The Cox-2 Inhibitor Meloxicam Ameliorates Neuroinflammation and Depressive Behavior in Adult Mice after Splenectomy.

Autor:	Haile M; Department of Anesthesiology, New York University School of Medicine., Boutajangout A; Department of Neurology, New York University School of Medicine; Department of Psychiatry, New York University School of Medicine; Department of Physiology, Neuroscience, New York, New York; King Abdulaziz University, Jeddah, Saudi Arabia., Chung K; Department of Anesthesiology, New York University School of Medicine., Chan J; Department of Anesthesiology, New York University School of Medicine., Stolper T; Department of Anesthesiology, New York University School of Medicine., Vincent N; Department of Anesthesiology, New York University School of Medicine., Batchan M; Department of Anesthesiology, New York University School of Medicine., D'Urso J; Department of Anesthesiology, New York University School of Medicine., Lin Y; Department of Psychiatry, New York University School of Medicine., Kline R; Department of Anesthesiology, New York University School of Medicine., Yaghmoor F; Department of Neurology, New York University School of Medicine., Jahfal S; Department of Neurology, New York University School of Medicine., Kamal R; Department of Neurology, New York University School of Medicine., Aljohani W; Department of Neurology, New York University School of Medicine., Blanck T; Department of Anesthesiology, New York University School of Medicine., Bekker A; Rutgers New Jersey Medical School, New York University School of Medicine, New Jersey., Wisniewski T; Department of Neurology, New York University School of Medicine; Department of Psychiatry, New York University School of Medicine; Department of Pathology, New York University School of Medicine.
Jazyk:	angličtina
Zdroj:	Journal of neurophysiology and neurological disorders [J Neurophysiol Neurol Disord] 2016; Vol. 3. Date of Electronic Publication: 2016 Aug 05.
Abstrakt:	Background: Peripheral surgical trauma may incite neuroinflammation that leads to neuronal dysfunction associated with both depression and cognitive deficits. In a previous study, we found that adult mice developed neuroinflammation and short-term working memory dysfunction in a delayed, transient manner after splenectomy that was ameliorated by the cyclooxygenase-2 inhibitor meloxicam. We tested the hypothesis that splenectomy in mice would also cause anhedonia, the diminished response to pleasure or rewarding stimuli that is a hallmark of depression, and that treatment with meloxicam would be ameliorative. Methods: After Institutional Animal Care and Use Committee approval, Swiss-Webster mice underwent sucrose preference training before being randomized into groups on day 0, when they had either splenectomy and anesthesia or anesthesia alone. Within each group, half were randomized to receive intraperitoneal saline at 24 hours, while the other half received intraperitoneal meloxicam at 24 hours. Sucrose preference ratios were determined on days 1, 5, 9, and 14. Additional mice were randomized into groups for brain histochemistry. Specimens were stained for glial fibrillary acidic protein (GFAP), a marker of astrocytes, and CD45, a protein tyrosine phosphatase that identifies microglial activation. Results: On day 5, mice receiving splenectomy and saline demonstrated diminished sucrose preference, which was not seen in mice receiving splenectomy and meloxicam. Semiquantitative analysis of histological slides taken from splenectomized mice treated with meloxicam revealed reduced microglial-based neuroinflammation and reactive astrocytosis compared to mice receiving saline. Conclusion: Splenectomy in mice is associated with neuroinflammation and anhedonia, as evidenced by reactive microgliosis, astrocytosis, and behavioral changes. Postsurgical treatment with meloxicam attenuates both neuroinflammation and anhedonia. These findings suggest that cyclooxygenase-2-dependent mechanisms may play a role in the development of postoperative mood disorders, possibly via modulation of peripheral effects on neuroinflammation. Competing Interests: None of the authors have any conflicts of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu