Biology subjects

Luz, S.

Publications and source records attributed to Luz, S..

5 recordsLinked to original sources

bioRxiv2026

Maternal defense against intruders changes her subsequent maternal behavior and neural circuitry

Although female rats are typically less aggressive than male rats, lactating females will vigorously defend their nests and pups against an intruder. Much attention has been directed at the consequences of this aggression on the intruder and less on the consequences for the mother and her subsequent interactions with her pups. Here, we exposed resident Sprague-Dawley dams to the resident-intruder paradigm twice daily for five consecutive days, beginning when the dams (RES) pups were 7 days old, to assess social stress effects on maternal behavior and neurobiology. Controls were dams that had time-matched (TMC) separation from their pups but were not exposed to intruders, and naive moms which were never separated nor exposed to an intruder (CTL). We assessed the dams subsequent behavior and interactions with her pups on Day 1 and Day 5, and Fos expression after Day 5 in select regions of the prefrontal cortex, amygdala, hypothalamus and periaqueductal gray of the midbrain. In separate cohorts, after pups were weaned, the dams underwent restraint stress and plasma corticosterone assayed. PCA analysis of the dams behaviors identified three components: normal self-focused behaviors; nurturing behaviors and rough non-nurturing behaviors. Relative to CTL, RES dams exhibited more disrupted behaviors towards their pups, including, rough transport, stepping on pups, and flinging/tossing pups around the cage. In contrast, TMC Dams showed some, but fewer changes relative to CTL, suggesting that separation from pups alone does not account for all disrupted behavior in RES dams. The bulk of these behavioral effects occurred in the first 5-10 min after reunion with the pups and were seen on both the first and fifth day of testing. Of the brain regions examined, the prefrontal cortex was activated by both the defeat/intruder stress (RES) and separation stress (TMC), whereas the dorsal PAG was activated specifically by the defeat/intruder stress. The medial and basolateral amygdala exhibited differential neuronal activity between the RES defeat/intruder-exposed dams and the other two groups. The RES moms exhibited an insufficient adrenocortical response to acute restraint stress. The results suggest that amygdala-dPAG activity is important for dissociating disrupted maternal care in RES (due to defense of the nest against an intruder) from simple pup separation, both of which activate the mPFC. The experience of repeatedly defending the nest may induce subsequent disruptions in HPA responses. The amygdala-dPAG pathway may regulate aspects of stress and emotional regulation exhibited by mothers who defend their offspring against intruders.

animal behavior and cognition↗

bioRxiv2024

The glucocorticoid response element near the sphingosine-1-phopshate receptor 3 gene mitigates inflammatory processes and maladaptive behavior in females and stressed males

It is well established that glucocorticoid receptors (GRs) bind DNA, regulate gene expression, reduce inflammatory processes, and modulate behavior. However, the precise loci bound by GRs that are necessary for these effects are not fully understood. Here, we deleted the GR binding site near the sphingosine-1-phospate receptor 3 gene using a CRISPR/Cas9 approach (S1PR3GR-/GR- rats). Defeated S1PR3GR-/GR- males displayed increased inflammatory markers and social anxiety-like behavior. Similar effects were observed in non-stressed females, indicating a greater dependence for GR-induced S1PR3 in females. Coherent neural activity between the locus coeruleus (LC) and medial prefrontal cortex (mPFC) was increased in S1PR3GR-/GR- males following 7 defeats. Chemogenetically inhibiting mPFC-projecting LC neurons during defeat increased subsequent social interaction in wild-type and S1PR3GR-/GR- males. Together, these findings demonstrate that GR-induced S1PR3 promotes resilience by mitigating stress-induced inflammatory processes and LC-mPFC coherence. One Sentence SummaryGlucocorticoid receptor-induced expression of sphingosine-1- phosphate receptor 3 reduces social anxiety-like behavior by mitigating stress-induced inflammatory processes and coherent neural activity between the locus coeruleus and medial prefrontal cortex.

neuroscience↗

bioRxiv2022

BioNE: Integration of network embeddings for supervised learning

A network embedding approach reduces the analysis complexity of large biological networks by converting them to lowdimensional vector representations (features/embeddings). These lower-dimensional vectors can then be used in machine learning prediction tasks with a wide range of applications in computational biology and bioinformatics. Several network embedding approaches have been proposed with different methods of generating vector representations. These network embedding approaches can be quite diverse in terms of data representation and implementation. Moreover, most were not originally developed for biological networks. Therefore comparing and assessing the performance of these diverse models in practice, in biological contexts, can be challenging. To facilitate such comparisons, we have developed the BioNE framework for integration of different embedding methods in prediction tasks. Using this framework one can easily assess, for instance, whether combined vector representations from multiple embedding methods offer complementary information with regards to the network features and thus better performance on prediction tasks. In this paper, we present the BioNE software suite for embedding integration, which applies network embedding methods following standardised network preparation steps, and integrates the vector representations achieved by these methods using three different techniques. BioNE enables selection of prediction models, oversampling methods, feature selection methods, cross-validation type and cross-validation parameters. Availability and implementationBioNE pipeline and detailed explanation of implementation is freely available on GitHub, at https://github.com/pooryaparvizi/BioNE

bioinformatics↗

bioRxiv2021

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)-mediated plasticity in the paraventricular thalamic nucleus promotes a fundamental adaptation to stress

BACKGROUNDHabituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of post-traumatic stress disorder (PTSD). In rodents, habituation is observed in neural, neuroendocrine and behavioral responses to repeated exposure to the predictable and moderately intense stress or restraint. We previously demonstrated that lesions to the posterior division of the paraventricular thalamic nucleus (pPVT) impairs habituation. However, the underlying molecular mechanisms and specific neural connections among the pPVT and other brain regions that underlie habituation are unknown. METHODSBehavioral and neuroendocrine habituation was assessed in adult male Sprague-Dawley restraints using the repeated restraint paradigm. Pan neuronal and Cre-dependent Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were used to chemogenetically inhibit the pPVT and the subpopulation of pPVT neurons that project to the medial prefrontal cortex (mPFC), respectively. Activity-regulated cytoskeleton-associated protein (Arc) expression was knocked down in the pPVT using siRNA directed towards Arc. Golgi staining was used to assess structural plasticity of pPVT neurons. Local field potential recordings were used to assess coherent neural activity between the pPVT and mPFC. The attentional set-shifting task was used to assess mPFC-dependent behavior. RESULTSHere, we show that Arc promotes habituation by increasing stress-induced spinogenesis in the pPVT, increasing coherent neural activity with the mPFC, and improving mPFC-mediated cognitive flexibility. CONCLUSIONOur results demonstrate that Arc induction in the pPVT regulates habituation to repeated restraint and mPFC function. One Sentence SummaryWe demonstrate that Arc in the posterior division of the paraventricular thalamic nucleus promotes habituation to repeated stress by increasing dendritic spines.

neuroscience↗

bioRxiv2021

FTY720 (Fingolimod), a modulator of sphingosine-1-phosphate receptors, increases baseline hypothalamic-pituitary adrenal axis activity and alters behaviors relevant to affect and anxiety

FTY720 (fingolimod) is an analog of sphingosine, a ubiquitous sphingolipid. Phosphorylated FTY720 (FTY720-P) non-selectively binds to sphingosine-1-phosphate receptors (S1PRs) and regulates multiple cellular processes including cell proliferation, inflammation, and angiogenesis. We recently demonstrated that S1PR3 expression in the medial prefrontal cortex (mPFC) of rats promotes stress resilience and that S1PR3 expression in blood may serve as a biomarker for PTSD. Here we investigate the effects of FTY720 in regulating the stress response. We found that single and repeated intraperitoneal injections of FTY720 increased baseline plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations. FTY720 also mitigated restraint-induced increases in ACTH and corticosterone. FTY720 reduced social anxiety- and despair-like behavior as assessed by increased social interaction time and reduced time spent immobile in the Porsolt forced swim test. In blood, FTY720 administration reduced lymphocyte and reticulocyte counts, but raised erythrocyte counts. FTY720 also reduced mRNA of angiopoietin 1, endothelin 1, plasminogen 1, Vegf-B, and Mmp2 in the medial prefrontal cortex, suggesting that FTY720 reduced angiogenesis. The antidepressant-like and anxiolytic-like effects of FTY720 may be attributed to reduced angiogenesis as increased stress-induced blood vessel density in the brain contributes to depression- and anxiety-like behavior in rats. Together, these results suggest that S1PRs regulate baseline HPA axis activity but reduces social anxiety and despair providing further evidence that S1PRs are important and novel regulators of stress-related functions.

neuroscience↗