Kiran Chaudhari

University of North Texas

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Ali Winters

University of North Texas

Ran Liu

West China Hospital of Sichuan University

Nathalie Sumien

University of North Texas Health Science Center

Shao‐Hua Yang

North China Institute of Aerospace Engineering

Linshu Wang

University of North Texas

Jude Prah

University of North Texas

Yuanhong Sun

University of Oklahoma

R. S. R. Murthy

Technology Information, Forecasting and Assessment Council

Michael J. Forster

University of North Texas

Philip H. Vann

University of North Texas

Cooperative Institutions

University of North Texas

University of North Texas Health Science Center

Yale University

Maharaja Sayajirao University of Baroda

Government Medical College

Capital Medical University

Technology Information, Forecasting and Assessment Council

The University of Texas Southwestern Medical Center

Wuhan University

Sun Yat-sen University

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AMPKα2 and Neuronal Structure: Implications for Metformin (P2-3.004)

Neurology (2022)

Jonas Kruse Kiran Chaudhari Linshu Wang Ali Winters Ran Liu

To determine whether AMPK plays a critical role in structural formation and maintenance of neurons, axons, and dendritic branches, which ultimately leads to synapse formation and signal transduction.

10.1212/wnl.98.18_supplement.1210

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Recurrent Transient Ischemic Attack Induces Neural Cytoskeleton Modification and Gliosis in an Experimental Model

Translational Stroke Research (2022)

Linshu Wang Kiran Chaudhari Ali Winters Yuanhong Sun Raymond Berry

Gliosis

Astrogliosis

10.1007/s12975-022-01068-7

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Citations (1)

Exercise training and antioxidant supplementation independently improve cognitive function in adult male and female GFAP-APOE mice

Journal of sport and health science/Journal of Sport and Health Science (2014)

Kiran Chaudhari Jessica M. Wong Philip H. Vann Nathalie Sumien

The purpose of this study was to determine if antioxidant supplementation, moderate exercise, and the combination of both treatments could ameliorate cognitive performance in adult mice and whether the apolipoprotein E (APOE) genotype as well as sex could influence the functional outcomes of the treatments. For a period of 16 weeks, separate groups of male and female mice expressing either the human APOE3 or APOE4 isoforms were fed either a control diet (NIH-31) or the control diet supplemented with vitamins E and C (1.12 IU/g diet α-tocopheryl acetate and 1.65 mg/g ascorbic acid). The mice were further separated into a sedentary group or a group that followed a daily exercise regimen. After 8 weeks on the treatments, the mice were administered a battery of functional tests including tests to measure cognitive and affective function. There was no effect of genotype or treatment on the learning performance in the Morris water maze. In the discriminated avoidance task, APOE4 mice performed better in learning the discrimination component of the task. Overall, exercise improved performance of APOE4 and APOE3 mice on various aspects of the active avoidance task. Antioxidant supplementation improved performance only in the APOE4 mice. On the test for anxiety, APOE4 mice spent more time in the open arms and supplementation with antioxidant reversed that effect. Exercise was the most effective treatment at improving cognitive function in both genotypes and sex, while antioxidants seemed to be effective only in the APOE4. In young adult mice only non-spatial learning and memory were improved. The combination of the two treatments did not yield further improvement in cognition, and there was no antagonistic action of the antioxidant supplementation on the beneficial effects of exercise.

Apolipoprotein E

Water maze

10.1016/j.jshs.2014.04.004

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Citations (16)

Metabolic Heterogeneity of Cerebral Cortical and Cerebellar Astrocytes

Life (2023)

Yuanhong Sun Ali Winters Linshu Wang Kiran Chaudhari Raymond Berry

Astrocytes play critical roles in regulating neuronal synaptogenesis, maintaining blood–brain barrier integrity, and recycling neurotransmitters. Increasing numbers of studies have suggested astrocyte heterogeneity in morphology, gene profile, and function. However, metabolic phenotype of astrocytes in different brain regions have not been explored. In this paper, we investigated the metabolic signature of cortical and cerebellar astrocytes using primary astrocyte cultures. We observed that cortical astrocytes were larger than cerebellar astrocytes, whereas cerebellar astrocytes had more and longer processes than cortical astrocytes. Using a Seahorse extracellular flux analyzer, we demonstrated that cortical astrocytes had higher mitochondrial respiration and glycolysis than cerebellar astrocytes. Cerebellar astrocytes have lower spare capacity of mitochondrial respiration and glycolysis as compared with cortical astrocytes. Consistently, cortical astrocytes have higher mitochondrial oxidation and glycolysis-derived ATP content than cerebellar astrocytes. In addition, cerebellar astrocytes have a fuel preference for glutamine and fatty acid, whereas cortical astrocytes were more dependent on glucose to meet energy demands. Our study indicated that cortical and cerebellar astrocytes display distinct metabolic phenotypes. Future studies on astrocyte metabolic heterogeneity and brain function in aging and neurodegeneration may lead to better understanding of the role of astrocyte in brain aging and neurodegenerative disorders.

10.3390/life13010184

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Laminin receptor-targeted etoposide loaded polymeric micelles: a novel approach for the effective treatment of tumor metastasis

Journal of drug targeting (2011)

Mukesh Ukawala Kiran Chaudhari Tushar Rajyaguru Arehalli S. Manjappa R. S. R. Murthy

Background: Tumor-targeted delivery is a desirable approach to improve therapeutic outcome of anticancer drug due to enhanced efficacy and reduced toxicity.Purpose: The present study was aimed to target laminin receptor over-expressed tumor cells using YIGSR (Tyr-Ile-Gly-Ser-Arg) conjugated etoposide loaded micelles in the treatment of metastasis.Methods: YIGSR conjugated micelles prepared using synthesized carboxyl and methoxy terminated poly(ethylene glycol)-b-poly(ϵ-caprolactone) block copolymers were evaluated for it efficacy against highly metastatic B16F10 cell lines conducting cytotoxicity, colony formation, cell migration, cellular uptake and flow cytometry studies. The in-vivo antimetastatic effect of micelles was evaluated using experimental metastatic model on C57BL/6 mice.Results: YIGSR conjugated micelles of particle size 45.2 ± 3.77 nm and zeta potential of−5.7 ± 1.3 mV demonstrated enhanced cytotoxicity and cellular uptake with significant reduction in colony formation and cell migration activities compared to non-conjugated micelles. Furthermore, a markedly inhibition in lung colony formation was observed with these micelles.Discussion: An enhanced cellular internalization of YIGSR conjugated micelles due to laminin receptor based endocytosis resulted in to higher cytotoxicity as well as antimetastatic effect against highly metastatic B16F10 cells.Conclusion: These studies indicate that YIGSR conjugated nanocarrier can be a promising approach in the treatment of tumor metastasis.

Internalization

Nanocarriers

10.3109/1061186x.2011.610799

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Citations (18)

Direct Conversion of Olefins into α-Bromo Ketones Using O-Iodoxybenzoic Acid and Tetraethylammonium Bromide

Synlett (2010)

Krishnacharya G. Akamanchi Swapnil Deshmukh Kiran Chaudhari

Corrected by: Direct Conversion of Olefins into α-Bromo Ketones Using O-Iodoxybenzoic Acid and Tetraethylammonium BromideSynlett 2011; 2011(01): e1-e1DOI: 10.1055/s-0030-1259279

Tetraethylammonium

10.1055/s-0030-1259090

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Metformin Alters Locomotor and Cognitive Function and Brain Metabolism in Normoglycemic Mice

Aging and Disease (2019)

Wenjun Li Kiran Chaudhari Ritu A. Shetty Ali Winters Xiaofei Gao

Metformin is currently the most effective treatment for type-2 diabetes. The beneficial actions of metformin have been found even beyond diabetes management and it has been considered as one of the most promising drugs that could potentially slow down aging. Surprisingly, the effect of metformin on brain function and metabolism has been less explored given that brain almost exclusively uses glucose as substrate for energy metabolism. We determined the effect of metformin on locomotor and cognitive function in normoglycemic mice. Metformin enhanced locomotor and balance performance, while induced anxiolytic effect and impaired cognitive function upon chronic treatment. We conducted in vitro assays and metabolomics analysis in mice to evaluate metformin's action on the brain metabolism. Metformin decreased ATP level and activated AMPK pathway in mouse hippocampus. Metformin inhibited oxidative phosphorylation and elevated glycolysis by inhibiting mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) in vitro at therapeutic doses. In summary, our study demonstrated that chronic metformin treatment affects brain bioenergetics with compound effects on locomotor and cognitive brain function in non-diabetic mice.

Brain Function

10.14336/ad.2019.0120

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Citations (44)

Characterizing region-specific glucose metabolic profile of the rodent brain using Seahorse XFe96 analyzer

Journal of Cerebral Blood Flow & Metabolism (2022)

Linshu Wang Kiran Chaudhari Ali Winters Yuanhong Sun Ran Liu

The brain is highly complex with diverse structural characteristics in accordance with specific functions. Accordingly, differences in regional function, cellular compositions, and active metabolic pathways may link to differences in glucose metabolism at different brain regions. In the current study, we optimized an acute biopsy punching method and characterized region-specific glucose metabolism of rat and mouse brain by a Seahorse XFe96 analyzer. We demonstrated that 0.5 mm diameter tissue punches from 180-µm thick brain sections allow metabolic measurements of anatomically defined brain structures using Seahorse XFe96 analyzer. Our result indicated that the cerebellum displays a more quiescent phenotype of glucose metabolism than cerebral cortex, basal ganglia, and hippocampus. In addition, the cerebellum has higher AMPK activation than other brain regions evidenced by the expression of pAMPK, upstream pLKB1, and downstream pACC. Furthermore, rodent brain has relatively low mitochondrial oxidative phosphorylation efficiency with up to 30% of respiration linked to proton leak. In summary, our study discovered region-specific glucose metabolic profile and relative high proton leak coupled respiration in the brain. Our study warrants future research on spatial mapping of the brain glucose metabolism in physiological and pathological conditions and exploring the mechanisms and significance of mitochondrial uncoupling in the brain.

Carbohydrate Metabolism

10.1177/0271678x221077341

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Citations (6)

Novel and Facile Transformation of N,N-Disubstituted Glycylamides into Corresponding Cyanamides by Using Pentavalent Iodine Reagents in Combination with Tetraethylammonium Bromide

Synlett (2007)

Krishnacharya G. Akamanchi Kiran Chaudhari Ulhas S. Mahajan Dinesh S. Bhalerao

Novel and facile transformation of N,N-disubstituted glycylamides into corresponding cyanamides using pentavalent iodine reagents and tetraethylammonium bromide is discussed. The advantages of this system are use of non toxic reagents, shorter reaction times and moderate to good yields.

Tetraethylammonium

10.1055/s-2007-991093

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Citations (12)

Direct Conversion of Olefins into α-Bromo Ketones Using O-Iodoxybenzoic Acid and Tetraethylammonium Bromide

Synlett (2010)

Krishnacharya G. Akamanchi Swapnil Deshmukh Kiran Chaudhari

Correction to: Direct Conversion of Olefins into α-Bromo Ketones Using O-Iodoxybenzoic Acid and Tetraethylammonium BromideSynlett 2011; 2011(01): 81-83DOI: 10.1055/s-0030-1259090

Tetraethylammonium

10.1055/s-0030-1259279

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Citations (0)