Biology subjects

Sestan-Pesa, M.

Publications and source records attributed to Sestan-Pesa, M..

3 recordsLinked to original sources

bioRxiv2020

Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior

Microglia have been implicated in synapse remodeling by phagocytosis of synaptic elements in the adult brain. However, the underlying mechanism of such process is ill-defined. By examining microglia-neuronal interaction in the ventral hippocampus, we found a significant reduction in spine synapse number during the light phase of the light/dark cycle accompanied by increased microglial phagocytosis. This was followed by a transient rise in microglial production of reactive oxygen species (ROS) and uncoupling protein 2 (Ucp2) expression, which is a regulator of mitochondrial ROS generation. Conditional ablation of microglial Ucp2 hindered phasic elimination of spine synapses, increased accumulations of ROS and lysosome-lipid droplet complexes leading to hippocampal circuitry disruption assessed by electrophysiology, and, altered anxiety-like behavior. These observations unmasked a novel and chronotypical interaction between microglia and neurons involved in control of brain functions.

neuroscience↗

bioRxiv2020

Mitochondrial fission governed by Drp1 regulates exogenous fatty acid usage and storage

The bioenergetic function of mitochondrial fission is associated with uncoupled respiration or elimination of damaged mitochondria to maintain a healthy mitochondrial population. In the presence of a high abundance of exogenous fatty acids, cells can either store fatty acids in lipid droplets or oxidize them in mitochondria. Even though carnitine palmitoyltransferase-1 (CPT1) controls the respiratory capacity of mitochondria in fatty acid oxidation, we observed that it did not dictate the balance of storage and usage of lipids in HeLa cells. On the other hand, inhibition of mitochondrial fission by silencing dynamic-related protein 1 (DRP1) resulted in an increase in fatty acid content of lipid droplets and a decrease in fatty acid oxidation. Mitochondrial fission was not only reflective of the amount of exogenous fatty acid being processed by mitochondria, but also found to be actively involved in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.

cell biology↗

bioRxiv2020

Peri-adolescent THC Exposure Does not Lead to Anxiety-like Behavior in Adult Mice

As marijuana use during adolescence has been increasing, the need to understand the effects of its long-term use becomes crucial. Previous research suggested that marijuana consumption during adolescence increases the risk of developing mental illness, such as schizophrenia, depression, and anxiety. Ghrelin is a peptide produced primarily in the gut and is important for feeding behavior. Recent studies have shown that ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) play important roles in mediating stress, as well as anxiety and, depression-like behaviors in animal models. Here, we investigated the effects of chronic Tetrahydrocannabinol (THC) administration during adolescence (P42-55), in GHSR (GHSR-/-) knockout mice and their wild type littermates in relation to anxiety-like behaviors. We found that continuous THC exposure during peri-adolescence did not lead to any significant alterations in anxiety-like behavior of male adult mice, regardless of genotype. These data indicate that in the presence of intact GHSR signaling, THC exposure during peri-adolescence has limited if any long term impact on anxiety-like behaviors in mice.

animal behavior and cognition↗