Vesna Tesic, PhD (P.I.)

RESEARCH

Alzheimer's disease is a neurodegenerative disease with progressive impairment of behavioral and cognitive functions including memory, comprehension, language, attention, reasoning, and judgment. It is the sixth leading cause of death in the United States. An estimated 6.7 million Americans age 65 and older are living with Alzheimer's in 2023. There is no cure for Alzheimer's disease, although there are treatments available that may improve some symptoms. The research goal of our lab is understanding key pathways involved in cognitive deterioration with aging and neurodegenerative diseases, with particular focus on Alzheimer’s disease. We aim to understand and identify the molecular events that are underlying cognitive deterioration by identifying new pathways and degenerative changes in synaptic plasticity, mitochondrial function, and neurovascular coupling in the brain. We are also investigating the involvement of stress-related pathways in aging- and neurodegenerative diseases-induced pathology in the brain. We are establishing the novel use of non-neurotoxic neurosteroid compounds that can modulate the progression of learning and memory impairment.

Lab’s research efforts are pointed towards using the modulation of the mechanisms underlying detrimental processes leading to the cognitive impairment with the goal to test novel therapeutic approaches and prevent and/or ameliorate progression of neurodegeneration.

Ganaxolone (GNX) treatment prevented neurovascular coupling deficits in aged female 3xTgAD mice. (A) Neurovascular coupling was evaluated based on vascular tonicity changes in response to whisker stimulation (30 sec, 4 Hz) via two-photon laser scanning microscopy. (B) Vessel diameters were measured before/after whisker stimulation in young and aged 3xTgAD mice +/- GNX. Young mice had a vasodilatory response to whisker stimulation contrary to their aged counterparts. Microvessel diameters were increased in aged mice after GNX treatment to suggest recovery of neurovascular coupling. (C) FITC-dextran was injected IV for visualization of cortical microvessels (Z=100 µm depth). (D) GNX treated aged 3xTgAD mice had higher red blood cells (RBC) velocity, in accordance with increased blood vessel diameter. *p<0.05 aged 3xTgAD Control vs. all other groups determined via one-way ANOVA with Tukey's post-hoc analysis (B) or unpaired t-test (D).

Ganaxolone (GNX) treatment increased mitochondrial reserve capacity in aged 3xTgAD female mice. (A) Changes in mitochondrial respiration were observed by injection of 20 μg/ml oligomycin, 1 mM pyruvate and 80 μM carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), and 20 μM antimycin. (B) Mitochondrial Reserve Capacity was increased in GNX treated aged 3xTgAD mice to suggest the increased capability of mitochondria to respond to stressors such as ROS/RNS. Oxygen consumption rate (OCR) was measured in the hippocampal slices (200 μm) of control or GNX treated aged 3xTgAD animals via Seahorse XFe24 analyzer. *p<0.05 vs. aged control 3xTgAD animals, evaluated by unpaired t-test.

Selected Publications

1. Marquez-Ortiz RA¹, Tesic V¹, Hernandez DR, Akhter B, Aich N, Boudreaux PM, Clemons GA, Wu CY, Lin HW, Rodgers KM. Neuroimmune Support of Neuronal Regeneration and Neuroplasticity following Cerebral Ischemia in Juvenile Mice. Brain Sci. 2023 Sep 17;13(9):1337. doi: 10.3390/brainsci13091337. PMID: 37759938,  ¹ equal contribution
2. Acosta CH, Clemons GA, Citadin CT, Carr WC, Udo MSB, Tesic V, Sanicola HW, Freelin AH, Toms JB, Jordan JD, Guthikonda B, Rodgers KM, Wu CY, Lee RH, Lin HW. PRMT7 can prevent neurovascular uncoupling, blood-brain barrier permeability, and mitochondrial dysfunction in repetitive and mild traumatic brain injury. Exp Neurol. 2023 Aug;366:114445. doi: 10.1016/j.expneurol.2023.114445. Epub 2023 May 15. PMID: 37196697.
3. Fine-Raquet B, Manzella FM, Joksimovic SM, Dietz RM, Orfila JE, Sampath D, Tesic V, Atluri N, Covey DF, Raol YH, Jevtovic-Todorovic V, Herson PS, Todorovic SM. Neonatal exposure to a neuroactive steroid alters low-frequency oscillations in the subiculum. Exp Biol Med (Maywood). 2023 Apr;248(7):578-587. doi: 10.1177/15353702231177009. Epub 2023 Jun 13. PMID: 37309730.
4. Acosta CH, Clemons GA, Citadin CT, Carr WC, Udo MSB, Tesic V, Sanicola HW, Freelin AH, Toms JB, Jordan JD, Guthikonda B, Wu CY, Lee RH, Lin HW. (2023) A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury. Neurochem Int. PMID: 37030326.
5. Joksimovic SM, Ghodsi SM, Heinsbroek JA, Orfila JE, Busquet N, Tesic V, Valdez R, Fine-Raquet B, Jevtovic-Todorovic V, Raol YH, Herson PS, Todorovic SM. (2023) CaV3.1 T-type calcium channels are important for spatial memory processing in the dorsal subiculum. Neuropharmacology. PMID: 36586474; PMCID: PMC9898223.
6. Ciric J, Tesic V, Milovanovic N, Jovanovic Macura I, Ivkovic S, Kanazir S, Perovic M. Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging. Brain Sci. 2022 Sep 26;12(10). PMID: 36291231; PMCID: PMC9599456.
7. Clemons GA, Silva ACE, Acosta CH, Udo MSB, Tesic V, Rodgers KM, Wu CY, Citadin CT, Lee RH, Neumann JT, Allani S, Prentice H, Zhang Q, Lin HW. (2022) Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease. J Cell Physiol. PMID: 36036549.
8. Tesic V, Ciric J, Jovanovic Macura I, Zogovic N, Milanovic D, Kanazir S, Perovic M. (2021) Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction. Nutrients, 13 (12), 4526.  PMID: 34960078; PMCID: PMC8703853.
9. Marquez-Ortiz RA, Contreras-Zarate MJ, Tesic V, Alvarez-Eraso KLF, Kwak G, Littrell Z, Costello JC, Sreekanth V, Ormond DR, Karam SD, Kabos P, Cittelly DM. (2021) IL13Rα2 Promotes Proliferation and Outgrowth of Breast Cancer Brain Metastases. Clin Cancer Res. 15;27(22):6209-6221. PMID: 34544797; PMCID: PMC8595859.
10. Manzella FM, Joksimovic SM, Orfila JE, Fine BR, Dietz RM, Sampath D, Fiedler HK, Tesic V, Atluri N, Raol YH, Jevtovic-Todorovic V, Herson PS, Todorovic SM. (2020) Neonatal Ketamine Alters High-Frequency Oscillations and Synaptic Plasticity in the Subiculum But Does not Affect Sleep Macrostructure in Adolescent Rats. Front Syst Neurosci. 26; 14:26. PMID: 32528257; PMCID: PMC7264261. 
11. Tesic V, Joksimovic SM, Quillinan N, Krishnan K, Covey DF, Todorovic SM, Jevtovic-Todorovic V. (2020) Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABAA currents, but are not neurotoxic to the developing rat brain. British Journal of Anaesthesia, 124(5):603-613. PMID: 32151384; PMCID: PMC7222221.
12. Lazic D¹, Tesic V¹, Jovanovic M, Brkic M, Milanovic D, Zlokovic BV, Kanazir S, Perovic M. (2020) Every-other day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease.  Neurobiol Dis. 136:104745. PMID: 31931140.  ¹ equal contribution
13. Cabrera OH, Tesic V, Tat QL, Chastain S, Quillinan N, Jevtovic-Todorovic V. (2020) Sevoflurane-Induced Dysregulation of Cation-Chloride Cotransporters NKCC1 and KCC2 in Neonatal Mouse Brain. Mol Neurobiol 57(1):1–10. PMID: 31493242; PMCID: PMC6980440.
14. Chastain-Potts SE, Tesic V, Tat QL, Cabrera OH, Quillinan N, Jevtovic-Todorovic V. (2020) Sevoflurane Exposure Results in Sex-Specific Transgenerational Upregulation of Target IEGs in the Subiculum. Mol Neurobiol. 57(1):11-22. PMID: 31512116; PMCID: PMC6980510.
15. Woodward TJ, Tesic V, Stamenic TT, Jevtovic-Todorovic V, Todorovic SM. (2019) Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for a-Lipoic Acid. Front Pharmacol.; 10:1402.  PMID: 31849661; PMCID: PMC6889856.
16. Joksimovic SM, Izumi Y, Joksimovic SL, Tesic V, Krishnan K, Asnake B, Jevtovic-Todorovic V, Covey DF, Zorumski CF, Todorovic SM. (2019) Novel neurosteroid hypnotic blocks T-type calcium channel-dependent rebound burst firing and suppresses long-term potentiation in the rat subiculum, British Journal of Anaesthesia, 122;5; 643- 651. PMID: 30916017; PMCID: PMC6549045.
17. Joksimovic SL, Joksimovic SM, Tesic V, García-Caballero A, Feseha S, Zamponi GW, Jevtovic-Todorovic V, Todorovic SM. (2018) Selective inhibition of CaV3.2 channels reverses hyperexcitability of peripheral nociceptors and alleviates postsurgical pain. Sci Signal. 28;11(545). PMID: 30154101; PMCID: PMC6193449.
18. Tracy ME, Tesic V, Timic Stamenic T, Joksimovic SM, Busquet N, Jevtovic-Todorovic V, Todorovic SM. (2018) CaV3.1 isoform of T-type calcium channels supports excitability of rat and mouse ventral tegmental area neurons. Neuropharmacology, Vol. 135, 343-354; PMID: 29578032; PMCID: PMC5975125.
19. Joksimovic SM, Eggan P, Izumi Y, Joksimovic SL, Tesic V, Dietz RM, Orfila JE, DiGruccio MR, Herson PS, Jevtovic-Todorovic V, Zorumski CF, Todorovic SM. (2017) The role of T-type calcium channels in the subiculum:  to burst or not to burst? J Physiol.; 595(19):6327-6348. PMID: 28744923; PMCID: PMC5621493.  
20. Tesic V, Perovic M, Zaletel I, Jovanovic M, Puskas N, Ruzdijic S, Kanazir S. (2017) A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats. Exp Gerontol.; 98:62- 69. PMID: 28801169. 
21. Milanovic D, Pesic V, Loncarevic-Vasiljkovic N, Avramovic V, Tesic V, Jevtovic-Todorovic V, Kanazir S, Ruzdijic S. (2017) Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats. Neurotox Res.; 32(2):247-263. PMID: 28435999. 
22. Milosev MZ, Jakovljević K, Joksovic MD, Stanojkovic T, Matic IZ, Perovic M, Tesic V, Kanazir S, Mladenovic M, Rodic MV, Leovac VM, Trifunovic S, Markovic V. (2017) Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies. Chem Biol Drug Des. 89(6):943-952. PMID: 27933733.
23. Loncarevic-Vasiljkovic N, Milanovic D, Pesic V, Tesic V, Brkic M, Lazic D, Avramovic V, Kanazir S. (2016) Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury. Neurochem Int. 96:69-76. PMID: 26939764.
24. Tesic V, Perovic M, Lazic D, Kojic S, Smiljanic K, Rakic L, Ruzdijic S, Kanazir S. (2015) Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat. Journal of Steroid Biochemistry and Molecular Biology, 149:43-52. PMID: 25616002.
25. Markovic V, Debeljak N, Stanojkovic T, Kolundzija B, Sladic D, Vujcic M, Janovic B, Tanic N, Perovic M, Tesic V, Antic J, Joksovic MD, (2015) Anthraquinone-chalcone hybrids: Synthesis, preliminary antiproliferative evaluation and DNA-interaction studies. European Journal of Medicinal Chemistry, 89:401-10. PMID: 25462255.  
26. Pesic V, Milanovic D, Popic J, Smiljanic K, Tesic V, Kanazir S, Jevtovic-Todorovic V, Ruzdijic S. (2015) Neonatal propofol anesthesia modifies activity-dependent processes and induces transient hyperlocomotor response to d-amphetamine during adolescence in rats. Int J DevNeurosci, 47:266-277. PMID: 26492981.  
27. Mladenovic Djordjevic A, Perovic M, Smiljanic K, Todorovic S, Tesic V, Ruzdijic S, Kanazir S. (2014) The effects of dietary restriction and aging on amyloid precursor protein and presenilin-1 mRNA and protein expression in rat brain. Neuroreport, 25(6):398-403. PMID: 24346258.
28. Smiljanic K, Vanmierlo T, Mladenovic Djordjevic A, Perovic M, Loncarevic-Vasiljkovic N, Tesic V, Rakic L, Ruzdijic S, Lutjohann D, Kanazir S. (2013) Aging induces tissue-specific changes in cholesterol metabolism in rat brain and liver. Lipids, 48(11):1069-77. PMID: 24057446.
29. Perovic M, Tesic V, Mladenovic Djordjevic A, Smiljanic K, Loncarevic-Vasiljkovic N, Ruzdijic S, Kanazir S. (2013) BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. AGE, 35(6):2057-70. PMID: 23255148.
30. Mladenovic Djordjevic A, Perovic M, Tesic V, Tanic N, Rakic L, Ruzdijic S, Kanazir S. (2010) Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat.  Neurochem. Int., 56:250–255. PMID: 19878701.

Post-doctoral Fellows and Graduate Students