DPP-4 inhibitor reduces striatal microglial deramification after sensorimotor cortex injury induced by external force impact.
Animals
Brain Injuries, Traumatic
/ drug therapy
Chemokine CCL2
/ metabolism
Dipeptidyl-Peptidase IV Inhibitors
/ pharmacology
Disease Models, Animal
Galectin 3
/ metabolism
Glucagon-Like Peptide 1
/ blood
Interleukin-10
Male
Mice
Mice, Inbred C57BL
Microglia
/ drug effects
Neuroprotective Agents
/ pharmacology
Sensorimotor Cortex
/ drug effects
Sitagliptin Phosphate
/ pharmacology
Vildagliptin
/ pharmacology
Visual Cortex
/ drug effects
controlled cortical impact
dorsolateral striatum
microglial ramification
sitagliptin
traumatic brain injury
vildagliptin
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
11
11
2019
revised:
08
03
2020
accepted:
17
03
2020
pubmed:
5
4
2020
medline:
28
1
2021
entrez:
5
4
2020
Statut:
ppublish
Résumé
Dipeptidyl peptidase-4 inhibitors (or gliptins), a class of antidiabetic drugs, have recently been shown to have protective actions in the central nervous system. Their cellular and molecular mechanisms responsible for these effects are largely unknown. In the present study, two structurally different gliptins, sitagliptin and vildagliptin, were examined for their therapeutic actions in a controlled cortical impact (CCI) model of moderate traumatic brain injury (TBI) in mice. Early post-CCI treatment with sitagliptin, but not vildagliptin, significantly reduced body asymmetry, locomotor hyperactivity, and brain lesion volume. Sitagliptin attenuated post-CCI microglial deramification in the ipsilateral dorsolateral (DL) striatum, while vildagliptin had no effect. Sitagliptin also reduced striatal expression of galectin-3 and monocyte chemoattractant protein 1(MCP-1), and increased the cortical and striatal levels of the anti-inflammatory cytokine IL-10 on the ipsilateral side. These data support a differential protective effect of sitagliptin against TBI, possibly mediated by an anti-inflammatory effect in striatum to preserve connective network. Both sitagliptin and vildagliptin produced similar increases of active glucagon-like peptide-1 (GLP-1) in blood and brain. Increasing active GLP-1 may not be the sole molecular mechanisms for the neurotherapeutic effect of sitagliptin in TBI.
Identifiants
pubmed: 32246809
doi: 10.1096/fj.201902818R
doi:
Substances chimiques
Ccl2 protein, mouse
0
Chemokine CCL2
0
Dipeptidyl-Peptidase IV Inhibitors
0
Galectin 3
0
IL10 protein, mouse
0
Lgals3 protein, mouse
0
Neuroprotective Agents
0
Interleukin-10
130068-27-8
Glucagon-Like Peptide 1
89750-14-1
Vildagliptin
I6B4B2U96P
Sitagliptin Phosphate
TS63EW8X6F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6950-6964Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
Références
Vanderploeg RD, Curtiss G, Luis CA, Salazar AM. Long-term morbidities following self-reported mild traumatic brain injury. J Clin Exp Neuropsychol. 2007;29:585-598.
Corrigan JD, Selassie AW, Orman JA. The epidemiology of traumatic brain injury. J Head Trauma Rehabil. 2010;25:72-80.
Raghupathi R. Cell death mechanisms following traumatic brain injury. Brain Pathol. 2004;14:215-222.
Russell S. Incretin-based therapies for type 2 diabetes mellitus: a review of direct comparisons of efficacy, safety and patient satisfaction. Int J Clin Pharm. 2013;35:159-172.
Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993;214:829-835.
Ahren B, Hughes TE. Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice. Endocrinology. 2005;146:2055-2059.
Gupta V, Kalra S. Choosing a gliptin. Indian J Endocrinol Metab. 2011;15:298-308.
Berger JP, SinhaRoy R, Pocai A, et al. A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice. Endocrinol Diabetes Metab. 2018;1:e00002.
Chen DY, Wang SH, Mao CT, et al. Sitagliptin after ischemic stroke in type 2 diabetic patients: a nationwide cohort study. Medicine. 2015;94:e1128.
Tziomalos K, Bouziana SD, Spanou M, et al. Prior treatment with dipeptidyl peptidase 4 inhibitors is associated with better functional outcome and lower in-hospital mortality in patients with type 2 diabetes mellitus admitted with acute ischaemic stroke. Diab Vasc Dis Res. 2015;12:463-466.
Isik AT, Soysal P, Yay A, Usarel C. The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer's disease. Diabetes Res Clin Pract. 2017;123:192-198.
Pintana H, Apaijai N, Chattipakorn N, Chattipakorn SC. DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats. J Endocrinol. 2013;218:1-11.
Pipatpiboon N, Pintana H, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. DPP4-inhibitor improves neuronal insulin receptor function, brain mitochondrial function and cognitive function in rats with insulin resistance induced by high-fat diet consumption. Eur J Neurosci. 2013;37:839-849.
Darsalia V, Ortsater H, Olverling A, et al. The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride. Diabetes. 2013;62:1289-1296.
Kosaraju J, Gali CC, Khatwal RB, et al. Saxagliptin: a dipeptidyl peptidase-4 inhibitor ameliorates streptozotocin induced Alzheimer's disease. Neuropharmacology. 2013;72:291-300.
Kosaraju J, Murthy V, Khatwal RB, et al. Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease. J Pharm Pharmacol. 2013;65:1773-1784.
Abdelsalam RM, Safar MM. Neuroprotective effects of vildagliptin in rat rotenone Parkinson's disease model: role of RAGE-NFkappaB and Nrf2-antioxidant signaling pathways. J Neurochem. 2015;133:700-707.
Tsai TH, Sun CK, Su CH, et al. Sitagliptin attenuated brain damage and cognitive impairment in mice with chronic cerebral hypo-perfusion through suppressing oxidative stress and inflammatory reaction. J Hypertens. 2015;33:1001-1013.
DellaValle B, Brix GS, Brock B, Gejl M, Rungby J, Larsen A. Oral administration of sitagliptin activates CREB and is neuroprotective in murine model of brain trauma. Front Pharmacol. 2016;7:450.
Hall ED, Sullivan PG, Gibson TR, Pavel KM, Thompson BM, Scheff SW. Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: more than a focal brain injury. J Neurotrauma. 2005;22:252-265.
Borlongan CV, Sanberg PR. Elevated body swing test: a new behavioral parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism. J Neurosci. 1995;15:5372-5378.
Ingberg E, Gudjonsdottir J, Theodorsson E, Theodorsson A, Strom JO. Elevated body swing test after focal cerebral ischemia in rodents: methodological considerations. BMC Neurosci. 2015;16:50.
Morrison H, Young K, Qureshi M, Rowe RK, Lifshitz J. Quantitative microglia analyses reveal diverse morphologic responses in the rat cortex after diffuse brain injury. Sci Rep. 2017;7:13211.
Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676-682.
Young K, Morrison H. Quantifying microglia morphology from photomicrographs of immunohistochemistry prepared tissue using ImageJ. J Vis Exp. 2018:e57648. https://doi.org/10.3791/57648.
Haage V, Semtner M, Vidal RO, et al. Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma. Acta Neuropathol Commun. 2019;7:20.
Jain S, Sharma B. Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia. Physiol Behav. 2015;152:182-193.
Gault VA, Lennox R, Flatt PR. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, improves recognition memory, oxidative stress and hippocampal neurogenesis and upregulates key genes involved in cognitive decline. Diabetes Obes Metab. 2015;17:403-413.
Chen S, Yu SJ, Li Y, et al. Post-treatment with PT302, a long-acting Exendin-4 sustained release formulation, reduces dopaminergic neurodegeneration in a 6-Hydroxydopamine rat model of Parkinson's disease. Sci Rep. 2018;8:10722.
Li Y, Perry T, Kindy MS, et al. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci U S A. 2009;106:1285-1290.
Ewen T, Qiuting L, Chaogang T, et al. Neuroprotective effect of atorvastatin involves suppression of TNF-alpha and upregulation of IL-10 in a rat model of intracerebral hemorrhage. Cell Biochem Biophys. 2013;66:337-346.
Atkins S, Loescher AR, Boissonade FM, et al. Interleukin-10 reduces scarring and enhances regeneration at a site of sciatic nerve repair. J Peripher Nerv Syst. 2007;12:269-276.
Manley NC, Bertrand AA, Kinney KS, Hing TC, Sapolsky RM. Characterization of monocyte chemoattractant protein-1 expression following a kainate model of status epilepticus. Brain Res. 2007;1182:138-143.
Stamatovic SM, Shakui P, Keep RF, et al. Monocyte chemoattractant protein-1 regulation of blood-brain barrier permeability. J Cereb Blood Flow Metab. 2005;25:593-606.
Yu FPS, Dworski S, Medin JA. Deletion of MCP-1 impedes pathogenesis of acid ceramidase deficiency. Sci Rep. 2018;8:1808.
Bonsack F, Sukumari-Ramesh S. Differential cellular expression of galectin-1 and galectin-3 after intracerebral hemorrhage. Front Cell Neurosci. 2019;13:157.
Siew JJ, Chen HM, Chen HY, et al. Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington's disease. Nat Commun. 2019;10:3473.
Yip PK, Carrillo-Jimenez A, King P, et al. Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration. Sci Rep. 2017;7:41689.
Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury. Exp Neurol. 2013;246:35-43.
De Simoni S, Jenkins PO, Bourke NJ, et al. Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury. Brain. 2018;141:148-164.
Albert-Weissenberger C, Siren AL. Experimental traumatic brain injury. Exp Transl Stroke Med. 2010;2:16.
Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91:461-553.
Ramlackhansingh AF, Brooks DJ, Greenwood RJ, et al. Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol. 2011;70:374-383.
Smith C, Gentleman SM, Leclercq PD, et al. The neuroinflammatory response in humans after traumatic brain injury. Neuropathol Appl Neurobiol. 2013;39:654-666.
Brantley EC, Guo L, Zhang C, et al. Nitric oxide-mediated tumoricidal activity of murine microglial cells. Transl Oncol. 2010;3:380-388.
Morrison HW, Filosa JA. A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion. J Neuroinflammation. 2013;10:4.
Burguillos MA, Svensson M, Schulte T, et al. Microglia-secreted galectin-3 acts as a toll-like receptor 4 ligand and contributes to microglial activation. Cell Rep. 2015;10:1626-1638.
Reichert F, Rotshenker S. Galectin-3 (MAC-2) Controls Microglia Phenotype Whether Amoeboid and Phagocytic or Branched and Non-phagocytic by Regulating the Cytoskeleton. Front Cell Neurosci. 2019;13:90.
Budinich CS, Tucker LB, Lowe D, Rosenberger JG, McCabe JT. Short and long-term motor and behavioral effects of diazoxide and dimethyl sulfoxide administration in the mouse after traumatic brain injury. Pharmacol Biochem Behav. 2013;108:66-73.
Homsi S, Piaggio T, Croci N, et al. Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelve-week follow-up study. J Neurotrauma. 2010;27:911-921.
Kimbler DE, Shields J, Yanasak N, Vender JR, Dhandapani KM. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice. PLoS ONE. 2012;7:e41229.
Malkesman O, Tucker LB, Ozl J, McCabe JT. Traumatic brain injury-modeling neuropsychiatric symptoms in rodents. Front Neurol. 2013;4:157.
Ogier M, Belmeguenai A, Lieutaud T, et al. Cognitive deficits and inflammatory response resulting from mild-to-moderate traumatic brain injury in rats are exacerbated by repeated pre-exposure to an innate stress stimulus. J Neurotrauma. 2017;34:1645-1657.
Viggiano D. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity. Behav Brain Res. 2008;194:1-14.
Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988;1:623-634.
Faden AI, Demediuk P, Panter SS, Vink R. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science. 1989;244:798-800.
Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg. 1990;73:889-900.
Van Waes V, Beverley JA, Siman H, Tseng KY, Steiner H. CB1 cannabinoid receptor expression in the striatum: association with corticostriatal circuits and developmental regulation. Front Pharmacol. 2012;3:21.
Willuhn I, Sun W, Steiner H. Topography of cocaine-induced gene regulation in the rat striatum: relationship to cortical inputs and role of behavioural context. Eur J Neurosci. 2003;17:1053-1066.
Ujhelyi J, Ujhelyi Z, Szalai A, et al. Analgesic and anti-inflammatory effectiveness of sitagliptin and vildagliptin in mice. Regul Pept. 2014;194-195:23-29.
Mentlein R. Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul Pept. 1999;85:9-24.
Lankas GR, Leiting B, Roy RS, et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes. 2005;54:2988-2994.