Neuronal apoptosis drives remodeling states of microglia and shifts in survival pathway dependence

Microglia serve critical remodeling roles that shape the developing nervous system, responding to the changing neural environment with phagocytosis or soluble factor secretion. Recent single-cell sequencing (scRNAseq) studies have revealed the context-dependent diversity in microglial properties and gene expression, but the cues promoting this diversity are not well defined. Here, we ask how interactions with apoptotic neurons shape microglial state, including lysosomal and lipid metabolism gene expression and independence from Colony-stimulating factor 1 receptor (CSF1R) for survival. Using early postnatal mouse retina, a CNS region undergoing significant developmental remodeling, we performed scRNAseq on microglia from mice that are wild-type, lack neuronal apoptosis (Bax KO), or are treated with CSF1R inhibitor (PLX3397). We find that interactions with apoptotic neurons drives multiple microglial remodeling states, subsets of which are resistant to CSF1R inhibition. We find that TAM receptor Mer and complement receptor 3 are required for clearance of apoptotic neurons, but that Mer does not drive expression of remodeling genes. We show TAM receptor Axl is negligible for phagocytosis or remodeling gene expression but is consequential for microglial survival in the absence of CSF1R signaling. Thus, interactions with apoptotic neurons shift microglia towards distinct remodeling states and through Axl, alters microglial dependence on survival pathway, CSF1R.

EXPRESSÃO GÊNICA DO METABOLISMO LIPÍDICO DA CHIA SOB DOSES DE FÓSFORO

A chia (Salvia hispanica L.) é uma planta anual herbácea considerada como fonte natural de ácidos graxos ômega-3, fibras, proteínas e antioxidantes. No entanto o cultivo no Brasil ainda é recente e as informações e recomendações técnicas existentes são limitadas, principalmente a respeito de adubação e época de semeadura. Portanto, o presente trabalho objetivou avaliar o efeito da aplicação de doses de fósforo na expressão de genes responsáveis pela síntese de lipídios da cultura da chia. Foi conduzido o experimento em na Fazenda de Universidade Estadual de Maringá no Campus Regional de Umuarama. O solo usado no experimento é um Latossolo Vermelho Distrófico típico, com textura arenosa. O delineamento experimental utilizado foi o inteiramente casualizado com quatro e cinco repetições. Os tratamentos foram compostos por quatro doses de P2O5 aplicados na semeadura (0, 40, 80 e 120 kg ha-1). Foi avaliada a expressão dos genes responsáveis pelo metabolismo de lipídios OLE1 e MGAT. Palavras-chave: Salvia hispânica; teor de óleo; adubação fosfatada. Lipid metabolism gene expression of chia under phosphorus rates ABSTRACT: Chia (Salvia hispanica L.) is an annual herbaceous plant considered as a natural omega-3 fatty acids, fibers, proteins and antioxidants source. However, cultivation in Brazil is still recent and the existing information and technical recommendations are limited, mainly regarding fertilization. Therefore, the present work aimed the phosphorus rates application effect on the genes expression responsible for chia plants lipid synthesis. The experiment was conducted at farm of Universidade Estadual de Maringá at the Regional Campus of Umuarama, Paraná, Brazil. The experimental design was a completely randomized design with four and five replications. The treatments were composed of four rates of P2O5 at sowing (0, 40, 80 and 120 kg ha-1). The expression of the genes responsible for lipid metabolism OLE1 and MGAT. Key words: Salvia hispanica; oil meaning; phosphate fertilization.

Lipid Metabolism Gene Expression And Cellularity of Intramuscular Adipocytes Within The Longissimus Muscle of Angus- And Wagyu-Sired Cattle When Raised To A Similar Age or Body Weight

Background: This study investigates intramuscular (IM) adipocyte development and growth in the Longissimus muscle (LM) between Wagyu- and Angus-sired steers compared at a similar age and days on feed (DOF) endpoint or similar body weight (BW) endpoint by measuring IM adipocyte cell area and lipid metabolism gene expression. Methods: Angus-sired steers (AN, n=6) were compared with steers from two different Wagyu sires, selected for either growth or marbling, to be compared at a similar DOF (WA-GD, n=5 and WA-MD, n=5) in experiment 1 or BW (WA-GB, n=4 and WA-MB, n=5) in experiment 2, respectively. Results: In experiment 1, WA-MD steers had a greater percentage of IM fat in the LM compared with AN and WA-GD steers. In experiment 2, WA-MB steers had a greater percentage of IM fat in the LM compared with AN and WA-GB steers. The distribution of IM adipocyte area was unimodal at all biopsy collections, with IM adipocyte area becoming progressively larger as cattle age and BW increased (P≤0.01). Peroxisome proliferator activated receptor delta (PPARd) was upregulated earlier for WA-MD and WA-MB cattle compared with other steers at a similar age and BW (P≤0.02; treatment×biopsy interaction). An earlier upregulation of PPARd is believed to have then upregulated peroxisome proliferator activated receptor gamma (PPARg) at a lesser BW for WA-MB steers (P=0.09; treatment×biopsy interaction), while WA-MD steers had a greater (P≤0.04) overall mean PPARg expression compared with other steers. Glycerol-3-phosphate acyltransferase, lipin 1, and hormone sensitive lipase demonstrated expression patterns similar to PPARg and PPARd or CCAAT enhancer binding protein beta, which emphasizes their importance in marbling development and growth. Additionally, WA-MD and WA-MB steers often had a greater early expression of fatty acid transporters (fatty acid transport protein 1; P<0.02; treatment×biopsy interaction) and binding proteins (fatty acid binding protein 4) compared with other steers. With many lipolytic genes upregulated at harvest, acetyl-CoA carboxylase beta may be inhibiting fatty acid oxidation in the LM to allow greater IM fat accumulation.Conclusions: Cattle with a greater marbling propensity appear to upregulate adipogenesis at a lesser maturity through PPARd, PPARg, and possibly adipogenic regulating compounds in lysophosphatidic acid and diacylglycerol.