Exercise increases mTOR signaling in brain regions involved in cognition and emotional behavior

Behavioural Brain Research

Volumn 323, Issue , 2017, Pages 56-67

  Lloyd, Brian A ^a   Hake, Holly S ^a   Ishiwata, Takayuki ^b   Farmer, Caroline E ^a   Loetz, Esteban C ^a   Fleshner, Monika ^c   Bland, Sondra T ^a   Greenwood, Benjamin N ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b RIKKYO UNIVERSITY   (Japan)

^c UNIVERSITY OF COLORADO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD11 ANTIGEN; GLIAL FIBRILLARY ACIDIC PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MTOR PROTEIN, RAT; TARGET OF RAPAMYCIN KINASE;

ADULT; AMYGDALA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BRAIN REGION; CELL COUNT; COGNITION; CONTROLLED STUDY; CORPUS STRIATUM; DENTATE GYRUS; EMOTIONALITY; ENZYME ANALYSIS; ENZYME LOCALIZATION; ENZYME PHOSPHORYLATION; EXERCISE; GLIA; HIPPOCAMPUS; HYPOTHALAMUS; IMMUNOHISTOCHEMISTRY; LEARNING; MALE; MEDIAL PREFRONTAL CORTEX; MICROGLIA; NERVE CELL; NONHUMAN; RAT; RUNNING; SEDENTARY LIFESTYLE; SIGNAL TRANSDUCTION; ANIMAL; BRAIN; EMOTION; FISCHER 344 RAT; METABOLISM; MOTOR ACTIVITY; PHOSPHORYLATION; PREFRONTAL CORTEX;

AMYGDALA; ANIMALS; BRAIN; COGNITION; CORPUS STRIATUM; EMOTIONS; HIPPOCAMPUS; HYPOTHALAMUS; MALE; MOTOR ACTIVITY; NEUROGLIA; NEURONS; PHOSPHORYLATION; PREFRONTAL CORTEX; RATS, INBRED F344; TOR SERINE-THREONINE KINASES;

EID: 85012254767     PISSN: 01664328     EISSN: 18727549     Source Type: Journal    
DOI: 10.1016/j.bbr.2017.01.033     Document Type: Article

References (119)

1. [1] Voss, M.W., et al. Exercise: brain, and cognition across the life span. J. Appl. Physiol. (1985) 111:5 (2011), 1505–1513.
2. [2] Gomez-Pinilla, F., Hillman, C., The influence of exercise on cognitive abilities. Compr. Physiol. 3:1 (2013), 403–428.
3. [3] Scudder, M.R., et al. Tracking the relationship between children's aerobic fitness and cognitive control. Health Psychol. 35:9 (2016), 967–978.
4. [4] Donnelly, J.E., et al. Physical activity, fitness, cognitive function, and academic achievement in children: a systematic review. Med. Sci. Sports Exerc. 48:6 (2016), 1223–1224.
5. [5] Solberg, L.C., Horton, T.H., Turek, F.W., Circadian rhythms and depression: effects of exercise in an animal model. Am. J. Physiol. 276:1 Pt 2 (1999), R152–61.
6. [6] Greenwood, B.N., et al. Freewheel running prevents learned helplessness/behavioral depression: role of dorsal raphe serotonergic neurons. J. Neurosci. 23:7 (2003), 2889–2898.
7. [7] Zheng, H., et al. Beneficial effects of exercise and its molecular mechanisms on depression in rats. Behav. Brain Res. 168:1 (2006), 47–55.
8. [8] Crabbe, J.B., Smith, J.C., Dishman, R.K., Emotional & electroencephalographic responses during affective picture viewing after exercise. Physiol. Behav. 90:2–3 (2007), 394–404.
9. [9] Blumenthal, J.A., et al. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom. Med. 69:7 (2007), 587–596.
10. [10] Cooney, G.M., et al. Exercise for depression. Cochrane Database Syst. Rev.(9), 2013 (p. CD004366).
11. [11] Takacs, J., Regular physical activity and mental health. The role of exercise in the prevention of: and intervention in depressive disorders. Psychiatr. Hung. 29:4 (2014), 386–397.
12. [12] Herring, M.P., O'Connor, P.J., Dishman, R.K., The effect of exercise training on anxiety symptoms among patients: a systematic review. Arch. Intern. Med. 170:4 (2010), 321–331.
13. [13] Sciolino, N.R., Holmes, P.V., Exercise offers anxiolytic potential: a role for stress and brain noradrenergic-galaninergic mechanisms. Neurosci. Biobehav. Rev. 36:9 (2012), 1965–1984.
14. [14] Powers, M.B., Asmundson, G.J., Smits, J.A., Exercise for mood and anxiety disorders: the state-of-the science. Cogn. Behav. Ther. 44:4 (2015), 237–239.
15. [15] Fordyce, D.E., Wehner, J.M., Physical activity enhances spatial learning performance with an associated alteration in hippocampal protein kinase C activity in C57BL/6 and DBA/2 mice. Brain Res. 619:1–2 (1993), 111–119.
16. [16] Ahmadiasl, N., Alaei, H., Hanninen, O., Effect of exercise on learning: memory and levels of epinephrine in rats' hippocampus. J. Sports Sci. Med. 2:3 (2003), 106–109.
17. [17] van Praag, H., et al. Exercise enhances learning and hippocampal neurogenesis in aged mice. J. Neurosci. 25:38 (2005), 8680–8685.
18. [18] Van der Borght, K., et al. Exercise improves memory acquisition and retrieval in the Y-maze task: relationship with hippocampal neurogenesis. Behav. Neurosci. 121:2 (2007), 324–334.
19. [19] Ang, E.T., et al. Alterations in spatial learning and memory after forced exercise. Brain Res. 1113:1 (2006), 186–193.
20. [20] Alaei, H., et al. Daily running promotes spatial learning and memory in rats. J. Sports Sci. Med. 6:4 (2007), 429–433.
21. [21] Berchtold, N.C., Castello, N., Cotman, C.W., Exercise and time-dependent benefits to learning and memory. Neuroscience 167:3 (2010), 588–597.
22. [22] Greenwood, B.N., et al. Exercise-induced stress resistance is independent of exercise controllability and the medial prefrontal cortex. Eur. J. Neurosci. 37:3 (2013), 469–478.
23. [23] Hall, M.N., mTOR-what does it do?. Transplant. Proc. 40:10 Suppl (2008), S5–8.
24. [24] Graber, T.E., McCamphill, P.K., Sossin, W.S., A recollection of mTOR signaling in learning and memory. Learn. Mem. 20:10 (2013), 518–530.
25. [25] Bergeron, Y., et al. mTOR signaling contributes to motor skill learning in mice. Front. Mol. Neurosci., 7, 2014, 26.
26. [26] Su, Z.W., et al. Postnatal high-protein diet improves learning and memory in premature rats via activation of mTOR signaling. Brain Res. 1611 (2015), 1–7.
27. [27] Sosanya, N.M., et al. Mammalian target of rapamycin (mTOR) tagging promotes dendritic branch variability through the capture of Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIalpha) mRNAs by the RNA-binding protein HuD. J. Biol. Chem. 290:26 (2015), 16357–16371.
28. [28] Slipczuk, L., et al. BDNF activates mTOR to regulate GluR1 expression required for memory formation. PLoS One, 4(6), 2009, e6007.
29. [29] Santini, E., Huynh, T.N., Klann, E., Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory. Prog. Mol. Biol. Transl. Sci. 122 (2014), 131–167.
30. [30] Jobim, P.F., et al. Inhibition of mTOR by rapamycin in the amygdala or hippocampus impairs formation and reconsolidation of inhibitory avoidance memory. Neurobiol. Learn Mem. 97:1 (2012), 105–112.
31. [31] Speisman, R.B., et al. Daily exercise improves memory, stimulates hippocampal neurogenesis and modulates immune and neuroimmune cytokines in aging rats. Brain Behav. Immun. 28 (2013), 25–43.
32. [32] Fernandes, J., et al. Aerobic exercise attenuates inhibitory avoidance memory deficit induced by paradoxical sleep deprivation in rats. Brain Res. 1529 (2013), 66–73.
33. [33] Lovatel, G.A., et al. Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus. Neurobiol. Learn. Mem. 101 (2013), 94–102.
34. [34] Liu, L., et al. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene 25:53 (2006), 7029–7040.
35. [35] McAuliffe, P.F., et al. Deciphering the role of PI3 K/Akt/mTOR pathway in breast cancer biology and pathogenesis. Clin. Breast Cancer 10:Suppl. 3 (2010), S59–65.
36. [36] Dwyer, J.M., et al. Ribosomal protein S6 kinase 1 signaling in prefrontal cortex controls depressive behavior. Proc. Natl. Acad. Sci. U. S. A. 112:19 (2015), 6188–6193.
37. [37] Hullinger, R., O'Riordan, K., Burger, C., Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k. Neurobiol. Learn. Mem. 125 (2015), 126–134.
38. [38] Cook, S.C., Wellman, C.L., Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J. Neurobiol. 60:2 (2004), 236–248.
39. [39] Radley, J.J., et al. Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125:1 (2004), 1–6.
40. [40] Li, N., et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:5994 (2010), 959–964.
41. [41] Sen, S., et al. Glucose regulation of load-induced mTOR signaling and ER stress in mammalian heart. J. Am. Heart Assoc., 2(3), 2013, e004796.
42. [42] Nave, B.T., et al. Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation. Biochem. J. 344:Pt 2 (1999), 427–431.
43. [43] Hara, K., et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273:23 (1998), 14484–14494.
44. [44] Oshiro, N., Rapley, J., Avruch, J., Amino acids activate mammalian target of rapamycin (mTOR) complex 1 without changing rag GTPase guanyl nucleotide charging. J. Biol. Chem. 289:5 (2014), 2658–2674.
45. [45] Bergstrom, J., Furst, P., Hultman, E., Free amino acids in muscle tissue and plasma during exercise in man. Clin. Physiol. 5:2 (1985), 155–160.
46. [46] Peake, J.M., et al. Metabolic and hormonal responses to isoenergetic high-intensity interval exercise and continuous moderate-intensity exercise. Am. J. Physiol. Endocrinol. Metab. 307:7 (2014), E539–52.
47. [47] Melancon, M.O., Lorrain, D., Dionne, I.J., Exercise increases tryptophan availability to the brain in older men age 57–70 years. Med. Sci. Sports Exerc. 44:5 (2012), 881–887.
48. [48] Takei, N., et al. Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites. J. Neurosci. 24:44 (2004), 9760–9769.
49. [49] Zhou, J.X., et al. TNFalpha signaling regulates cystic epithelial cell proliferation through Akt/mTOR and ERK/MAPK/Cdk2 mediated Id2 signaling. PLoS One, 10(6), 2015, e0131043.
50. [50] Ying, Z., et al. BDNF-exercise interactions in the recovery of symmetrical stepping after a cervical hemisection in rats. Neuroscience 155:4 (2008), 1070–1078.
51. [51] Vary, T.C., Lang, C.H., IGF-I activates the eIF4F system in cardiac muscle in vivo. Mol. Cell. Biochem. 272:1–2 (2005), 209–220.
52. [52] Starkman, B.G., et al. IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK. Biochem. J. 389:Pt 3 (2005), 723–729.
53. [53] Intlekofer, K.A., et al. Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism. Neuropsychopharmacology 38:10 (2013), 2027–2034.
54. [54] Church, D.D., et al. L-Leucine increases skeletal muscle IGF-1 but does not differentially increase Akt/mTORC1 signaling and serum IGF-1 compared to ursolic acid in response to resistance exercise in resistance-Trained men. J. Am. Coll. Nutr. 2016 (2016), 1–12.
55. [55] Vaynman, S., Ying, Z., Gomez-Pinilla, F., Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur. J. Neurosci. 20:10 (2004), 2580–2590.
56. [56] Duman, C.H., et al. Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise. Behav. Brain Res. 198:2 (2009), 366–371.
57. [57] Minichiello, L., et al. Mechanism of TrkB-mediated hippocampal long-term potentiation. Neuron 36:1 (2002), 121–137.
58. [58] Huber, K.M., Kayser, M.S., Bear, M.F., Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression. Science 288:5469 (2000), 1254–1257.
59. [59] Jourdi, H., et al. Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J. Neurosci. 29:27 (2009), 8688–8697.
60. [60] Watson, K., Baar, K., mTOR and the health benefits of exercise. Semin. Cell Dev. Biol. 36 (2014), 130–139.
61. [61] Elfving, B., et al. Transient activation of mTOR following forced treadmill exercise in rats. Synapse 67:9 (2013), 620–625.
62. [62] Fang, Z.H., et al. Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats. Neurosci. Res. 76:4 (2013), 187–194.
63. [63] E.L, Burns, J.M., Swerdlow, R.H., Effect of high-intensity exercise on aged mouse brain mitochondria, neurogenesis, and inflammation. Neurobiol. Aging 35:11 (2014), 2574–2583.
64. [64] Alaei, H., Moloudi, R., Sarkaki, A.R., Effects of treadmill running on mid-term memory and swim speed in the rat with Morris water maze test. J. Bodyw. Mov. Ther. 12:1 (2008), 72–75.
65. [65] Wang, X.Q., Wang, G.W., Effects of treadmill exercise intensity on spatial working memory and long-term memory in rats. Life Sci. 149 (2016), 96–103.
66. [66] Greenwood, B.N., Fleshner, M., Exercise, stress resistance, and central serotonergic systems. Exerc. Sport Sci. Rev. 39:3 (2011), 140–149.
67. [67] Chen, C., et al. The role of medial prefrontal corticosterone and dopamine in the antidepressant-like effect of exercise. Psychoneuroendocrinology 69 (2016), 1–9.
68. [68] Cunha, M.P., et al. The antidepressant-like effect of physical activity on a voluntary running wheel. Med. Sci. Sports Exerc. 45:5 (2013), 851–859.
69. [69] Duman, C.H., et al. Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice. Brain Res. 1199 (2008), 148–158.
70. [70] Herrera, J.J., et al. Neurochemical and behavioural indices of exercise reward are independent of exercise controllability. Eur. J. Neurosci. 43:9 (2016), 1190–1202.
71. [71] Greenwood, B.N., et al. Voluntary freewheel running selectively modulates catecholamine content in peripheral tissue and c-Fos expression in the central sympathetic circuit following exposure to uncontrollable stress in rats. Neuroscience 120:1 (2003), 269–281.
72. [72] Greenwood, B.N., et al. Long-term voluntary wheel running is rewarding and produces plasticity in the mesolimbic reward pathway. Behav. Brain Res. 217:2 (2011), 354–362.
73. [73] Duman, R.S., et al. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology 62:1 (2012), 35–41.
74. [74] Chong, Z.Z., et al. Mammalian target of rapamycin: hitting the bull's-eye for neurological disorders. Oxid. Med. Cell Longev. 3:6 (2010), 374–391.
75. [75] Shi, D., et al. Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells. Int. J. Nanomed. 11 (2016), 5823–5835.
76. [76] Sarfstein, R., et al. The mechanism of action of the histone deacetylase inhibitor vorinostat involves interaction with the insulin-Like growth factor signaling pathway. PLoS One, 2011 Online.
77. [77] Shang, J., et al. Antiapoptotic and antiautophagic effects of glial cell line-derived neurotrophic factor and hepatocyte growth factor after transient middle cerebral artery occlusion in rats. J. Neurosci. Res. 88:10 (2010), 2197–2206.
78. [78] Fu, L., et al. Inhibition of AMP-activated protein kinase alleviates focal cerebral ischemia injury in mice: interference with mTOR and autophagy. Brain Res. 1650 (2016), 103–111.
79. [79] Nonoda, Y., et al. Activation of microglia/macrophages expressing phosphorylated S6 ribosomal protein in a case of hemimegalencephaly with progressive calcification and atrophy. J. Neurol. Sci. 287:1–2 (2009), 52–59.
80. [80] Dreyer, H.C., et al. Resistance exercise increases leg muscle protein synthesis and mTOR signalling independent of sex. Acta Physiol. (Oxf.) 199:1 (2010), 71–81.
81. [81] Mascher, H., et al. Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects. Acta Physiol. (Oxf.) 202:2 (2011), 175–184.
82. [82] Garza-Lombo, C., Gonsebatt, M.E., Mammalian target of rapamycin: its role in early neural development and in adult and aged brain function. Front. Cell. Neurosci., 10, 2016, p157.
83. [83] Noble, E.E., et al. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons. Neurobiol. Learn. Mem. 114 (2014), 40–50.
84. [84] Soya, H., et al. BDNF induction with mild exercise in the rat hippocampus. Biochem. Biophys. Res. Commun. 358:4 (2007), 961–967.
85. [85] Hong, Y.P., Lee, H.C., Kim, H.T., Treadmill exercise after social isolation increases the levels of NGF: BDNF, and synapsin I to induce survival of neurons in the hippocampus, and improves depression-like behavior. J. Exerc. Nutr. Biochem. 19:1 (2015), 11–18.
86. [86] Lambert, K.G., The activity-stress paradigm: possible mechanisms and applications. J. Gen. Psychol. 120:1 (1993), 21–32.
87. [87] Lambert, K.G., et al. Activity-stress induces atrophy of apical dendrites of hippocampal pyramidal neurons in male rats. Physiol. Behav. 65:1 (1998), 43–49.
88. [88] Sengupta, S., Peterson, T.R., Sabatini, D.M., Regulation of the mTOR complex 1 pathway by nutrients: growth factors, and stress. Mol. Cell 40:2 (2010), 310–322.
89. [89] Sun, P., et al. Anger emotional stress influences VEGF/VEGFR2 and its induced PI3 K/AKT/mTOR signaling pathway. Neural Plast., 2016, 2016, 4129015.
90. [90] Ochi, E., Ishii, N., Nakazato, K., Time course change of IGF1/Akt/mTOR/p70s6k pathway activation in rat gastrocnemius muscle during repeated bouts of eccentric exercise. J. Sports Sci. Med. 9:2 (2010), 170–175.
91. [91] Ross, C.E., Hayes, D., Exercise and psychologic well-being in the community. Am. J. Epidemiol. 127:4 (1988), 762–771.
92. [92] McCann, I.L., Holmes, D.S., Influence of aerobic exercise on depression. J. Pers. Soc. Psychol. 46:5 (1984), 1142–1147.
93. [93] Babyak, M., et al. Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom. Med. 62:5 (2000), 633–638.
94. [94] Tuon, T., et al. Physical training prevents depressive symptoms and a decrease in brain-derived neurotrophic factor in Parkinson's disease. Brain Res. Bull. 108 (2014), 106–112.
95. [95] Han, L.N., et al. Activation of serotonin(2C) receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat. Neuropharmacology 93 (2015), 68–79.
96. [96] Martinsen, E.W., Physical activity and depression: clinical experience. Acta Psychiatr. Scand. Suppl. 377 (1994), 23–27.
97. [97] Stenman, E., Lilja, A., Increased monoaminergic neurotransmission improves compliance with physical activity recommendations in depressed patients with fatigue. Med. Hypotheses 80:1 (2013), 47–49.
98. [98] Christianson, J.P., Greenwood, B.N., Stress-protective neural circuits: not all roads lead through the prefrontal cortex. Stress 17:1 (2014), 1–12.
99. [99] Dadalko, O.I., et al. mTORC2/rictor signaling disrupts dopamine-dependent behaviors via defects in striatal dopamine neurotransmission. J. Neurosci. 35:23 (2015), 8843–8854.
100. [100] Mustroph, M.L., et al. Wheel running can accelerate or delay extinction of conditioned place preference for cocaine in male C57BL/6J mice: depending on timing of wheel access. Eur. J. Neurosci. 34:7 (2011), 1161–1169.
101. [101] Ehringer, M.A., Hoft, N.R., Zunhammer, M., Reduced alcohol consumption in mice with access to a running wheel. Alcohol 43:6 (2009), 443–452.
102. [102] Smith, M.A., et al. Acute bouts of wheel running decrease cocaine self-administration: influence of exercise output. Pharmacol. Biochem. Behav. 150–151 (2016), 94–99.
103. [103] Foley, T.E., Fleshner, M., Neuroplasticity of dopamine circuits after exercise: implications for central fatigue. Neuromol. Med. 10:2 (2008), 67–80.
104. [104] Greenwood, B.N., et al. 5-HT2C receptors in the basolateral amygdala and dorsal striatum are a novel target for the anxiolytic and antidepressant effects of exercise. PLoS One, 7(9), 2012, e46118.
105. [105] Neeper, S.A., et al. Exercise and brain neurotrophins. Nature, 373(6510), 1995, 109.
106. [106] Hopkins, M.E., Bucci, D.J., BDNF expression in perirhinal cortex is associated with exercise-induced improvement in object recognition memory. Neurobiol. Learn. Mem. 94:2 (2010), 278–284.
107. [107] Fahey, B., et al. Interferon-alpha-induced deficits in novel object recognition are rescued by chronic exercise. Physiol. Behav. 95:1–2 (2008), 125–129.
108. [108] Morrison, S.F., Central control of body temperature. F1000Res, 5, 2016.
109. [109] Morrison, S.F., Nakamura, K., Central neural pathways for thermoregulation. Front. Biosci. (Landmark Ed.) 16 (2011), 74–104.
110. [110] Hu, F., Xu, Y., Liu, F., Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis. Am. J. Physiol. Endocrinol. Metab. 310:11 (2016), E994–E1002.
111. [111] Rowsey, P.J., Metzger, B.L., Gordon, C.J., Effects of exercise conditioning on thermoregulatory response to anticholinesterase insecticide toxicity. Biol. Res. Nurs. 2:4 (2001), 267–276.
112. [112] Rowsey, P.J., et al. Effects of exercise conditioning on thermoregulatory responses to repeated administration of chlorpyrifos. Environ. Res. 92:1 (2003), 27–34.
113. [113] Thompson, R.S., et al. Wheel running improves REM sleep and attenuates stress-induced flattening of diurnal rhythms in F344 rats. Stress 19:3 (2016), 312–324.
114. [114] Lalo, U., Rasooli-Nejad, S., Pankratov, Y., Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging. Biochem. Soc. Trans. 42:5 (2014), 1275–1281.
115. [115] Takemoto, T., et al. Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury. Environ. Toxicol. Pharmacol. 40:1 (2015), 199–205.
116. [116] Ji, Y.F., et al. Upregulation of glutamate transporter GLT-1 by mTOR-Akt-NF-small ka: cyrillicB cascade in astrocytic oxygen-glucose deprivation. Glia 61:12 (2013), 1959–1975.
117. [117] Lisi, L.et al., The mTOR kinase inhibitor rapamycin decreases iNOS mRNA stability in astrocytes. J. Neuroinflamm., 8(1), 2011, 1.
118. [118] Song, Q., et al. Rapamycin protects neurons from brain contusioninduced inflammatory reaction via modulation of microglial activation. Mol. Med. Rep. 12:5 (2015), 7203–7210.
119. [119] Tateda, S., et al. Rapamycin suppresses microglial activation and reduces the development of neuropathic pain after spinal cord injury. J. Orthop. Res., 2016.