Background: The components of the immune system have been indicated to be linked with the neurotoxicity in Alzheimer's disease (AD). The participation of the immune system in the neurodegeneration in a rat model of colchicine-induced AD has not been explored. Methods: In the present study, hippocampal neurodegeneration along with reactive oxygen species (ROS), nitrite and TNF-α in the hippocampus and some systemic immune responses were measured after 15 and 21 days of intracerebroventricular colchicine injection in rats and again after oral administration of different doses of the anti-inflammatory drug naproxen in AD rats. Results: Chromatolysis and amyloid plaques were found along with higher ROS, nitrite and TNF-α levels in the hippocampus of colchicine-induced AD rats, and these changes were prevented by naproxen in a dose-dependent manner. Alterations in immunological parameters [increased phagocytic activity of white blood cells and splenic polymorphonuclear cells (PMN), increased cytotoxicity and decreased leucocyte adhesive inhibition index (LAI) of splenic mononuclear cells (MNC)] were also observed in colchicine-injected rats, which showed a dose-dependent recovery after oral administration of naproxen in AD rats. The number of plaques, chromatolysis of Nissl granules, TNF-α, nitrite and ROS levels in the hippocampus, phagocytic activity of splenic PMN and LAI of splenic MNC in AD rats showed greater changes in the 21- than in the 15-day study, and the recovery of these parameters after administration of naproxen differed between the two study durations. Conclusion: The present study shows that colchicine-induced neurodegeneration is time dependent and mediated by cyclooxygenase-induced neuroinflammation, which is reflected in the systemic immunological responses.

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Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS.