Page 137 - Read Online
P. 137
such as ketamine [38] as well as selective serotonin Jr. Improvement in suicidal ideation after ketamine infusion:
reuptake inhibitors [39] and tricyclic [40,41] may reverse relationship to reductions in depression and anxiety. J Psychiatr
the neurodegenerative activation of microglia induced 9. Res 2014;58:161‑6.
Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR,
by pathologically increased inflammatory cytokines. Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B.
Microglia sculpt postnatal neural circuits in an activity and
Furthermore, increased glucocorticoids levels may complement‑dependent manner. Neuron 2012;74:691‑705.
affect the integrity of microglial cells in the early phases 10. Serafini G, Pompili M, Elena Seretti M, Stefani H, Palermo M, Coryell W,
Girardi P. The role of inflammatory cytokines in suicidal behavior: a
of depression. [42] Abnormal extracellular glutamate systematic review. Eur Neuropsychopharmacol 2013;23:1672‑86.
concentrations may spill into microglial cells exerting 11. Frick LR, Williams K, Pittenger C. Microglial dysregulation in
neurotoxic effects on γ-aminobutyric acid neurons. [43] psychiatric disease. Clin Dev Immunol 2013;2013:608654.
The uptake of glutamate is progressively decreased, 12. Blank T, Prinz M. Microglia as modulators of cognition and
neuropsychiatric disorders. Glia 2013;61:62‑70.
and the density of glutamatergic pyramidal neurons 13. Frank MG, Baratta MV, Sprunger DB, Watkins LR, Maier SF.
is reduced in depressed individuals [44] with the final Microglia serve as a neuroimmune substrate for stress‑induced
result of reduced cortical levels of glutamate in the later potentiation of CNS pro‑inflammatory cytokine responses. Brain
phases of depression. Behav Immun 2007;21:47‑59.
14. Hanisch UK. Microglia as a source and target of cytokines. Glia
2002;40:140‑55.
Overall, microglial cells are able to exert significant 15. David S, Kroner A. Repertoire of microglial and macrophage
immunomodulatory functions in the central nervous responses after spinal cord injury. Nat Rev Neurosci 2011;12:388‑99.
system. Structural changes induced by chronic 16. Hinwood M, Morandini J, Day TA, Walker FR. Evidence
stress and MDD on glial cells may contribute to the that microglia mediate the neurobiological effects of chronic
psychological stress on the medial prefrontal cortex. Cereb Cortex
pathophysiology of these conditions, but they may be 2012;22:1442‑54.
significantly reversed using modern antidepressant 17. Arakawa S, Shirayama Y, Fujita Y, Ishima T, Horio M, Muneoka K,
medications. Aberrant levels of quinolinic acid Iyo M, Hashimoto K. Minocycline produced antidepressant‑like
produced by abnormal pathways inside microglia effects on the learned helplessness rats with alterations in levels
of monoamine in the amygdala and no changes in BDNF levels
cells represent a valid intracellular mediator of in the hippocampus at baseline. Pharmacol Biochem Behav
pathologically inflammatory- and glutamatergic-related 2012;100:601‑6.
changes. A complex interaction between dysfunctional 18. Bayer TA, Buslei R, Havas L, Falkai P. Evidence for activation
inflammatory pathways, increased oxidative stress, of microglia in patients with psychiatric illnesses. Neurosci Lett
1999;271:126‑8.
altered neuroplasticity in glial cells and neuronal 19. Steiner J, Mawrin C, Ziegeler A, Bielau H, Ullrich O, Bernstein HG,
abnormalities are involved in both MDD and suicidal Bogerts B. Distribution of HLA‑DR‑positive microglia in schizophrenia
behavior. reflects impaired cerebral lateralization. Acta Neuropathol
2006;112:305‑16.
20. Steiner J, Bielau H, Brisch R, Danos P, Ullrich O, Mawrin C,
REFERENCES Bernstein HG, Bogerts B. Immunological aspects in the neurobiology
of suicide: elevated microglial density in schizophrenia and
1. Greer TL, Kurian BT, Trivedi MH. Defining and measuring functional depression is associated with suicide. J Psychiatr Res 2008;42:151‑7.
recovery from depression. CNS Drugs 2010;24:267‑84. 21. Dean B, Gibbons AS, Tawadros N, Brooks L, Everall IP, Scarr E.
2. Serafini G, Pompili M, Innamorati M, Dwivedi Y, Brahmachari G, Different changes in cortical tumor necrosis factor‑a‑related
Girardi P. Pharmacological properties of glutamatergic drugs pathways in schizophrenia and mood disorders. Mol Psychiatry
targeting NMDA receptors and their application in major depression. 2013;18:767‑73.
Curr Pharm Des 2013;19:1898‑922. 22. Niciu MJ, Henter ID, Sanacora G, Zarate CA Jr. Glial abnormalities in
3. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, substance use disorders and depression: does shared glutamatergic
Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, dysfunction contribute to comorbidity? World J Biol Psychiatry
Shores‑Wilson K, Biggs MM, Balasubramani GK, Fava M. 2014;15:2‑16.
Evaluation of outcomes with citalopram for depression using 23. Crews FT, Vetreno RP. Addiction, adolescence, and innate immune
measurement‑based care in STAR*D: implications for clinical gene induction. Front Psychiatry 2011;2:19.
practice. Am J Psychiatry 2006;163:28‑40. 24. Maes M, Fišar Z, Medina M, Scapagnini G, Nowak G, Berk M. New
4. Rihmer Z, Gonda X. Antidepressant‑resistant depression and drug targets in depression: inflammatory, cell‑mediated immune,
antidepressant‑associated suicidal behaviour: the role of underlying oxidative and nitrosative stress, mitochondrial, antioxidant, and
bipolarity. Depress Res Treat 2011;2011:906462. neuroprogressive pathways. And new drug candidates – Nrf2
5. Sanacora G, Treccani G, Popoli M. Towards a glutamate hypothesis activators and GSK‑3 inhibitors. Inflammopharmacology
of depression: an emerging frontier of neuropsychopharmacology 2012;20:127‑50.
for mood disorders. Neuropharmacology 2012;62:63‑77. 25. Diamond B, Volpe BT. A model for lupus brain disease. Immunol
6. Yüksel C, Öngür D. Magnetic resonance spectroscopy studies of Rev 2012;248:56‑67.
glutamate‑related abnormalities in mood disorders. Biol Psychiatry 26. Faust TW, Chang EH, Kowal C, Berlin R, Gazaryan IG, Bertini E,
2010;68:785‑94. Zhang J, Sanchez‑Guerrero J, Fragoso‑Loyo HE, Volpe BT,
7. Niciu MJ, Luckenbaugh DA, Ionescu DF, Guevara S, Diamond B, Huerta PT. Neurotoxic lupus autoantibodies alter brain
Machado‑Vieira R, Richards EM, Brutsche NE, Nolan NM, Zarate function through two distinct mechanisms. Proc Natl Acad Sci U S
CA Jr. Clinical predictors of ketamine response in treatment‑resistant A 2010;107:18569‑74.
major depression. J Clin Psychiatry 2014;75:e417‑23. 27. Santello M, Bezzi P, Volterra A. TNFa controls glutamatergic
8. Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, gliotransmission in the hippocampal dentate gyrus. Neuron
Luckenbaugh DA, Brutsche NE, Ameli R, Furey ML, Zarate CA 2011;69:988‑1001.
128 Neuroimmunol Neuroinflammation | Volume 2 | Issue 3 | July 15, 2015 Neuroimmunol Neuroinflammation | Volume 2 | Issue 3 | July 15, 2015 129