Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation.

OBJECTIVE: This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury (SCI) in the central nervous system (CNS) and its mechanism in promoting the structural and functional recovery of the injured CNS. METHODS: A compressive SCI mouse model was utilized for this investigation. Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein, acrolein-induced inflammation-related factors, and macrophages at the injury site and within the CNS. Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase (PI3K)/AKT pathway to study macrophage regulation. The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67 (GAD65/67), vesicular glutamate transporter 1 (VGLUT1), paw withdrawal response, and Basso Mouse Scale score. Nissl staining and Luxol Fast Blue (LFB) staining were performed to investigate the structural recovery of the injured CNS. RESULTS: Hydralazine downregulated the levels of acrolein, IL-1ß, and TNF-α in the spinal cord. The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway, leading to M2 macrophage polarization, which protected neurons against SCI-induced inflammation. Additionally, hydralazine promoted the structural recovery of the injured spinal cord area. Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression. Furthermore, hydralazine facilitated motor function recovery following SCI. Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS. CONCLUSION: Hydralazine, an acrolein scavenger, significantly mitigated SCI-induced inflammation and oxidative stress in vivo, modulated macrophage activation, and consequently promoted the structural and functional recovery of the injured CNS.

Life Table Construction under Different Temperatures and Insecticide Susceptibility Analysis of Uroleucon formosanum (Hemiptera: Aphididae).

Uroleucon formosanum is an important aphid pest of lettuce, but basic information on its biology is scarce. In this study, effects of three constant temperatures (17, 21, and 25 °C, simulating the mean temperature range in greenhouses) on the development and fecundity of U. formosanum were analyzed by constructing a life table. U. formosanum could develop and reproduce under all three temperatures, but the survival rate, development, and fecundity of U. formosanum were affected by temperature. The intrinsic rate of increase was lowest at 17 °C (0.17) and it was significantly less than at 21 °C (0.20) and 25 °C (0.23). Furthermore, U. formosanum had the lowest finite rate of increase (1.19) and the largest mean generation time (20.21) at 17 °C. These results mean that U. formosanum is less adapted to the lower temperatures (17 °C) among these three set temperatures. To screen insecticides for control, susceptibility of U. formosanum to six insecticides including chlorpyrifos, abamectin, beta-cypermethrin, imidacloprid, nitenpyram, and thiamethoxam was evaluated. U. formosanum was relatively sensitive to all six test insecticides. Chlorpyrifos had the highest toxicity to U. formosanum (LC50 = 3.08 mg/L). These data may help to develop integrated management strategies for better population control of U. formosanum.

Interaction of basolateral amygdala, ventral hippocampus and medial prefrontal cortex regulates the consolidation and extinction of social fear.

BACKGROUND: Following a social defeat, the balanced establishment and extinction of aversive information is a beneficial strategy for individual survival. Abnormal establishment or extinction is implicated in the development of mental disorders. This study investigated the time course of the establishment and extinction of aversive information from acute social defeat and the temporal responsiveness of the basolateral amygdala (BLA), ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) in this process. METHODS: Mouse models of acute social defeat were established by using the resident-intruder paradigm. To evaluate the engram of social defeat, the intruder mice were placed into the novel context at designated time to test the social behavior. Furthermore, responses of BLA, vHIP and mPFC were investigated by analyzing the expression of immediate early genes, such as zif268, arc, and c-fos. RESULTS: The results showed after an aggressive attack, aversive memory was maintained for approximately 7 days before gradually diminishing. The establishment and maintenance of aversive stimulation were consistently accompanied by BLA activity. By contrast, vHIP and mPFC response was inhibited from this process. Additionally, injecting muscimol (Mus), a GABA receptor agonist, into the BLA alleviated the freezing behavior and social fear and avoidance. Simultaneously, Mus treatment decreased the zif268 and arc expression in BLA, but it increased their expression in vHIP. CONCLUSION: Our data support and extend earlier findings that implicate BLA, vHIP and mPFC in social defeat. The time courses of the establishment and extinction of social defeat are particularly consistent with the contrasting BLA and vHIP responses involved in this process.

Adult neural stem cell dysfunction in the subventricular zone of the lateral ventricle leads to diabetic olfactory defects.

Sensitive smell discrimination is based on structural plasticity of the olfactory bulb, which depends on migration and integration of newborn neurons from the subventricular zone. In this study, we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus. Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats. Two months after injection, olfactory sensitivity was decreased in diabetic rats. Meanwhile, the number of BrdU-positive and BrdU+/DCX+ double-labeled cells was lower in the subventricular zone of diabetic rats compared with age-matched normal rats. Western blot results revealed downregulated expression of insulin receptor ß, phosphorylated glycogen synthase kinase 3ß, and ß-catenin in the subventricular zone of diabetic rats. Altogether, these results indicate that diabetes mellitus causes insulin deficiency, which negatively regulates glycogen synthase kinase 3ß and enhances ß-catenin degradation, with these changes inhibiting neural stem cell proliferation. Further, these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone. Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.

Role of Arcuate Nucleus in the Regulation of Feeding Behavior in the Process of Altitude Acclimatization in Rats.

Liu, Xiang-Wen, Jie Yin, Qi-Sheng Ma, Chu-Chu Qi, Ji-Ying Mu, Lang Zhang, Li-Ping Gao, and Yu-Hong Jing. Role of arcuate nucleus in the regulation of feeding behavior in the process of altitude acclimatization in rats. High Alt Med Biol. 18:234-241, 2017.-Highly efficient energy utilization and metabolic homeostasis maintenance rely on neuromodulation. Altitude exposure is known to stimulate neuroendocrine systems to respond to acute hypoxia and adaptive acclimatization. However, limited data on how the adaptive regulation of the arcuate nucleus performs in the process of altitude acclimatization are available. In the present study, male Sprague Dawley rats were transported to Huashixia, Qinghai (with an altitude of 4400 m) from Xian (with an altitude of 300 m) by air; rats were consistently raised in Xian as control. Food uptake and body weight were measured consecutively after being subjected to high-altitude condition. Contents of plasma leptin and ghrelin were analyzed by the Enzyme Linked Immunosorbent Assay (ELISA) Kits. Brain coronal sections were obtained, and neuropeptide Y (NPY), proopiomelanocotin (POMC), and c-fos immunoreactivity in arcuate nucleus were observed. Arcuate nucleus was isolated from the hypothalamus, and the mRNA of NPY and POMC were measured by quantitative real-time polymerase chain reaction. Our results showed both food consumption and body weight decreased in the high plateau compared with rats raised in the low-altitude condition. Plasma leptin increased at the early stage, and ghrelin decreased at a later stage after reaching the high plateau. The peak of c-fos immunoreactivity in the arcuate nucleus was at day 3 after reaching the high plateau. The expression level of NPY increased, and POMC decreased in the arcuate nucleus at day 7 after reaching the high plateau compared with the plain control group. These results indicate that the arcuate nucleus of hypothalamus performs an important function in regulating feeding behavior during altitude acclimatization. Our study suggested that altitude acclimation is regulated by the hypothalamus that received leptin and ghrelin signals to response by its microcircuit, including NPY- and POMC-neurons in the arcuate nucleus.

Autophagy plays beneficial effect on diabetic encephalopathy in type 2 diabetes: studies in vivo and in vitro.

OBJECTIVES: The hypothalamus regulates metabolism and feeding behavior by perceiving the levels of peripheral insulin. However, little is known about the hypothalamic changes after aberrant metabolism. In this study, we investigated the changes of insulin and autophagy relevant signals of hypothalamus under diabetes mellitus. METHODS: C57B/L mice were injected with low-dose streptozotocin (STZ) and fed with high-fat diet to induce type 2 diabetes mellitus. In vitro, PC12 cells were treated with oleic acid to mimic lipotoxicity. RESULTS: Results showed that the cholesterol level in the hypothalamus of the diabetic mice was higher than that of the normal mice. The expression of insulin receptors and insulin receptor substrate-1 were downregulated and the number of Fluoro-Jade C positive cells significantly increased in the hypothalamic arcuate nucleus of the diabetic mice. Furthermore, Upregulation of mammalian target of rapamycin (mTOR) and downregulation of LC 3II were obvious in the hypothalamus of the diabetic mice. In vitro, results showed that high-lipid caused PC12 cell damage and upregulated LC3 II expression. Pretreatment of cells with 3-methyladenine evidently downregulated LC3 II expression and aggravated PC12 cell death under high lipid conditions. By contrast, pretreatment of cells with rapamycin upregulated LC3 II expression and ameliorated PC12 cell death caused by lipotoxicity. CONCLUSION: These results demonstrate that autophagy activation confers protection to neurons under aberrant metabolism and that autophagy dysfunction in the hypothalamus occurs in the chronic metabolic disorder such as T2DM.

Spermidine preconditioning ameliorates laurate-induced brain injury by maintaining mitochondrial stability.

Ischemic precondition plays a protective effect during cerebral ischemia. This effect partly depends on the autophagic activity. However, whether the activity of autophagy can exert the protective effects after cerebral ischemia is unclear. In this study, rats were treated with spermidine, an activator of autophagy, and injected with sodium laurate via the internal carotid artery to stimulate cerebral small vessel disease (CSVD). The effects of the spermidine precondition on brain injury were evaluated by behavioural test, histology assay, ultrastructure observation, and autophagic-related signals. Furthermore, the mitochondria of brain tissue were isolated, and mitDNA were extracted. The stability of mitDNA was analyzed by quantitative real-time PCR. Results showed that the penetrating artery of the striatum was damaged. This damage was accompanied by neural inflammation characterized by an increase in Fluoro-Jade C (FJC)-positive cells after sodium laurate injection. Spermidine pretreatment decreased the deletion of mitDNA and the autophagy hyperactivity induced by the laurate injection. Likewise, spermidine reduced the neurological deficit and FJC reactivation of striatum at 48 h after laurate injection. These results suggested sodium laurate injection through the internal carotid artery can induce the pathological features of CSVD characterized by the damage of penetrating artery, neurological deficit, mitochondrial impairment, and autophagic hyperactivity. Pretreatment with spermidine can ameliorate these outcomes. Further study indicated that the protective effect of the spermidine precondition is associated with the maintenance of mitochondrial stability and proper autophagy activity.