LPS activates neuroinflammatory pathways to induce depression in Parkinson’s disease-like condition

Abstract

Aim: This study aimed to observe the effects of lipopolysaccharide (LPS) intraperitoneal (i.p.) injection on rats and investigate how neuroinflammation contributes to the pathogenesis of depression in Parkinson’s disease (dPD).Methods: Rats were administered LPS (0.5 mg/kg, i.p.) for either 1, 2, or 4 consecutive days to establish a rat model of dPD. The sucrose preference test (SPT), the open field test (OFT), and the rotarod test evaluated depression-like and motor behaviors. Magnetic resonance imaging was used to detect alterations in the intrinsic activity and the integrity of white matter fibers in the brain. The expression of c-Fos, ionized calcium-binding adapter molecule (Iba-1), and tyrosine hydroxylase (TH) was evaluated using immunohistochemistry. The concentration of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) was measured using Luminex technology.Results: LPS i.p. injections decreased sucrose preference in the SPT, horizontal and center distance in the OFT, and standing time in the rotarod test. The intrinsic activities in the hippocampus (HIP) were significantly reduced in the LPS-4 d group. The integrity of white matter fibers was greatly destroyed within 4 days of LPS treatment. The expression of c-Fos and Iba-1 in the prefrontal cortex, HIP, and substantia nigra increased dramatically, and the number of TH+ neurons in the substantia nigra decreased considerably after LPS injection. The levels of IL-6, TNF-α, and IL-10 were higher in the LPS-4 d group than those in the control group.Conclusion: Injection of LPS (0.5 mg/kg, i.p.) for 4 consecutive days can activate microglia, cause the release of inflammatory cytokines, reduce intrinsic activities in the HIP, destroy the integrity of white matter fibers, induce anhedonia and behavioral despair, and finally lead to dPD. This study proved that LPS injection (0.5 mg/kg, i.p.) for 4 consecutive days could be used to successfully create a rat model of dPD.

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson’s disease overexpressing human alpha synuclein

“…Similarly, the decreased DA release in LPS Snca +/+ rats did not alter the preference for a sweet-tasty solution, commonly used to assess the presence of a depressive- like behavior, such as anhedonia. In a recently published work, reduced sucrose consumption has been reported shortly after systemic LPS administration 46 . However, this condition could reflect a more acute phase in response to the LPS-induced inflammatory activation.…”

Compound Dihuang Granule Changes Gut Microbiota of MPTP-Induced Parkinson’s Disease Mice via Inhibiting TLR4/NF-κB Signaling

“…An open field test was conducted in 30 cm × 30 cm the observation box. Prior to the experiment, the mice habituated to their surroundings for 1 h. The mice were then set in the center of the open field reaction box, and the camera recorded the movement distances of mice for 5 min [ 21 ]. After the experiment, real-time video recording analyzed the distance from the center point and the residence time.…”

Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis

“…In specific, multiple psychosocial stressors have been demonstrated to accelerate the development of neuroinflammation and mental illness according to the clinical evidence [ 29 ]. Ongoing neuroinflammation could in turn induce depressive-like behaviors [ 30 , 31 ] or promote MDD progression [ 32 ]. Currently available antidepressants eliminate depressive symptoms for only 37% of MDD patients [ 33 ], together with an overall cumulative remission rate of 67% [ 33 ].…”