Biology subjects

Vizcarra, V. S.

Publications and source records attributed to Vizcarra, V. S..

2 recordsLinked to original sources

bioRxiv2024

Spinal Cord Injury Enhances Lung Inflammation and Exacerbates Immune Response After Acute Lung Injury

The severity of spinal cord injury (SCI) is closely tied to pulmonary function, especially in cases of higher SCI levels. Despite this connection, the underlying pathological mechanisms in the lungs post-SCI are not well understood. Previous research has established a connection between disrupted sympathetic regulation and splenocyte apoptosis in high thoracic SCI, leading to pulmonary dysfunction. The aim of this study was to investigate whether mice with low-level SCI exhibit increased susceptibility to acute lung injury by eliciting systemic inflammatory responses that operate independently of the sympathetic nervous system. Here, we employed T9 contusion SCI and exposed mice to aerosolized lipopolysaccharide (LPS) to simulate lung inflammation associated with acute respiratory distress syndrome (ARDS). Twenty-four hours post-LPS exposure, lung tissues and bronchoalveolar lavage (BAL) fluid were analyzed. LPS markedly induced proinflammatory gene expression (SAA3, IRG1, NLRP3, IL-1beta, MCP-1) and cytokine release (IL-1beta, IL-6, MCP-1) in SCI mice compared to controls, indicating an exaggerated inflammatory response. Infiltration of Ly6G/C positive neutrophils and macrophages was significantly higher in SCI mice lungs post-LPS exposure. Interestingly, spleen size and weight did not differ between control and SCI mice, suggesting that T9 SCI alone does not cause spleen atrophy. Notably, bone-marrow-derived macrophages (BMDMs) from SCI mice exhibited hyper-responsiveness to LPS. This study demonstrated an increase in lung inflammation and immune responses subsequent to low-level T9 SCI, underscoring the widespread influence of systemic inflammation post-SCI, especially pronounced in specific organs like the lungs. KEY POINTSO_LISpinal cord injury leads to increased lung permeability following LPS inhalation. C_LIO_LISpinal cord injury amplifies cytokine release after exposure to LPS. C_LIO_LISpinal cord injury affects bone marrow-derived macrophages, showing heightened glycolytic activity and inflammatory conditions. C_LI

immunology↗

bioRxiv2023

The Role of Ryanodine Receptor 2 in Drug-Associated Learning

Type-2 ryanodine receptor (RyR2) ion channels facilitate the release of Ca2+ from stores and serve an important function in neuroplasticity. The role for RyR2 in hippocampal-dependent learning and memory is well established and chronic hyperphosphorylation of RyR2 (RyR2P) is associated with pathological calcium leakage and cognitive disorders, including Alzheimers disease. By comparison, little is known about the role of RyR2 in the ventral medial prefrontal cortex (vmPFC) circuitry important for working memory, decision making, and reward seeking. Here, we evaluated the basal expression and localization of RyR2 and RyR2P in the vmPFC. Next, we employed an operant model of sucrose, cocaine, or morphine self-administration (SA) followed by a (reward-free) recall test, to reengage vmPFC neurons and reactivate reward-seeking and re-evaluated the expression and localization of RyR2 and RyR2P in vmPFC. Under basal conditions, RyR2 was expressed in pyramidal cells but not regularly detected in PV/SST interneurons. On the contrary, RyR2P was rarely observed in PFC somata and was restricted to a different subcompartment of the same neuron - the apical dendrites of layer-5 pyramidal cells. Chronic SA of drug (cocaine or morphine) and nondrug (sucrose) rewards produced comparable increases in RyR2 protein expression. However, recalling either drug reward impaired the usual localization of RyR2P in dendrites and markedly increased its expression in somata immunoreactive for Fos, a marker of highly activated neurons. These effects could not be explained by chronic stress or drug withdrawal and instead appeared to require a recall experience associated with prior drug SA. In addition to showing the differential distribution of RyR2/RyR2P and affirming the general role of vmPFC in reward learning, this study provides information on the propensity of addictive drugs to redistribute RyR2P ion channels in a neuronal population engaged in drug-seeking. Hence, focusing on the early impact of addictive drugs on RyR2 function may serve as a promising approach to finding a treatment for substance use disorders.

neuroscience↗