Synapto-protective Effect of Lithium on HIV-1 Tat-induced Synapse Loss in Rat Hippocampal Cultures

Overview

Journal Anim Cells Syst (Seoul)

Specialty Biology

Date 2022 Mar 21

PMID 35308128

Authors

Namgue Hong

Jeong-Soo Park

Hee Jung Kim

Affiliations

Soon will be listed here.

Abstract

Human immunodeficiency virus type I (HIV-1) infection of the CNS produces synapse loss which correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). Lithium is mood stabilizer of unknown mechanism used to treat bipolar disorder and is known to exhibit neuroprotective properties. Here, we studied the effects of lithium on HIV-1 Tat-induced synapses between rat hippocampal neurons. The number of synapses was quantified to detect clusters of the scaffold protein postsynaptic density 95 (PSD95) which is clustered at glutamatergic synapses on cultured rat hippocampal neurons . Lithium protected synapses from HIV-1 Tat-induced synapse loss and subsequent neuronal death. This synaptic protection was prevented by both the activation of NMDA receptor leading to intracellular signaling and the regulatory pathway of lithium including inositol depletion and glycogen synthase kinase-3 (GSK-3). These results suggest that mood stabilizers might be effective drugs to treat neurodegenerative disorders including HAND.

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References

Joshi C, Stacy S, Sumien N, Ghorpade A, Borgmann K . Astrocyte HIV-1 Tat Differentially Modulates Behavior and Brain MMP/TIMP Balance During Short and Prolonged Induction in Transgenic Mice. Front Neurol. 2021; 11:593188. PMC: 7769877. DOI: 10.3389/fneur.2020.593188. View

Rubin L, Maki P . HIV, Depression, and Cognitive Impairment in the Era of Effective Antiretroviral Therapy. Curr HIV/AIDS Rep. 2019; 16(1):82-95. PMC: 6420829. DOI: 10.1007/s11904-019-00421-0. View

Maggirwar S, Tong N, Ramirez S, Gelbard H, Dewhurst S . HIV-1 Tat-mediated activation of glycogen synthase kinase-3beta contributes to Tat-mediated neurotoxicity. J Neurochem. 1999; 73(2):578-86. DOI: 10.1046/j.1471-4159.1999.0730578.x. View

Bonavia R, Bajetto A, Barbero S, Albini A, Noonan D, Schettini G . HIV-1 Tat causes apoptotic death and calcium homeostasis alterations in rat neurons. Biochem Biophys Res Commun. 2001; 288(2):301-8. DOI: 10.1006/bbrc.2001.5743. View

Lowthert L, Leffert J, Lin A, Umlauf S, Maloney K, Muralidharan A . Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation. Biol Mood Anxiety Disord. 2012; 2:15. PMC: 3448519. DOI: 10.1186/2045-5380-2-15. View

De Sarno P, Axtell R, Raman C, Roth K, Alessi D, Jope R . Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. J Immunol. 2008; 181(1):338-45. PMC: 2704026. DOI: 10.4049/jimmunol.181.1.338. View

Young W . Review of lithium effects on brain and blood. Cell Transplant. 2009; 18(9):951-75. DOI: 10.3727/096368909X471251. View

Qaswal A . Lithium Stabilizes the Mood of Bipolar Patients by Depolarizing the Neuronal Membrane Via Quantum Tunneling through the Sodium Channels. Clin Psychopharmacol Neurosci. 2020; 18(2):214-218. PMC: 7242109. DOI: 10.9758/cpn.2020.18.2.214. View

Tozzi V, Balestra P, Lorenzini P, Bellagamba R, Galgani S, Corpolongo A . Prevalence and risk factors for human immunodeficiency virus-associated neurocognitive impairment, 1996 to 2002: results from an urban observational cohort. J Neurovirol. 2005; 11(3):265-73. DOI: 10.1080/13550280590952790. View

10.

DellOsso L, Del Grande C, Gesi C, Carmassi C, Musetti L . A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salts. Neuropsychiatr Dis Treat. 2016; 12:1687-703. PMC: 4946830. DOI: 10.2147/NDT.S106479. View

11.

Nassar A, Azab A . Effects of lithium on inflammation. ACS Chem Neurosci. 2014; 5(6):451-8. PMC: 4063502. DOI: 10.1021/cn500038f. View

12.

Kim H, Thayer S . Lithium increases synapse formation between hippocampal neurons by depleting phosphoinositides. Mol Pharmacol. 2009; 75(5):1021-30. PMC: 2672813. DOI: 10.1124/mol.108.052357. View

13.

Angelino A, Treisman G . Management of psychiatric disorders in patients infected with human immunodeficiency virus. Clin Infect Dis. 2001; 33(6):847-56. DOI: 10.1086/322679. View

14.

Manji H, Moore G, Chen G . Lithium at 50: have the neuroprotective effects of this unique cation been overlooked?. Biol Psychiatry. 1999; 46(7):929-40. DOI: 10.1016/s0006-3223(99)00165-1. View

15.

Inestrosa N, Varela-Nallar L . Wnt signaling in the nervous system and in Alzheimer's disease. J Mol Cell Biol. 2014; 6(1):64-74. DOI: 10.1093/jmcb/mjt051. View

16.

Everall I, Bell C, Mallory M, Langford D, Adame A, Rockestein E . Lithium ameliorates HIV-gp120-mediated neurotoxicity. Mol Cell Neurosci. 2002; 21(3):493-501. DOI: 10.1006/mcne.2002.1196. View

17.

Berridge M . The Albert Lasker Medical Awards. Inositol trisphosphate, calcium, lithium, and cell signaling. JAMA. 1989; 262(13):1834-41. View

18.

Letendre S, Woods S, Ellis R, Atkinson J, Masliah E, Van Den Brande G . Lithium improves HIV-associated neurocognitive impairment. AIDS. 2006; 20(14):1885-8. DOI: 10.1097/01.aids.0000244208.49123.1b. View

19.

Kim B, Liu Y, Ruan Y, Xu Z, Schantz L, He J . Neuropathologies in transgenic mice expressing human immunodeficiency virus type 1 Tat protein under the regulation of the astrocyte-specific glial fibrillary acidic protein promoter and doxycycline. Am J Pathol. 2003; 162(5):1693-707. PMC: 1851199. DOI: 10.1016/S0002-9440(10)64304-0. View

20.

Sa M, Madeira M, Ruela C, Volk B, Mota-Miranda A, Paula-Barbosa M . Dendritic changes in the hippocampal formation of AIDS patients: a quantitative Golgi study. Acta Neuropathol. 2003; 107(2):97-110. DOI: 10.1007/s00401-003-0781-3. View