environmental toxicant-compromised female reproductive health. © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Comprehensive Review on Cervical Cancer: Global Health Burden
(Bentham Science Publishers, 2025) Namra Aziz; Vikrant Abbot; Aishwarya Bajpai; Wal Pranay; Ankita Wal; Rakesh Verma; Mukesh Chandra Sharma
Cervical cancer is one of the four most common cancers that affect women worldwide, along with breast, colorectal, lung, and cervical cancer. It is a major public health concern that mostly affects women. Virtually all cases of cervical cancer are linked to human papillomavirus (HPV) infections. Patients must be screened and immunized to prevent this disease, although developed and developing nations have different rates of cervical cancer incidence. Palliative chemotherapy continues to be the go-to therapy for patients who are not candidates for radiation therapy or curative surgery. To counteract chemotherapy's low effectiveness, other treatment approaches are being developed. The main goals of this review study are to advance knowledge of cervical cancer, promote awareness and educated decision-making, and investigate cutting-edge approaches to the disease's treatment. A literature review was done from databases like Google Scholar, PUBMED-MEDLINE, and Scopus using standard keywords “Cancer,” “Cervical Cancer,” “Human papillomavirus,” “Chemotherapy,” and “Treatment Therapies” from 2010-2023. The Government of India intends to initiate a three-phase vaccination drive against Human Papillomavirus (HPV) for girls aged 9-14, aiming to mitigate the risk of cervical cancer. The vaccine also offers protection against the HPV strains that cause cancer of the anus, vagina, and oropharynx. Although cervical cancer is still a tough foe, we are getting closer to a time when it may be prevented and treated, even in the most underprivileged areas, due to continuous advancements and steadfast dedication. © 2025 Bentham Science Publishers.
Environmental toxicant compromised reproductive health: Rescue by melatonin
(Nova Science Publishers, Inc., 2020) Jitendra Kumar; Sriparna Pal; Shruti R. Hansda; Chandana Haldar; Rakesh Verma
Several factors are responsible for declined male and female reproductive potential such as altered lifestyle, nutritional deficiency, global industrialization and increased exposure to environmental toxicants. The World Health Organization documents that around 15% couples face the problems of infertility but its underlying aetiology and treatment still need to be explored. Increased exposure to environmental toxins impair testicular and ovarian physiology through modulation of metabolic status (IR-GLUTs), redox (SIRT-1/Nrf-2/HO-1), inflammatory (NF-κB/COX-2) and apoptotic (Bax/Bcl-2 ratio, caspase-3) proteins and thus compromises reproductive health. Moreover, environmental contaminants have been reported in human blood, urine and milk. Melatonin, a pineal hormone, controls numerous physiological functions and act as an antioxidant, antiapoptotic, anti-inflammatory molecule in various organisms including human. Extra pineal organs such as retina, cerebellum, gastrointestinal tract and reproductive organs are also the source of melatonin. Within gonads, presence of Aralkylamine N-acetyltransferase (AANAT) and N-acetylserotonin O-methyltransferase (ASMT) convinced the intra gonadal synthesis of melatonin. Further, melatonin receptor (MT-1/2) has been reported in testicular Leydig cells, Sertoli cells, sperm and ovarian granulosa cells of mammals including humans that altogether reinforced its autocrine and paracrine role in regulation of reproductive physiology. Recently, melatonin has been reported to modulate various transcription factors and proteins that controls metabolic status and survival factors such as SIRT-1/Nrf-2 and its downstream signalling pathway in various organs including gonads. Therefore, advancement in melatonin research suggests that it could be use for the treatment of fertility related problems and improve the reproductive health. © 2021 Nova Science Publishers, Inc.
Evaluation of the Effect of Virgin Rice Bran Oil (VRBO) on Doxorubicin-induced Cardiotoxicity in Wistar Rats
(Bentham Science Publishers, 2025) Suseela Prema; Rakesh Verma; Amitesh Nagarwal; Meenakshi Bharkatiya; Madhuri Baghel; Ladli Kishore; Wal Pranay; Amin Gasmi
Introduction: The usage of doxorubicin (DOX), an antineoplastic drug that is frequently used for the cure of cancer, is restricted to maximal doses due to its cardiac toxicity. Reactive oxygen species produced by DOX result in lipid peroxidation and organ failure, ultimately resulting in cardiomyopathy. Due to its high polyphenol content, virgin rice bran oil (VRBO) is a diet nutritional supplement with a strong antioxidant. This study aimed to assess the potential defense of VRBO against DOX-induced cardiotoxicity. Methods: VRBO and DOX injections were administered to thirty male Wistar rats for 42 days after being randomly assigned to five groups. Results: The study demonstrated the cardioprotective effects of VRBO against doxorubicin (DOX)-induced cardiotoxicity. VRBO (0.71 and 1.42 ml/kg) significantly improved the heart-to-body weight ratio, reduced elevated serum CK-MB and LDH levels by 18.4% and 52.7%, respectively, and increased HDL by 43.1%. ECG parameters also improved, with reductions in QT interval (19%), ST interval (28%), and QRS complex (15%). VRBO enhanced systolic blood pressure (up to 21%) and heart rate (7.1%). Antioxidant markers showed notable recovery, with MDA levels reduced by 66.1%, while GSH, SOD, and catalase levels increased by 129.4%, 158.2%, and 84.8%, respectively. Conclusion: A cardioprotective benefit was found at middle and higher VRBO dosages. In order to demonstrate the effectiveness of VRBO as a cardioprotective medication, further research on dosage response and bioavailability is required. © 2025 Bentham Science Publishers.
Expression of receptors for melatonin (MT1), thyroid hormone (TR-α), deiodinase (Dio-2), glucose transporters (GLUT-1 &4) and its relation with splenic cell survival (Bcl-2) of golden hamster, Mesocricetus auratus
(Taylor and Francis Ltd., 2019) Rakesh Verma; Chandana Haldar
Seasonal breeder utilises photoperiod as environmental clue to adjust their energetically demanding phenomenon such as reproduction and immunity by the mechanism of trade-off. The photoperiodic modulation of melatonin (MT-1)-thyroid hormone receptor (TR-α), deiodinase (Dio-2) activity and its interrelationship with glucose transporters (GLUT-1&4) in lymphoid organ of seasonal breeder is lacking that may explain possible role of photoperiod and its relationship with the cell survival factors (Bcl-2) in spleen of golden hamster, Mesocricetus auratus. We reported that photoperiod regulates the circulatory melatonin and thyroid hormone levels. Short-day-induced melatonin can act via MT1 and may enhance the expressions of GLUT-1&4 thereby the energy and cell survival factor (Bcl-2) in spleen. On the other hand, long-day-induced thyroid hormone is converted to bioactive from (T-4 to T3) by action of Dio-2 that acts through TR-α to maintain minimum level of energy for immune responses. In conclusion, present result explains the reason behind the basic molecular events involved in trade-offs mechanism in seasonal variation of immune responses. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
Fluoride Compromises Testicular Redox Sensor, Gap Junction Protein, and Metabolic Status: Amelioration by Melatonin
(Humana Press Inc., 2020) Jitendra Kumar; Chandana Haldar; Rakesh Verma
The excess fluoride intake has been shown to adversely affect male reproductive health. The aim of the present study was to investigate the key mechanism underlying fluoride-induced testicular dysfunction and the role of melatonin as a modulator of testicular metabolic, oxidative, and inflammatory load. The present results indicated that sodium fluoride (NaF) exposure to adult male golden hamsters severely impairs reproductive physiology as evident from markedly reduced sperm count/viability, testosterone level, androgen receptor (AR), testicular glucose transporter (GLUT-1), gap junction (connexin-43), and survival (Bcl-2) protein expression. NaF exposure markedly increased testicular oxidative load, inflammatory (NF-kB/COX-2), and apoptotic (caspase-3) protein expression. However, melatonin treatment remarkably restored testicular function as evident by normal histoarchitecture, increased sperm count/viability, enhanced antioxidant enzyme activities (SOD and Catalase), and decreased lipid peroxidation (LPO) level. In addition, melatonin treatment upregulated testicular Nrf-2/HO-I, SIRT-1/ FOXO-1, and downregulated NF-kB/COX-2 expression. Further, melatonin ameliorated NaF-induced testicular metabolic stress by modulating testicular GLUT-1expression, glucose level, and LDH activity. Furthermore, melatonin treatment enhanced testicular PCNA, Bcl-2, connexin-43, and reduced caspase-3 expression. In conclusion, we propose the molecular mechanism of fluoride-induced testicular damages and ameliorative action(s) of melatonin. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Impact of photoperiod on uterine redox/inflammatory and metabolic status of golden hamster, Mesocricetus auratus
(John Wiley and Sons Inc, 2022) Sriparna Pal; Chandana Haldar; Rakesh Verma
Photoperiod modulates reproductive physiology at multiple levels in seasonally breeding animals. Golden hamsters are long-day breeders that diminish their fertility during the short days. Photoperiod is known to regulate hormonal milieu and uterus is a hormone-sensitive dynamic tissue. However, there is lack of molecular insight regarding the impact of photoperiod on uterine physiology with respect to redox and metabolic status in Mesocricetus auratus. We evaluated the impact of photoperiod on circulatory hormonal parameters (triiodothyronine [T3], thyroxin [T4], estradiol [E2], progesterone [P4], melatonin, and insulin), their receptor expressions and key markers associated with redox (SIRT-1/FOXO-1), inflammatory (NFĸB/COX-2) and metabolic (IR/GLUT4) status in uterus. Adult female golden hamsters were exposed to different photoperiodic regimes, that is, short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. SP drastically decreased peripheral hormone profiles (T3, T4, E2, and P4) and compromised uterine histoarchitecture when compared with LP-exposed hamsters. Further, SP markedly decreased thyroid hormone receptor-α (TRα), insulin receptor, and glucose uptake transporter-4 (GLUT-4) expressions in uterus. We noted enhanced uterine oxidative (increased MDA and decreased SOD/CAT levels), SIRT-1/FOXO-1 expression and inflammatory (NFĸB/COX-2) load in SP condition. Further, elevated levels of circulatory insulin, melatonin, and its receptor (MT-1) expression in uterus was noted under SP condition. Thus, we may suggest that photoperiod might regulate uterine seasonality through modulation of local hormonal and redox/metabolic homeostasis thereby may restrict offspring bearing capacity under short days. © 2022 Wiley Periodicals LLC.
Melatonin alleviates hyperthyroidism induced oxidative stress and neuronal cell death in hippocampus of aged female golden hamster, Mesocricetus auratus
(Elsevier Inc., 2016) Geeta Rao; Rakesh Verma; Arun Mukherjee; Chandana Haldar; Neeraj Kumar Agrawal
Oxidative stress is a well known phenomenon under hyperthyroid condition that induces various physiological and neural problems with a higher prevalence in females. We, therefore investigated the antioxidant potential of melatonin (Mel) on hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain (cognition and memory centre) of aged female golden hamster, Mesocricetus auratus. Aged female hamsters were randomly divided into four experimental groups (n = 7); group-I: control, group-II: Melatonin (5 mg kg− 1 day− 1, i.p., for one week), group-III: Hyperthyroid (100 μg kg− 1 day− 1, i.p., for two weeks) and group-IV- Hyper + Mel. Hormonal profiles (thyroid and melatonin), activity of antioxidant enzymes (SOD, CAT and GPX), lipid peroxidation level (TBARS) and the specific apoptotic markers (Bax/Bcl-2 ratio and Caspase-3) expression were evaluated. A significant increase in the profile of total thyroid hormone (tT3 and tT4) in hyperthyroidic group as compared to control while tT3 significantly decreased in melatonin treated hyperthyroidic group. However, Mel level significantly decreased in hyperthyroidic group but increased in melatonin treated hyperthyroidic group. Further, the number of immune-positive cells for thyroid hormone receptor-alpha (TR-α) decreased in the hippocampus of hyperthyroidic group and increased in melatonin treated hyperthyroidic group. Profiles of antioxidant enzymes showed a significant decrease in hyperthyroidic group with a simultaneous increase in lipid peroxidation (TBARS). Melatonin treatment to hyperthyroidic group lead to decreased TBARS level with a concomitant increase in antioxidant enzyme activity. Moreover, increased expression of Bax/Bcl-2 ratio and Caspase-3, in hyperthyroidic group had elevated neuronal cell death in hippocampal area and melatonin treatment reduced its expression in hyperthyroidic group. Our findings thus indicate that melatonin reduced the hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain, suggesting a novel therapeutic approach of melatonin for management of cognition and memory function in females under hyperthyroid condition. © 2016 Elsevier Inc.
Melatonin ameliorates Bisphenol S induced testicular damages by modulating Nrf-2/HO-1 and SIRT-1/FOXO-1 expressions
(John Wiley and Sons Inc, 2021) Jitendra Kumar; Rakesh Verma; Chandana Haldar
BPS has detrimental effects on human reproductive health and emerged as an environmental contaminant for global health concern. This study deals with the adverse impact of BPS exposure on testicular oxidative stress, inflammation and apoptosis in adult male golden hamster, Mesocricetus auratus and its amelioration by melatonin. BPS (75 mg/kg BW/day) exposure caused testicular impairment as evident by histological degenerative changes, declined sperm quality (viability and motility), serum levels of testosterone and melatonin with a concomitant decrease in testicular androgen receptor (AR) and melatonin receptor (MT1) expression. The BPS exposure caused marked increase in testicular oxidative load, inflammation (NF-kB/COX-2) and apoptosis (caspase-3). Melatonin (10 mg/kg BW/alternate day) pretreatment to BPS exposed hamsters resumed normal testicular histoarchitecture, sperm quality and decreased testicular oxidative load as evident by enhanced antioxidant enzymes (SOD and catalase) activities and decreased lipid peroxidation (LPO) level. Further, melatonin also stimulated the testicular antioxidant proteins Nrf-2/HO-1, SIRT-1/FOXO-1 and reduced inflammatory proteins NF-kB/COX-2 expression to counteract BPS induced testicular damages. Melatonin administration to the BPS treated hamsters resulted in increased testicular cell proliferation (PCNA), survival (Bcl-2), gap junction (connexin-43) and decreased apoptosis (caspase-3). In conclusion, our study documented the detrimental effects of BPS on testes that compromises male fertility. Further, melatonin was found as a potent molecule that rescued the BPS induced testicular damages in male golden hamster Mesocricetus auratus. © 2020 Wiley Periodicals LLC.
Melatonin Ameliorates LPS-Induced Testicular Nitro-oxidative Stress (iNOS/TNFα) and Inflammation (NF-kB/COX-2) via Modulation of SIRT-1
(Springer Science and Business Media Deutschland GmbH, 2021) Jitendra Kumar; Chandana Haldar; Rakesh Verma
Lipopolysaccharide (LPS) — an endotoxin that is being extensively used in laboratory to mimic microbial infection that adversely affects male fertility. This study investigated the protective effects of melatonin on LPS-induced testicular nitro-oxidative stress, inflammation, and associated damages in the testes of male golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin and LPS for 7 days. Testes of LPS treated hamsters showed degenerative changes (appearance of vacuoles, exfoliation, and depletion of germ cells in the seminiferous tubules), adverse effects on spermatogenesis (sperm count and viability), and steroidogenesis (declined serum and testicular testosterone). Furthermore, LPS treatment decreased melatonin content, melatonin receptor (MT1), and antioxidant potential (catalase and SOD), and simultaneously increased nitro-oxidative stress (CRP, nitrate, TNFα). LPS upregulated NF-kB, COX-2, and iNOS expressions to increase testicular inflammatory load that resulted in the decrease of germ cell proliferation and survival, thus culminating into germ cell apoptosis as indicated by AO-EB staining and caspase-3 expression. Administration of melatonin with LPS showed improved testicular histoarchitecture, sperm parameters, and testosterone level. Melatonin increased testicular antioxidant status (SOD, catalase) to counteract the LPS-induced testicular ROS and thus reduced testicular nitro-oxidative stress. Furthermore, melatonin treatment upregulated testicular SIRT-1 expression to inhibit LPS-induced inflammatory proteins, i.e., NF-kB/COX-2/iNOS expression. The rescue effect of melatonin was further supported by increased germ cell survival (Bcl-2), proliferation (PCNA), and declined apoptosis (caspase-3). In conclusion, our result demonstrated that melatonin rescued testes from LPS-induced testicular nitro-oxidative stress, inflammation, and associated damages by upregulation of SIRT-1. © 2021, Society for Reproductive Investigation.
Melatonin attenuates LPS-induced ovarian toxicity via modulation of SIRT-1, PI3K/pAkt, pErk1/2 and NFĸB/COX-2 expressions
(Academic Press Inc., 2022) Sriparna Pal; Chandana Haldar; Rakesh Verma
The association between inflammation and metabolic disturbances leads to various female pathophysiological conditions. Bacterial lipopolysaccharide (LPS), found in the outer membrane of gram-negative bacteria, elicits an oxidative and inflammatory response that profoundly interferes with female reproductive health. We investigated the ameliorative action of melatonin on LPS-induced ovarian pathophysiology in golden hamsters, Mesocricetus auratus. Hamsters were administered with exogenous melatonin (5 mg/kg BW) and LPS (100 μg/kg BW) intraperitoneally for 7 days. LPS treatment impaired ovarian folliculogenesis as evident by histoarchitecture (elevated number of atretic follicles, reduced number of growing follicles and corpus luteum) and steroidogenesis (decreased aromatase/ERα, estradiol and progesterone). On the other hand, LPS administration also perturbed thyroid hormone (T3 and T4) homeostasis, ovarian melatonin receptor (MT-1) expression, antioxidant potential (SOD and catalase) and concomitantly elevated nitro-oxidative stress (decreased SOD, catalase and elevated CRP, TNFα and nitrate/nitrite level) and inflammatory load (NFĸB and COX-2) which culminated into ovarian follicular apoptosis (elevated caspase-3). LPS also disrupted metabolic homeostasis as indicated by hyperinsulinemia with a simultaneous decrease in ovarian IR/GLUT-4 and glucose content. Moreover, LPS treatment decreased expressions of key markers of ovarian physiology (SIRT-1, pErk1/2, PI3K and pAkt). Melatonin co-treatment with LPS improve these detrimental changes proposing melatonin as a potent therapeutic candidate against ovarian dysfunction induced by endotoxin. © 2022 Elsevier Inc.
Melatonin Improves Lactational Bisphenol S Induced Pre-Pubertal and Pubertal Testicular Impairments in Offspring
(Springer Nature, 2025) Aishwarya Sahu; Vartika Malik; Rakesh Verma
Lactational period is of extreme importance for nourishing and fostering growth in neonates. Bisphenol S (BPS) a congener of bisphenol A (BPA) is an emerging environmental toxicant reported to have deleterious effects on reproductive health. Indirect exposure of BPS to the suckling infants via breastmilk is less explored although it can lead to various public health issues. Therefore, we investigated harmful effects of lactational BPS exposure on pre-pubertal and pubertal testicular functions of the offspring and its possible amelioration by melatonin. Lactating dams were divided into 4 groups: control, melatonin treated (3 mg/kg BW), BPS treated (150 mg/kg BW) and BPS + melatonin co-treatment; the male offspring were evaluated at pre-pubertal (PND 22) and pubertal (PND 42) testicular developmental stages. Lactational BPS exposure affected testicular physiology, led to histological abnormalities, hormonal imbalance, alters blood-testis-barrier (E-cadherin/connexin-43), redox modulators (SIRT-1/FOXO-1/PGC-1α; Nrf2/HO-1/pSTAT-3) and germ cell dynamicity (PCNA/TUNEL positive cells) in both pre-pubertal and pubertal mice. However, melatonin supplementation to BPS exposed lactating mothers improved testicular histoarchitecture in offspring, enhanced testicular antioxidant status, modulated expression of redox/survival and BTB markers that promoted germ cell proliferation. In conclusion, our study shows that lactational BPS exposure could be deleterious to testicular physiology that may result in male infertility/subfertility in later life while melatonin supplementation improves the reproductive health compromised by lactational BPS exposure. © The Author(s), under exclusive licence to Society for Reproductive Investigation 2025.
Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches
(Elsevier Inc., 2025) Spandana Rajendra Kopalli; Tapan Behl; Lalji H. Baldaniya; Suhas Ballal; Kamal K. Joshi; Renu Arya; Bhumi Chaturvedi; Ashish Singh Chauhan; Rakesh Verma; Minesh Patel; Sanmati Kumar Jain; Ankita Wal; Monica Gulati; Sushruta Koppula
Progressive neuronal loss is a hallmark of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS), which cause cognitive and motor impairment. Delaying the onset and course of symptoms is largely dependent on neuroadaptation, the brain's ability to restructure in response to damage. The molecular, cellular, and systemic processes that underlie neuroadaptation are examined in this study. These mechanisms include gliosis, neurogenesis, synaptic plasticity, and changes in neurotrophic factors. Axonal sprouting, dendritic remodelling, and compensatory alterations in neurotransmitter systems are important adaptations observed in NDDs; nevertheless, these processes may shift to maladaptive plasticity, which would aid in the advancement of the illness. Amyloid and tau pathology-induced synaptic alterations in Alzheimer's disease emphasize compensatory network reconfiguration. Dopamine depletion causes a major remodelling of the basal ganglia in Parkinson's disease, and non-dopaminergic systems compensate. Both ALS and Huntington's disease rely on motor circuit rearrangement and transcriptional dysregulation to slow down functional deterioration. Neuroadaptation is, however, constrained by oxidative stress, compromised autophagy, and neuroinflammation, particularly in elderly populations. The goal of emerging therapy strategies is to improve neuroadaptation by pharmacologically modifying neurotrophic factors, neuroinflammation, and synaptic plasticity. Neurostimulation, cognitive training, and physical rehabilitation are instances of non-pharmacological therapies that support neuroplasticity. Restoring compensating systems may be possible with the use of stem cell techniques and new gene treatments. The goal of future research is to combine biomarkers and individualized medicines to maximize neuroadaptive responses and decrease the course of illness. In order to reduce neurodegeneration and enhance patient outcomes, this review highlights the dual function of neuroadaptation in NDDs and its potential as a therapeutic target. © 2024
Photoperiod modulates oestrogen status, insulin interposed glucose uptake and connexin-43 in testes of golden hamster, Mesocricetus auratus
(Taylor and Francis Ltd., 2020) Sriparna Pal; Rakesh Verma; Jitendra Kumar; Chandana Haldar
The environmental photoperiod plays an important role in regulation of seasonal reproductive events. However, with reference tooestrogen status the exact mechanism involved in testicular seasonality is still unclear in general and especially in long-day breeder golden hamster, Mesocricetus auratus. Therefore, in the present study we explored the effect of day length (long day, LD and short day, SD) in modulation of oestrogen level, metabolic and gap junction markers expressionin testes. Our results suggest that LD exposureinduced normal testicular activity as evident by histoarchitectural analyses showing different stages of spermatogenesis, spermatozoa filled lumen and normal Leydig cells. Furthermore, LD upregulated testicular metabolic parameters such as IR, GLUT-8, glucose leveland LDH activity along with predominant testicular gap junction protein (Connexin-43) expression as compared to SD. On the other hand, the expressions of ER-α, aromatase and caspase-3 were reduced under LD condition as compared to SD. Thus, it can be inferred that photoperiod modulates the circulatoryoestrogen level, along with gap junction protein and apoptosis markers expression in testes and harmonizes the energy homeostasis involved in reproductive maintenance for seasonality of golden hamster. Therefore, we may conclude that day-length-mediatedoestrogen is a prominent modulator of male reproductive health. Abbreviations: Insulin receptor (IR); Glucose uptake transporter-8 (GLUT-8); Estrogen receptor-alpha (ER-α); Connexin-43 (Cxn-43); Lactate dehydrogenase (LDH). © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
Photoperiodic modulation of ovarian metabolic, survival, proliferation and gap junction markers in adult golden hamster, Mesocricetus auratus
(Elsevier Inc., 2022) Sriparna Pal; Chandana Haldar; Rakesh Verma
Female reproductive physiology is greatly dependent on tight regulation of metabolic and survival factors. Photoperiod regulates female reproductive rhythms but very less information exists explaining whether photoperiod could modulate thyroid hormone homeostasis, metabolic/energy parameters along with survival, proliferation and gap junction proteins in the ovary of a long-day breeder, Mesocricetus auratus. Adult female hamsters were exposed to different photoperiodic regimes i.e., critical photoperiod (CP; 12.5L:11.5D), short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. LP upregulated thyroidal and gonadal activity as apparent by histoarchitecture, thyroid hormone profile [triiodothyronine (T3), thyroxin (T4) and thyroid stimulating hormone (TSH)], luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P4) levels when compared with SP exposed hamsters. Further, LP increased thyroid hormone receptor-α/deiodinase-2 (TRα/Dio-2), estrogen receptor-α (ERα)/aromatase and insulin receptor/glucose transporter-4 (IR/GLUT-4) expressions in ovary. Interestingly, ovarian sirtuin-1 (SIRT-1) expression was also upregulated under LP condition along with cell proliferation (proliferating cell nuclear antigen or PCNA), survival (B cell lymphoma-2 or Bcl-2) and gap junction (connexin-43) markers when compared to SP exposed hamsters. We also noted elevated levels of circulatory leptin, insulin along with melatonin and its receptor (MT-1) in ovary under SP condition. Thus, we suggest that photoperiod plays a vital role in regulation of thyroid and reproductive hormone homeostasis along with key metabolic and survival markers in the ovary of adult golden hamsters, M. auratus providing further insight into the regulation of female reproductive seasonality in a long-day breeder. © 2021 Elsevier Inc.
Photoperiodic modulation of thyroid hormone receptor (TR-α), deiodinase-2 (Dio-2) and glucose transporters (GLUT 1 and GLUT 4) expression in testis of adult golden hamster, Mesocricetus auratus
(Elsevier B.V., 2016) Rakesh Verma; Chandana Haldar
Phenomenon of seasonal reproduction is being regulated by changes in day length or photoperiod. The molecular mechanism underlying the event of photoperiodic regulation of testis and thyroid functions along with glucose uptake transporters has never been reported for golden hamster, M. auratus. The present study was performed to investigate the effect of photoperiod on the expression of key thyroid hormone receptor (TR-α), deiodinase-2 (Dio-2) and glucose uptake transporters (GLUT-1 & GLUT-4) in testicular germ cell and Leydig cells, and its correlation with the testicular androgen receptor (AR), germ cell proliferation factor (PCNA) and cell survival factor (Bcl-2) in testis of adult golden hamster, Mesocricetus auratus. Hamsters were exposed to different photoperiodic regimes i.e. critical photoperiod (CP), short day (SD) and long day (LD) for 10 weeks. LD induces upregulation of thyroidal and gonadal activity as evident by active thyroid gland and testicular histoarchitecture, peripheral total thyroid (tT3, tT4) and testosterone hormone profiles when compared with SD exposed hamsters. Further, LD increased the expression of testicular TR-α, Dio-2, GLUT-1, GLUT-4 along with testicular AR and glucose content thereby enhancing germ cell proliferation and survival as reflected by increased PCNA and Bcl-2 expression when compared to SD exposed hamsters. Thus, it can be suggested that testicular thyroid hormone status is being regulated by photoperiod and is possibly involved in seasonal adaptation to reproductive phenomenon of golden hamster. © 2016 Elsevier B.V.
Seasonal Reproductive Strategies of Indian Palm Squirrel, Funambulus pennanti: Modulation by Climate, Pineal Gland and Melatonin
(Springer Nature, 2025) Chandana Haldar; Sameer Gupta; Rakesh Verma; Vartika Malik
Rhythmic environmental changes caused by planetary movements are responsible for the evolution of life on Earth. Environmental and climatic variations prepare the animals to adapt themselves to the changing conditions accordingly. These changes in the environment ensure the most essential events occur optimally just once in a year, e.g. seasonal reproduction, hibernation, fur-colour change, etc., or at a particular time of day, e.g. sleep-wake, activity-rest cycle, etc. Seasonality in reproduction is an essential component of the life cycle for the perpetuation of species and is also the primary physiological phenomenon that is frequently and repeatedly being studied. It is among the major components of the “complex web” of seasonal physiological adjustments that permit organisms to protect their progeny and maintain a positive energy balance throughout the fluctuating ambient seasonal temperature and food availability in challenging environmental settings. © 2025 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
Therapeutic aspects of melatonin in bone marrow and thyroid associated immune regulation
(Nova Science Publishers, Inc., 2017) Shraddha Rastogi; Rakesh Verma; Chandana Haldar
The immune system is functionally compartmentalized and is collectively modulated by various internal factors such as hormones, cytokines and externally by seasonal variations in day-length. Neuro-hormone melatonin serves as a "Timezyme" (marker of day-length variation) and a connecting link between the neuro-immuno-endocrine circuits. The role of melatonin in regulating immune functions is well documented. Previous studies have reported that the process of hematopoiesis is regulated by the peripheral levels of melatonin as well as the melatonin synthesized within the microenvironment of bone marrow. The bone marrow granulocyte macrophage colony forming cells (CFU-GM) rhythmically proliferates during the dark hours coinciding with the higher circulatory levels of melatonin. Melatonin acts through its highly specific receptor MT1 present on the surface of progenitor immuno-competent cells (B- and T-cells). Literature suggests that the thyroid hormone(s) also play a key role in regulation of immune functions by acting on immuno-competent cells through its receptor TR-a. Altered thyroid status is responsible for imbalances in antioxidant-pro-oxidant level in lymphoid organs. Melatonin being a well-known endogenous antioxidant effectively combats oxidative stress in lymphoid tissues induced by altered thyroid hormones. Most of evidences exist supporting that melatonin influences CFU-GM function. How the thyroid gland dysfunction influences immune status and bone marrow CFU-GM function is a question for neuro-endocrinologists as melatonin and thyroid hormone both influences immunity. The review encompasses the role of melatonin in regulation of bone marrow function and thyroid function whose interaction is finally responsible in regulation of immunity in normal and clinical conditions. These interactions can be easily judged by the expression of MT1 and TR-a in lymphoid organ which can throw a light in multifarious hypothesis of immune regulation to explain various clinical challenges. Thus, having diverse beneficial functions melatonin could be a potent therapeutic agent to treat the immuno-compromised state of an individual. © 2017 Nova Science Publishers, Inc.