Biology subjects

Raina, S.

Publications and source records attributed to Raina, S..

5 recordsLinked to original sources

bioRxiv2024

Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes

Astrocytes are increasingly thought to have underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs and govern dopamine release via nicotinic acetylcholine receptors on subsecond timescales. We identify that ChI somata are in unexpectedly close proximity to astrocyte somata, in mouse and human, forming a "soma-to-soma" satellite-like configuration not typically observed for other striatal neurons. Transient depolarization of astrocytes in mouse striatum reversibly regulated ChI excitability by decreasing extracellular calcium. These findings reveal a privileged satellite astrocyte-interneuron interaction for striatal ChIs operating on subsecond timescales via regulation of extracellular calcium dynamics to shape downstream striatal circuit activity and dopamine signaling.

neuroscience↗

bioRxiv2024

Centriolar satellites are sites of translation of centrosomal and ciliary proteins

Centriolar satellites are cytoplasmic particles found in the vicinity of centrosomes and cilia whose functional contribution to the formation of these cellular structures has long been unclear. By characterizing the main scaffolding component of satellites, PCM1 or Combover in Drosophila, we show that satellites are not involved in cellular trafficking as previously thought but rather act as sites for the coordinate translation of centrosomal and ciliary proteins through the interaction with a set of RNA binding proteins and proteins involved in quality control. Strikingly, the concentration of satellites near centrosomes and cilia in vertebrates is not a conserved feature and therefore dispensable for satellite function. Such coordinate synthesis may be a general feature in eukaryotic cells to facilitate protein complex formation and cellular compartmentalization. One-Sentence SummaryCentriolar satellites facilitate the coordinate synthesis of centrosomal and ciliary proteins.

cell biology↗

bioRxiv2023

CCR3 inhibition suppresses inflammation-driven recruitment of peripheral immune cells to the eye

C-C chemokine receptor type 3 (CCR3) has been linked with age-related macular degeneration (AMD) pathologies. Specifically, its function as an immune modulator in AMD remains unclear. To address this question, we investigated the impact of CCR3 inhibition on inflammation, a key driver of AMD pathologies, by assessing inflammatory cytokines and infiltrating immune cells in two models of ocular inflammation. Mice were orally dosed twice a day with AKST4290, a CCR3 small molecular inhibitor, in the sodium iodate (NaIO3) and myelin oligodendrocyte glycoprotein (MOG) models. A combination of autoradiography and analytical chemistry techniques were used to assess drug concentration and distribution. Bead-based multiplexing technology was used to determine cytokine concentrations, and flow cytometry and immunohistochemistry was used to ascertain ocular immune-cell composition. CCR3 expression was detected in the retinal pigment epithelium (RPE)/choroid complex where AKST4290 was found to preferentially accumulate at sustained levels. In the NaIO3 model, inhibition of CCR3 with AKST4290 significantly decreased both the concentration of specific chemokines and the number of multiple populations of infiltrating peripheral immune cell. Furthermore, effects of CCR3 inhibition on immune cell infiltration were confirmed in the MOG model. These data demonstrate that CCR3 inhibition strongly modulates local inflammation by impacting both cytokine concentrations and immune cell composition in ocular diseases. Moreover, these findings together with the known role of CCR3 in promoting pathologic angiogenesis implicate a pleiotropic role for CCR3 in AMD.

cell biology↗

bioRxiv2023

Juvenile and adult expression of polyglutamine expanded huntingtin produce distinct aggregate distributions in Drosophila muscle

While Huntingtons disease (HD) is widely recognized as a disease affecting the nervous system, much evidence has accumulated to suggest peripheral or non-neuronal tissues are affected as well. Here, we utilize the UAS/GAL4 system to express a pathogenic HD construct in the muscle of the fly, and characterize the effects. We observe detrimental phenotypes such as reduced lifespan, decreased locomotion, and accumulation of protein aggregates. Strikingly, depending on the GAL4 driver used to express the construct we saw different aggregate distributions and severity of phenotypes. These different aggregate distributions were found to be dependent on expression level and the timing of expression. Hsp70, a well-documented suppressor of polyglutamine aggregates, was found to strongly reduce the accumulation of aggregates in the eye, but in the muscle it did not prevent the reduction of the lifespan. Therefore, the molecular mechanisms underlying the detrimental effects of aggregates in the muscle are distinct from the nervous system.

genetics↗

bioRxiv2020

Versatile Method to measure locomotion

Many studies require the ability to quantify locomotor behavior over time. The list of tracking softwares and their capabilities are constantly growing. At the 2019 CanFly Conference we presented preliminary results from an investigation of the effects of expressing polyglutamine repeats in fly muscles on longevity, locomotion and protein aggregation and received a lot of inquiries about our protocol to measure locomotion and how to use the FlyTracker MatLab software. This report describes a versatile locomotion measuring device and custom MatLab scripts for the extraction and analysis, and compilation of FlyTracker data in a format compatible with spreadsheet softwares. The measurement and analysis of multiple genotypes and both sexes across age shows that this method yields reproducible results that confirm that normal aging is associated with a progressive decline in locomotion as indicated by increased immobility and reduced velocity.

animal behavior and cognition↗