Biology subjects

Kalita, K.

Publications and source records attributed to Kalita, K..

5 recordsLinked to original sources

bioRxiv2026

The effect of preproenkephalin gene deletion on heart function in mice

Enkephalins, the endogenous ligands of the - and {delta}-opioid receptors, are abundantly expressed in the nervous system and peripheral organs, including the heart. Accumulating evidence suggests that they participate in cardiac development and act as autocrine and paracrine modulators of heart activity. Here, we investigate the role of enkephalins in cardiac physiology using a newly generated mouse strain with a complete ablation of the preproenkephalin (Penk) gene. We find that, although adult mutant mice weighed less, the mutation caused no apparent changes in behavioral phenotype, no increase in anxiety-like behaviors, and only a mild reduction in locomotor activity. There was no effect of Penk deletion on heart weight or size. A comprehensive analysis of left ventricular function using MRI revealed normal basal cardiac performance, except for a significant reduction in the peak fill and ejection rates. There were no significant effects of Penk deletion on left ventricular function after {beta}1-adrenergic stimulation with dobutamine. At the same time, we observed the expected significant differences in heart size and function between male and female mice. In conclusion, our data show that enkephalins are not essential for normal heart development and have a moderate impact on adult heart function under basal conditions.

neuroscience↗

bioRxiv2025

Lcn2 deficiency leads to social impairments independent of maternal immune activation.

Maternal infection during pregnancy is a well-established risk factor for neurodevelopmental disorders (NDDs), yet the underlying molecular mechanisms remain poorly understood. Lipocalin-2 (Lcn2), an innate immune protein that is highly upregulated during infection, also affects neuronal and glial function. This study investigates the role of Lcn2 in shaping brain development, particularly after maternal immune activation (MIA). To mimic maternal infection, pregnant mice received intraperitoneal injections of either lipopolysaccharide (LPS) or saline on embryonic days 16 to 18 to model infection during the second trimester of pregnancy in humans. We first showed that Lcn2 mRNA is expressed in the fetal brain and that MIA significantly upregulates Lcn2 mRNA and protein in the hippocampus and neocortex of both sexes. To assess functional relevance, we employed Lcn2 heterozygous females to generate wild-type and Lcn2 KO offspring from the MIA and control groups. Both female and male offspring underwent a battery of behavioral assays. Lcn2 deletion and MIA independently induced deficits in social behavior and increased repetitive behavior phenotypes relevant to NDDs in adult animals. However, their combination did not exacerbate these effects, suggesting an occlusion effect. Interestingly, no deficits were observed in the learning and memory task. To investigate potential shared molecular mechanisms, we performed RNA sequencing of the fetal forebrain 4 hours after the final LPS injection. This analysis revealed an overlapping group of differentially expressed genes in the Lcn2 KO and MIA groups, indicating convergence on similar transcriptional pathways that may underlie the observed behavioral phenotypes. These results suggest that while Lcn2 may not mediate the pathological effects of prenatal immune challenge, it plays a critical role in normal brain development.

neuroscience↗

bioRxiv2025

Temporal and protein-specific S-palmitoylation supports synaptic and neural network plasticity

S-palmitoylation, a dynamic post-translational modification, has long been suggested to play a pivotal role in synaptic plasticity, learning, and memory. However, its precise impact on synaptic proteins and function remains unclear. In this study, we show that acute protein depalmitoylation in the hippocampus differentially affects short- and long-term synaptic plasticity, depending on synapse type. Strikingly, depalmitoylation also reprograms neuronal spiking timing following associative network activation. Our research identifies pre- and postsynaptic proteins dynamically regulated by S-palmitoylation during synaptic plasticity and suggests this modification occurs in isolated excitatory synapses. We also demonstrate that S-palmitoylation targets specific proteins within minutes and is not proteome-wide. These findings mark a significant advance in understanding how lipid modifications drive neural adaptability, memory, and learning.

neuroscience↗

bioRxiv2023

Matrix Metalloproteinase-9 controls structural synaptic plasticity via BDNF-dependent signaling

Synaptic plasticity underlies learning and memory processes as well as contributes, in its aberrant form, to neuropsychiatric disorders. One of its major forms is structural long-term potentiation (sLTP), an activity-dependent growth of dendritic spines that harbor excitatory synapses. The process depends on the release of brain-derived neurotrophic factor (BDNF), and activation of its receptor, TrkB. Matrix metalloproteinase-9 (MMP-9), an extracellular protease is essential for many forms of neuronal plasticity engaged in physiological as well as pathological processes. Here, we utilized two-photon microscopy and two-photon glutamate uncaging to demonstrate that MMP-9 activity is essential for sLTP and is rapidly ([~]seconds) released from dendritic spines in response to synaptic stimulation. Moreover, we show that either chemical or genetic inhibition of MMP-9 impairs TrkB activation, as measured by fluorescence lifetime imaging microscopy of FRET sensor. Furthermore, we provide evidence for a cell-free cleavage of proBDNF into mature BDNF by MMP-9. Our findings point to the autocrine mechanism of action of MMP-9 through BDNF maturation and TrkB activation during sLTP.

neuroscience↗

bioRxiv2020

Serum response factor is essential for synaptic maturation in the hippocampus

Disturbances of gene expression patterns that occur during brain development can severely affect signal transmission, connectivity, and plasticity--key features that underlie memory formation and storage in neurons. Abnormalities at the molecular level can manifest as changes in the structural and functional plasticity of dendritic spines that harbor excitatory synapses. This can lead to such developmental neuropsychiatric conditions as Autism spectrum disorders, intellectual disabilities, and schizophrenia. The present study investigated the role of the major transcriptional regulator serum response factor (SRF) in synapse maturation and its impact on behavioral phenotypes. Using in vitro and in vivo models of early postnatal SRF deletion, we studied its influence on key morphological and physiological hallmarks of spine development. The elimination of SRF in developing neurons resulted in a phenotype of immature dendritic spines and impairments in excitatory transmission. Moreover, using a combination of molecular and imaging techniques, we showed that SRF-depleted neurons exhibited a lower level of specific glutamate receptor mRNAs and a decrease in their surface expression. Additionally, the early postnatal elimination of SRF in hippocampal CA1 excitatory neurons caused spine immaturity and a specific social deficit that is frequently observed in autism patients. Altogether, our data suggest that the regulation of structural and functional dendritic spine maturation begins at the stage of gene transcription, which underpins the crucial role of such transcription factors as SRF. Moreover, disturbances of the postnatal expression of SRF translate to behavioral changes in adult animals.

neuroscience↗