Biology subjects

Brown, C. H.

Publications and source records attributed to Brown, C. H..

3 recordsLinked to original sources

bioRxiv2026

Decoding the oxytocinergic and behavioral signatures of milk ejection

Oxytocin-mediated milk ejection (ME) is pivotal to effective breastfeeding and productive health, yet behaviorally decoding and revealing neural mechanisms of ME remains challenging. Here, we combined in vivo calcium imaging and intramammary pressure recording to uncover the temporal connections between episodic activity of oxytocin neurons and ME in conscious lactating rats. Leveraging the association and behavioral responses in dam and pup, we developed a supervised machine learning framework (ME Decoder) to enable automated analyses of ME. Inspired by its interpretable features, we defined the activity-coupled dam-pup interactions (ADPI), manifested by high kyphosis of the dam followed by pup treading and stretch, as the behavioral signatures of ME. By ME Decoder and ADPI analyses, we detected reduced ME but unaffected activity of oxytocinergic neurons after systemic blockade of oxytocin receptor. Our study uncovers the oxytocinergic and behavioral signatures of ME and provides a generalizable approach for further investigation.

neuroscience↗

bioRxiv2026

The association of extracellular vesicle (EV)-cargo miR-330-3p with postoperative delirium and a potential mechanism of tau phosphorylation and neuron toxicity

BackgroundPostoperative delirium (POD) is a frequent and severe neurocognitive complication following cardiac surgery, associated with poor long-term outcomes. The underlying mechanisms are unclear, and objective biomarkers are urgently needed. MethodsWe used pre- and post-operative plasma samples from 59 patients undergoing cardiac surgery in three separate studies with rigorous delirium assessment using the Confusion Assessment Method in a case-control design. Small extracellular vesicles (sEVs) were isolated from plasma, and their miRNA cargo was profiled using RNA sequencing. Target miRNAs were validated by qRT-PCR, and digital PCR (dPCR). The functional impact of the lead candidate miRNA was investigated in vitro by assessing tau phosphorylation and cell viability in HT22 neuronal cell line. ResultsThere were no differences in sEV morphology or numbers between patients with and without POD. While three candidate miRNAs were initially validated by qRT-PCR, subsequent dPCR analysis confirmed that only the perioperative change in plasma sEV-cargo miR-330-3p expression was significantly greater in patients who developed POD (n = 20) compared with those who did not (n = 20) (5.22 copies/L plasma; 95% Confidence Interval (CI), 1.187 to 9.256; p = 0.0139). Receiver operating characteristic curve analysis for this change yielded an area under the curve of 0.745 (95% CI, 0.589 to 0.901). In vitro overexpression of miR-330-3p in a neuronal cell line significantly increased the phosphorylation of tau at Ser199 (p < 0.0001) and Ser396 (p < 0.001) and reduced cell viability (p < 0.001). ConclusionsOur findings suggest that sEV-bound miR-330-3p increases in patients with POD after cardiac surgery. In vitro results suggest a potential pathogenic role for miR-330-3p, linking a systemic signal to tau-related neuronal injury. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIThis study identifies a specific perioperative increase in small extracellular vesicle (sEV)-cargo miR-330-3p in patients with postoperative delirium (POD) following cardiac surgery. C_LIO_LIWe provide the first evidence that miR-330-3p directly induces tau hyperphosphorylation and reduces neuronal viability in vitro, establishing a potential mechanistic link between systemic sEV signaling and neurodegeneration. C_LI What Are the Clinical Implications?O_LIThe measurement of perioperative change in miR-330-3p could serve as an objective biological marker to assist in the early identification and risk stratification of patients at high risk for POD. C_LIO_LIThe identified miR-330-3p/tau pathway represents a potential new therapeutic target; future interventions aimed at inhibiting this specific miRNA might help prevent or mitigate POD-related neuronal injury. C_LIO_LIThese findings emphasize the importance of monitoring dynamic sEV-cargo changes to better understand and manage perioperative neurocognitive disorders. C_LI

molecular biology↗

bioRxiv2021

Plasticity in intrinsic excitability of hypothalamic magnocellular neurosecretory neurons in late-pregnant and lactating rats

Oxytocin and vasopressin secretion from the posterior pituitary gland are required for normal pregnancy and lactation. Oxytocin secretion is relatively low and constant under basal conditions but becomes pulsatile during birth and lactation to stimulate episodic contraction of the uterus for delivery of the fetus and milk ejection during suckling. Vasopressin secretion is maintained in pregnancy and lactation despite reduced osmolality (the principal stimulus for vasopressin secretion) to increase water retention to cope with the cardiovascular demands of pregnancy and lactation. Oxytocin and vasopressin secretion are determined by the action potential (spike) firing of magnocellular neurosecretory neurons of the hypothalamic supraoptic and paraventricular nucleus. In addition to synaptic input activity, spike firing depends on intrinsic excitability conferred by the suite of channels expressed by the neurons. Therefore, we analysed oxytocin and vasopressin neuron activity in anaesthetised non-pregnant, late-pregnant and lactating rats to test the hypothesis that intrinsic excitability of oxytocin and vasopressin neurons is increased in late pregnancy and lactation to promote oxytocin and vasopressin secretion required for successful pregnancy and lactation. Hazard analysis of spike firing revealed a higher incidence of post-spike hyperexcitability immediately following each spike in oxytocin neurons, but not in vasopressin neurons, in late pregnancy and lactation, which is expected to facilitate high frequency firing during bursts. Despite lower osmolality in late-pregnant and lactating rats, vasopressin neuron activity was not different between non-pregnant, late-pregnant and lactating rats, and blockade of osmosensitive {Delta}N-TRPV1 channels inhibited vasopressin neurons to a similar extent in non-pregnant, late-pregnant and lactating rats. Furthermore, supraoptic nucleus {Delta}N-TRPV1 mRNA expression was not different between non-pregnant and late-pregnant rats, suggesting that enhanced activity of {Delta}N-TRPV1 channels might maintain vasopressin neuron activity to increase water retention during pregnancy and lactation.

neuroscience↗