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Article ; Online: Mutations associated with autism lead to similar synaptic and behavioral alterations in both sexes of male and female mouse brain

Manish Kumar Tripathi / Shashank Kumar Ojha / Maryam Kartawy / Igor Khaliulin / Wajeha Hamoudi / Haitham Amal

Scientific Reports, Vol 14, Iss 1, Pp 1-

2024 Volume 10

Abstract: Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder based on synaptic abnormalities. The estimated prevalence rate of male individuals diagnosed with ASD prevails over females is in a proportion of 4:1. Consequently, males remain the ...

Abstract	Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder based on synaptic abnormalities. The estimated prevalence rate of male individuals diagnosed with ASD prevails over females is in a proportion of 4:1. Consequently, males remain the main focus in ASD studies in clinical and experimental settings. Meanwhile, some studies point to an underestimation of this disorder in females. In this work, we studied the sex differences of the synaptic and behavioral phenotypes of ASD mouse models. Juvenile male and female Shank3Δ4–22 and Cntnap2−/− mutant mice and their WT littermates were used in the experiments. The animals were subjected to a Three-Chamber Sociability Test, then euthanized, and the whole cortex was used for the evaluation of the synaptic phenotype. Protein levels of glutamatergic (NR1) and GABAergic (GAD1 and VGAT) neuronal markers were measured. Protein level of synaptophysin (Syp) was also measured. Dendritic spine density in somatosensory neurons was analyzed by Golgi staining methods. Spine Density and GAD1, NR1, VGAT, and Syp levels were significantly reduced in Shank3Δ4–22 and Cntnap2−/− mice compared to the control group irrespective of sex, indicating impaired synaptic development in the mutant mice. These results were consistent with the lack of differences in the three-chamber sociability test between male and female mice. In conclusion, female ASD mice of both mutations undergo similar synaptic aberrations as their male counterparts and need to be studied along with the male animals. Finally, this work urges the psychiatry scientific community to use both sexes in their investigations.
Keywords	Medicine ; R ; Science ; Q
Subject code	590
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of the sex steroids mediated modulation of leucocyte immune responses in an ophidian Natrix piscator

Alka Singh / Ramesh Singh / Manish Kumar Tripathi

Current Research in Physiology, Vol 5, Iss , Pp 355-

2022 Volume 360

Abstract: The immune-suppressive role of sex steroids in mammals is well documented, but information on other vertebrates is limited. The present study was planned to analyze the effect of testosterone and progesterone in the modulation of immune functions of ... ...

Abstract	The immune-suppressive role of sex steroids in mammals is well documented, but information on other vertebrates is limited. The present study was planned to analyze the effect of testosterone and progesterone in the modulation of immune functions of leucocytes in a reptile, Natrix piscator. Reptiles are unique organisms and this study is novel in that it provides an insight into immune-reproductive cross-talk in a reptile. Leucocytes were isolated from peripheral blood, cultured with different concentrations of testosterone and progesterone and different immune parameters like phagocytosis, superoxide production, and nitrite release were assessed. Lymphocytes were isolated and cell-mediated immunity was assessed through proliferation responses utilizing tetrazolium salt. Concentration-dependent suppressive effects of both the steroids on immune responses were observed. A differential suppressive effect of testosterone was also observed when a lymphocyte proliferation assay was studied. Using receptor antagonists such as cyproterone acetate and mifepristone restored the immune responses of cultured cells. It was summarized that gonadal steroids mediate a direct suppressive effect on innate and cell-mediated immune responses of blood immune cells. It was concluded that when gonadal steroids are high in reproductive seasons, the immune functions are suppressed to gain optimum reproductive success.
Keywords	Testosterone ; Progesterone ; Immune responses ; Proliferation ; Snake ; Physiology ; QP1-981 ; Specialties of internal medicine ; RC581-951
Subject code	570 ; 610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Seasonal Immune Rhythms of head kidney and spleen cells in the freshwater Teleost, Channa punctatus

Rakesh Kumar Chandra / Ajay Kumar Bhardwaj / Atanu Kumar Pati / Manish Kumar Tripathi

Fish and Shellfish Immunology Reports, Vol 5, Iss , Pp 100110- (2023)

2023

Abstract: Annual rhythms in immune function are the reflection of a crucial physiological strategy to deal with environmental stressors. The fish are pivotal animal models to study the annual rhythm and to understand the evolution of the vertebrate biological ... ...

Abstract	Annual rhythms in immune function are the reflection of a crucial physiological strategy to deal with environmental stressors. The fish are pivotal animal models to study the annual rhythm and to understand the evolution of the vertebrate biological system. The current research was planned to assess the annual changes in the innate immune functions of immune cells in a teleost, Channa punctatus. Head kidney and splenic macrophage phagocytosis, superoxide generation, and nitrite release were evaluated to assess innate immunity. Cell-mediated immunity was measured through head kidney and splenic lymphocyte proliferation in presence of mitogens. The superoxide anion generation by the cells of head kidney and spleen was maximum in October. A bimodal pattern in nitrite production was observed with the first peak in November and the second in March. Cosinor analysis revealed a statistically significant annual rhythm in nitrite production. Similarly, phagocytosis and lymphocyte proliferation also showed statistically significant annual rhythms. It was concluded that animals maintain an optimum immune response in seasonally changing environments. Elevated immunity during certain times of the year might assist animals deal with seasonal environmental stressors. Further research may be focused upon measuring survival rate and reproductive success after season induced elevated immunity.
Keywords	Rhythmicity ; Immunity ; Phagocytosis ; Channa punctatus ; Lymphocyte proliferation ; Zoology ; QL1-991
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Photoperiodic manipulation modulates the innate and cell mediated immune functions in the fresh water snake, Natrix piscator

Alka Singh / Ramesh Singh / Manish Kumar Tripathi

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: Abstract Objectives of the current work were to investigate the role of photoperiod and melatonin in the alteration of immune responses in a reptilian species. Animals were kept on a regimen of short or long days. Blood was obtained and leucocytes were ... ...

Abstract	Abstract Objectives of the current work were to investigate the role of photoperiod and melatonin in the alteration of immune responses in a reptilian species. Animals were kept on a regimen of short or long days. Blood was obtained and leucocytes were isolated to study various innate immune responses. Lymphocytes were separated from blood by density gradient centrifugation and were used to study proliferation. Respiratory burst activity was measured through nitrobluetetrazolium reduction assay while nitric oxide production by leucocytes was assayed by nitrite assay. Lymphocytes were isolated and used to study proliferation with and without B and T cell mitogens. Photoperiodic manipulation acted differentially on leucocyte counts. Nitrite release was increased while superoxide production was decreased in cultures obtained from the snakes kept on the short day regimen. Significant enhancement of mitogen induced lymphocyte proliferation was observed in cultures from the animals kept in either long or short days compared to cultures from the animals kept in natural ambient day length. Use of in vitro melatonin showed that lymphocytes from the animals, kept in long days, were more reactive. Photoperiod induces changes in immune status which may permit adaptive functional responses in order to maintain seasonal energetic budgets of the animals. Physiological responses (like elevated immune status) are energetically expensive, therefore, animals have evolved a strategy to reduce immune functions at times when energy is invested in reproductive activities. Natrix piscator breeds from September to December and elevated pineal hormone in winter suppresses reproduction while immunity is stimulated.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The role of nitric oxide in brain disorders

Manish Kumar Tripathi / Maryam Kartawy / Haitham Amal

Redox Biology, Vol 34, Iss , Pp 101567- (2020)

Autism spectrum disorder and other psychiatric, neurological, and neurodegenerative disorders

2020

Abstract: Nitric oxide (NO) is a multifunctional signalling molecule and a neurotransmitter that plays an important role in physiological and pathophysiological processes. In physiological conditions, NO regulates cell survival, differentiation and proliferation ... ...

Abstract	Nitric oxide (NO) is a multifunctional signalling molecule and a neurotransmitter that plays an important role in physiological and pathophysiological processes. In physiological conditions, NO regulates cell survival, differentiation and proliferation of neurons. It also regulates synaptic activity, plasticity and vesicle trafficking. NO affects cellular signalling through protein S-nitrosylation, the NO-mediated posttranslational modification of cysteine thiols (SNO). SNO can affect protein activity, protein-protein interaction and protein localization. Numerous studies have shown that excessive NO and SNO can lead to nitrosative stress in the nervous system, contributing to neuropathology. In this review, we summarize the role of NO and SNO in the progression of neurodevelopmental, psychiatric and neurodegenerative disorders, with special attention to autism spectrum disorder (ASD). We provide mechanistic insights into the contribution of NO in diverse brain disorders. Finally, we suggest that pharmacological agents that can inhibit or augment the production of NO as well as new approaches to modulate the formation of SNO-proteins can serve as a promising approach for the treatment of diverse brain disorders.
Keywords	Nitric oxide ; S-nitrosylation ; Autism spectrum disorder ; Alzheimer's disease ; Psychiatry ; Neurodegeneration ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Seasonal variation and innate immune responses of spleen in fresh-water snake, Natrix piscator

Manish Kumar Tripathi / Ramesh Singh

Journal of Stress Physiology & Biochemistry, Vol 10, Iss 1, Pp 292-

2014 Volume 300

Abstract: Innate immunity provides first line defense in all animals against pathogens and parasites. There is seasonal variation in pathogen prevalence and disease because of the seasonal lifecycle of the parasite and due to annual variation in the infectivity of ...

Abstract	Innate immunity provides first line defense in all animals against pathogens and parasites. There is seasonal variation in pathogen prevalence and disease because of the seasonal lifecycle of the parasite and due to annual variation in the infectivity of pathogens. Organisms face seasonal stress by regulating their internal physiology, i.e. by secreting hormones. Melatonin and sex steroids contribute to the seasonal redistribution of immunological activity including winter-time up-regulation of some immune responses, and reproduction-related immunosuppression. Present study aims to understand seasonal variation in splenocyte innate immune response in the fresh-water snake, Natrix piscator. Reptiles represent the pivotal phylogenic group as they were the ancestor of both birds and mammals and they are the only ectothermic amniotes providing the key link between ectothermic anamniotic fishes and amphibians, and endothermic amniotic birds and mammals; a greater study of reptilian innate immune response will provide important insights into the evolutionary history of vertebrate immunity. Animals were mildly anaesthetized and the spleen was isolated aseptically. Spleen was used for calculating splenosomatic index, cellularity and macrophage phagocytosis. Spleen size has a trend to be high in autumn and winter months and low in spring and summer, though data were not significant. Spleen cellularity was recorded high in winter months and again in September; while it remained low during rest of the year. No definite pattern was observed in phagocytosis by splenic macrophages. The percent phagocytosis varied between 42 to 60 %, being highest in month of February. It is concluded that seasonal variation in splenocyte immune response provides a mechanism that suites best to the organism and which might coincide with the pathogen prevalence. Seasonal cycle of immune response is helpful in understanding the disease processes in animals and the direct implication of this study could be utilized for the endangered species living in captivity.
Keywords	Seasonal variation ; spleen ; immune response ; phagocytosis ; snake ; Ecology ; QH540-549.5 ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Ecology ; DOAJ:Earth and Environmental Sciences ; Biochemistry ; QD415-436
Subject code	590
Language	English
Publishing date	2014-03-01T00:00:00Z
Publisher	"Vikol publishing" ST Kolesnichenko V.V.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Differential suppressive effects of testosterone on immune function in fresh water snake, Natrix piscator

Manish Kumar Tripathi / Ramesh Singh

PLoS ONE, Vol 9, Iss 8, p e

an in vitro study.

2014 Volume 104431

Abstract: Reptiles represent the crucial phylogenetic group as they were the ancestors of both birds and mammals hence very important to study. The objectives of the present study were to investigate the potential roles of testosterone in the innate immune ... ...

Abstract	Reptiles represent the crucial phylogenetic group as they were the ancestors of both birds and mammals hence very important to study. The objectives of the present study were to investigate the potential roles of testosterone in the innate immune responses and splenic lymphocyte proliferation in fresh water snake, Natrix piscator. Animals were mildly anesthetized and spleens were taken out to study the splenic macrophage phagocytosis, super oxide production and nitrite release using in vitro testosterone. Splenic lymphocytes were isolated by density gradient centrifugation and were studied for mitogen induced proliferation in presence of in vitro testosterone. Testosterone suppressed the phagocytosis and nitrite release in a concentration dependent manner. Biphasic suppressive effect of testosterone was observed in superoxide production as judged by reduction of nitroblue tetrazolium salt where salt reduction was suppressed at lower and higher concentrations of testosterone. Mitogen induced splenic lymphocyte proliferation was also suppressed by testosterone. By suppressing immune responses, testosterone may, therefore, act as a physiological mechanism regulating the relative amount of energy invested into either reproductive effort or immunocompetence.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Photoperiodic stress on nitrite production by splenic macrophages in fresh-water snake Natrix piscator

Manish Kumar Tripathi / Ramesh Singh

Journal of Stress Physiology & Biochemistry

2012 Volume v. 8, Issue (2)

Abstract: Changes in day length enhance or suppress component of immune function in individuals of several species. The purpose of the present experiment was to study the role of photoperiodic manipulation on the nitric oxide production by splenic macrophages in ... ...

Abstract	Changes in day length enhance or suppress component of immune function in individuals of several species. The purpose of the present experiment was to study the role of photoperiodic manipulation on the nitric oxide production by splenic macrophages in the fresh-water snake, Natrix piscator. To study effect of photoperiod, animals were subjected to 24 hour continuous light and continuous dark for 30 days. Animals kept in natural day length served as control. At termination of experiments, animals were sacrificed, and spleen was excised. Macrophages were incubated for 24 hours and nitric oxide production was measured by measuring the nitrite concentration. Nitrite production was significantly decreased to the cultures obtained from the animals kept under continuous light. No change in nitrite concentration was found in animals kept under continuous dark, when compared to the animals kept under natural day length. The possible role of decreased melatonin synthesis in light is suggested to decrease the nitric oxide production.
Keywords	Nitric oxide ; Photoperiod ; snakes ; Macrophages ; Oxyde nitrique ; Photopériode ; Serpent ; Macrophage ; أوكسيد النيتريك ; ثعابين ; Óxido nítrico ; Fotoperiódo ; Culebra ; Macrofagos ; 一氧化氮 ; 光周期 ; 蛇眼镜 ; 巨噬细胞 ; http://aims.fao.org/aos/agrovoc/c_36996 ; http://aims.fao.org/aos/agrovoc/c_31879 ; http://aims.fao.org/aos/agrovoc/c_7122 ; http://aims.fao.org/aos/agrovoc/c_12316
Language	English
Document type	Article
ISSN	1997-0838
Database	AGRIS - International Information System for the Agricultural Sciences and Technology

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Article ; Online: Daily and seasonal rhythms in immune responses of splenocytes in the freshwater snake, Natrix piscator.

Manish Kumar Tripathi / Ramesh Singh / Atanu Kumar Pati

PLoS ONE, Vol 10, Iss 2, p e

2015 Volume 0116588

Abstract: Present study was designed to examine daily and seasonal variability in the innate immune responses of splenocytes in the fresh water snake, Natrix piscator. Animals were mildly anesthetized and spleen was aseptically isolated and processed for ... ...

Abstract	Present study was designed to examine daily and seasonal variability in the innate immune responses of splenocytes in the fresh water snake, Natrix piscator. Animals were mildly anesthetized and spleen was aseptically isolated and processed for macrophage phagocytosis, NBT reduction, nitrite production, splenocyte proliferation and serum lysozyme activity. Samples were collected at seven time points, viz., 0000, 0400, 0800, 1200, 1600, 2000 and 0000 h during three different seasons, namely summer, winter and spring. Cosinor analysis revealed that percent phagocytosis had a significant 24-h rhythm during summer and spring seasons. The peaks of rhythms in NBT reduction and nitrite release occurred in the morning hours at 10.88 h and 8.31 h, respectively, in winter. A significant 24-h rhythm was also observed in lysozyme concentration and splenocyte proliferation (both Basal and Concanavalin A stimulated) in all three seasons. A significant phase shift in splenocyte proliferation was obtained with a trend of delayed phase shift from winter to spring and from spring to summer. Of the nine variables, significant annual (seasonal) rhythms were detected in almost all variables, excluding phagocytic and splenosomatic indices. All rhythmic variables, except spleen cellularity, exhibited tightly synchronized peaks coinciding with the progressive and recrudescence phases of annual reproductive cycle. It is concluded that the snake synchronizes its daily and seasonal immune activity with the corresponding external time cues. The enhancement of immune function coinciding with one of its crucial reproductive phases might be helping it to cope with the seasonal stressors, including abundance of pathogens, which would otherwise jeopardize the successful reproduction and eventual survival of the species.
Keywords	Medicine ; R ; Science ; Q
Subject code	590
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interaction Analysis of MRP1 with Anticancer Drugs Used in Ovarian Cancer

Absarul Haque / Ghazanfar Ali Baig / Abdulelah Saleh Alshawli / Khalid Hussain Wali Sait / Bilal Bin Hafeez / Manish Kumar Tripathi / Badrah Saeed Alghamdi / Hani S. H. Mohammed Ali / Mahmood Rasool

Life, Vol 12, Iss 383, p

In Silico Approach

2022 Volume 383

Abstract: Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter ... ...

Abstract	Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.
Keywords	ovarian cancer ; multidrug resistance ; gemcitabine ; carboplatin ; multidrug resistance protein 1 ; Science ; Q
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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