Biology subjects

Bosch, O. J.

Publications and source records attributed to Bosch, O. J..

4 recordsLinked to original sources

bioRxiv2025

Long-term offspring loss in lactating rats: Neurobiological and emotional consequences in a novel animal model

The maternal bond is a vital social connection that supports the survival and well-being of both the caregiver and offspring. Disruption of this bond, particularly following offspring loss, can result in profound trauma with long-lasting consequences. While considerable research has focused on the impact of maternal separation on offspring development, the biological effects of offspring loss on the mother remain largely unexplored. In this study, we examined the long-term effects of offspring loss on neuroplasticity, the oxytocin (OXT) and corticotropin-releasing factor (CRF) systems, and stress-coping behaviors in Sprague-Dawley rat mothers. We examined two groups of lactating mothers: (I) a control group, in which dams remained with their pups until natural weaning, and (II) a separated group, in which all offspring were removed on lactation day 1 and the mothers experienced offspring loss until the time corresponding to weaning (19 days). Our results reveal that pup removal increased OXT receptor binding and reduced dendritic spine density in limbic brain regions, without altering estrogen receptor or calbindin cell expression. Separated mothers additionally showed elevated plasma corticosterone levels and increased passive stress-coping behaviors in the forced swim test. Remarkably, passive stress-coping behavior was rescued by central CRF receptor blockade but not by OXT treatment, indicating that the CRF system plays a central role in the distress response to offspring loss. These findings establish the rat as a novel animal model for maternal distress, provide new insights into the complex neurobiology of grief, and suggests potential directions for future studies.

neuroscience↗

bioRxiv2024

Pup defence in lactating rats: The underlying neuropeptide signalling and their interactions in the nucleus accumbens shell

Maternal aggression is a core feature of rodent maternal behaviour to defend their offspring from potential threats and is modulated by corticotropin-releasing factor (CRF) and oxytocin (OXT) systems signalling. Here, we investigated the involvement of those neuropeptide systems in maternal aggression within the nucleus accumbens shell (NAcSh), a central region of the reward and maternal circuits. Infusion of CRF or Urocortin3 (CRF-receptor 2 agonist), as well as an OXT receptor antagonist, reduced maternal aggression, suggesting a role in pup defence. Furthermore, the effects of CRF infusion in the NAcSh continued beyond the maternal defence test (MDT), reducing nursing and increasing self-grooming. Corroborating the involvement of the stress system in maternal aggression, colocalization of CRF and cFos immunoreactive cells were increased in response to the MDT, regardless of pup presence. In addition, MDT exposure increased intra-NAc OXT release in lactating rats, which could be also triggered by local retrodialysis of CRF, but not Urocortin3. However, both ligands of the CRF system elicited dopamine (DA) release in different dynamics. Crh-r1 were predominantly expressed in the medial NAc on medium-sized spiny neurons (MSN), but also in the rostral part on GABAergic interneurons. Crh-r2 were mainly expressed in the rostral NAc and its expression on GABAergic interneurons increased towards the caudal pole. Lastly, we identified CRF-enriched projections to the NAcSh descending from the prefrontal cortex, the amygdala, and the paraventricular thalamus, among others. In conclusion, intra-NAcSh dampened CRF system activity and enhanced OXT system transmission are indispensable for successful pup defence. Any perturbations like increased CRF system signalling might activate compensatory mechanisms to ensure adequate maternal behaviour.

neuroscience↗

bioRxiv2020

Chronic oxytocin-driven alternative splicing of CRFR2α induces anxiety

Recently, oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including general anxiety disorder or autism spectrum disorder. Therefore, knowledge on the involved molecular processes downstream of OXT receptor (OXTR) activation is indispensable. We reveal that alternative splicing of corticotropin releasing factor receptor 2 (CRFR2) parallels increased anxiety-like behavior following chronic OXT treatment, contrasting the well-known anxiolysis of acute OXT. In detail, chronic OXT shifts the splicing ratio between membrane-bound (mCRFR2) and soluble CRFR2 (sCRFR2) in favor of the latter via ERK1/2-MEF2A signaling. Targeted manipulations of Crfr2 splicing mimic the effect of chronic OXT, confirming its role in the regulation of anxiety-like behavior. Furthermore, chronic OXT triggers cytoplasmic distribution and extracellular release of sCRFR2 into the cerebrospinal fluid, with sCRFR2 levels positively correlating with anxiety-like behavior. Concluding, the dichotomy between anxiolytic mCRFR2 and anxiogenic sCRFR2 is the basis for the deleterious effects of chronic OXT on anxiety. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/255844v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1b50691org.highwire.dtl.DTLVardef@1c22efborg.highwire.dtl.DTLVardef@19a772eorg.highwire.dtl.DTLVardef@69af7_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2020

Concerted but segregated actions of oxytocin and vasopressin within the ventral and dorsal lateral septum determine female aggression

In contrast to males, aggression in females has been rarely studied. Here, we established a rat model of enhanced female aggression using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialyses approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), are required for female aggression. Accordingly, increased excitability of OXT-responsive neurons in the vLS and decreased excitability of AVP-responsive neurons in the dLS were essential to evoke female aggression. Finally, in vitro activation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data demonstrate that septal release of OXT and AVP affects female aggression by differential regulation of the excitatory-inhibitory balance within subnetworks of the LS.

neuroscience↗