Anti-CA3 (aa 1-100) polyclonal antibody

Current evidence indicates that depression is accompanied by the activation of inflammatory response and oxidative stress. Protein arginine methyltransferase 1 (PRMT1) is a histone methyltransferase that methylates Arg3 on histone H4, playing crucial role in regulating various pathological processes. In the study, we attempted to explore the effects of PRMT1 on animal model with depression through a single administration of lipopolysaccharide (LPS). Our results indicated that PRMT1 knockout (PRMT1(-/-)) improved LPS-induced anxiety- and depressive-like behavior, along with up-regulated expression levels of brain-derived neurotrophic factor (BDNF) and PSD-95. Furthermore, PRMT1 deficiency significantly improved LPS-induced changes in dendritic spine density in the areas of prefrontal cortex (PFC), CA3 and dentate gyrus (DG), and nucleus accumbens (NAc). In addition, PRMT1 deletion ameliorated the neuroinflammatory responses, as evidenced by the reduced expression of interleukin 1 beta (IL 1 beta) and tumor necrosis factor (TNF)-alpha, which might be through repressing nuclear factor-KB (NF-kappa B) signaling. Moreover, oxidative stress induced by LPS was alleviated by PRMT1 knockout in hippocampus of mice at least partly via promoting Nrf-2 expressions. The anti-depressant effects of PRMT1 inhibition were verified in LPS-incubated astrocytes. Importantly, we found that PRMT1 knockout-alleviated inflammation and oxidative stress triggered by LPS were significantly recovered by the suppression of Nrf-2. Therefore, Nrf-2 was markedly involved in PRMT1-regulated depression-like behavior. Taken together, the results indicated that PRMT1 might be an important therapeutic target for developing effective treatment to prevent depressive-like behavior. (C) 2019 Published by Elsevier Inc.

OBJECTIVE The authors previously demonstrated that Cerebrolysin is effective for treatment of mild closed head injury (CHI) when administered 4 hours after injury. The aim of this study was to determine Cerebrolysin's effects on functional and histological outcomes in rats subjected to moderate CHI. METHODS In this randomized, blinded, and vehicle-controlled preclinical trial, male adult Wistar rats subjected to moderate CHI received either Cerebrolysin treatment at a dose of 2.5 ml/kg (n = 13) or vehicle (saline, n = 13) intraperitoneally administered daily for 10 days, starting at 4 hours after injury. Animals were subjected to cognitive and sensorimotor functional tests at multiple time points, and they were killed 3 months after injury. The brains were processed for analyses of neuronal cell loss, amyloid precursor protein, axonal damage, and neurogenesis. RESULTS Compared with rats treated with vehicle (saline), rats treated with Cerebrolysin had significantly increased numbers of neuroblasts and newborn mature neurons in the dentate gyrus (DG) and attenuated amyloid precursor protein accumulation and axonal damage in various brain regions, as well as decreased neuronal loss in the DG and cornu ammonis 3 (CA3) region of the hippocampus (p < 0.05). Global testing using generalized estimating equations showed a significant beneficial effect of Cerebrolysin treatment on sensorimotor functional outcomes from 1 day to 3 months after injury compared to that of saline treatment (p < 0.05). Compared with vehicle-treated rats, Cerebrolysin-treated rats showed significantly and robustly improved long-term (up to 3 months) cognitive functional recovery, as measured by social interaction, Morris water maze, novel object recognition, and odor recognition tests. In the Cerebrolysin-treated rats there were significant correlations between multiple histological outcomes and functional recovery evident 3 months after moderate CHI, as indicated by Pearson partial correlation analyses. CONCLUSIONS The authors' findings demonstrate that Cerebrolysin treatment significantly improves long-term functional and histological outcomes in rats with moderate CHI, with functional outcomes significantly correlated with histological indices of neuroplasticity and neuroprotection. These data indicate that Cerebrolysin may be useful for the treatment of moderate CHI.