Adolescent-like Processing of Behaviorally Salient Cues in Sensory and Prefrontal Cortices of Adult Preterm-Born Mice DOI Creative Commons
Adema Ribic,

Emily McCoy,

Vyshnavi Pendala

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Preterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it unclear how prematurity impacts circuits that support these functions. To address this, we trained adult mice born day early (preterm mice) on visual discrimination task found they commit more errors fail to achieve high levels of performance. Using in vivo electrophysiology, the neurons primary cortex (V1) V1-projecting prefrontal anterior cingulate (ACC) are hyper-responsive reward, reminiscent cue processing adolescence. Moreover, non-rewarded fails robustly activate V1 ACC during error trials, contrast fast-spiking (FS) interneurons which show elevated error-related activity, suggesting preterm impairs function monitoring. Finally, environmental enrichment, well-established paradigm promotes maturation, failed improve performance mice, limited capacity interventions reducing deficits after birth. Altogether, our study first time identifies potential circuit mechanisms population highlights vulnerability advanced onset extrauterine experience.

Language: Английский

Protection from oxygen–glucose deprivation by neurosteroid treatment in primary neurons and oligodendrocytes DOI Creative Commons
Roisin A. Moloney,

Carlton L. Pavy,

Richard G. S. Kahl

et al.

In Vitro Cellular & Developmental Biology - Animal, Journal Year: 2024, Volume and Issue: 60(9), P. 1068 - 1084

Published: July 29, 2024

Abstract Preterm birth results in an increased risk of neonatal brain injury and neurobehavioural disorders. Despite the seriousness these adverse outcomes, there are currently no effective therapies to protect vulnerable developing brain. We propose that neurosteroid replacement therapy may be a novel approach reducing detrimental neurological outcomes following preterm birth. The use guinea pig primary neuronal oligodendrocyte cultures with relevance late gestation allows insight into mechanisms behind effectiveness treatments. Primary were derived from fetal frontal cortex tissue at gestational age 62 (GA62). Cell pre-treated either etifoxine (5 µM) or zuranolone (1 µm) for 24 h prior insult. Cells then exposed oxygen–glucose deprivation (OGD; 0% O 2 glucose DMEM; insult) sham (standard cell culture conditions; 25 mM DMEM) h. Lactate dehydrogenase assay (LDH) was performed OGD as measure cytotoxicity. Relative mRNA expression key markers, well receptors transporters, quantified using high throughput (Fluidigm) RT-PCR. significantly cellular cytotoxicity both neurons oligodendrocytes. Additionally, marker reduced OGD, oligodendrocytes displayed arrested markers lineage progression. Treatment restored number parameters back control levels, whereas treatment provided robust improvement all examined. This study has demonstrated neuroprotective potential model hypoxia related Neuroprotection appears mediated through glutamate reduction neurotrophic factor (BDNF). Future work is warranted examining treatments vivo, overall aim suppress associated damage reduce long term affected offspring.

Language: Английский

Citations

2
Zuranolone therapy protects frontal cortex neurodevelopment and improves behavioral outcomes after preterm birth DOI Creative Commons
Roisin A. Moloney, Hannah K. Palliser,

Carlton L. Pavy

et al.

Brain and Behavior, Journal Year: 2024, Volume and Issue: 14(9)

Published: Sept. 1, 2024

Abstract Background Preterm birth is associated with brain injury and long‐term behavioral abnormalities, for which there are limited prevention options. When born preterm, infants prematurely lose placental neurosteroid (allopregnanolone) support. This increases the risk of excitotoxic damage to brain, injury, causing deficits in behavior, myelination, alterations neurotransmitter pathways. We propose that postnatal restoration action through zuranolone therapy will reduce neurological impairments following preterm birth. Methods: Guinea pig dams underwent survival cesarean section surgery deliver pups (GA64) or at term (GA69). Between equivalence age, received vehicle (15% β‐cyclodextrin) allopregnanolone analogue (1 mg/kg/day). Behavioral analysis was performed day (PND) 7 40, before tissue collection PND 42. Immunostaining myelin basic protein (MBP), as well real‐time polymerase chain reaction characterize oligodendrocyte lineage pathways, frontal cortex tissues. Results: Zuranolone treatment prevented hyperactive phenotype preterm‐born offspring, most markedly males. Additionally, preterm‐related reductions MBP were ameliorated. Several mRNA expression dopaminergic, glutamatergic, GABAergic pathways also restored back a control level. Conclusion: first study assess neuroprotective improved outcomes structural changes continued long until least late childhood timepoint. Clinical studies warranted further exploring possibilities this

Language: Английский

Citations

2
Adolescent-like Processing of Behaviorally Salient Cues in Sensory and Prefrontal Cortices of Adult Preterm-Born Mice DOI Creative Commons

Emily McCoy,

Vyshnavi Pendala,

Mona Fariborzi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract Preterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it unclear how prematurity impacts circuits that support these functions. To address this, we trained adult mice born day early (preterm mice) on visual discrimination task found they commit more errors fail to achieve high levels of performance. Using vivo electrophysiology , the neurons primary cortex (V1) V1-projecting prefrontal anterior cingulate (ACC) are hyper-responsive reward, reminiscent cue processing adolescence. Moreover, non-rewarded fails robustly activate V1 ACC during error trials, contrast fast-spiking (FS) interneurons which show elevated error-related activity, suggesting preterm impairs function monitoring. Finally, environmental enrichment, well-established paradigm promotes maturation, failed improve performance mice, limited capacity interventions reducing deficits after birth. Altogether, our study first time identifies potential circuit mechanisms population highlights vulnerability advanced onset extrauterine experience.

Language: Английский

Citations

0
Neurosteroid replacement approaches for improving outcomes after compromised pregnancies and preterm birth DOI Creative Commons
Jonathan J. Hirst, Hannah K. Palliser,

Carlton L. Pavy

et al.

Frontiers in Neuroendocrinology, Journal Year: 2024, Volume and Issue: unknown, P. 101169 - 101169

Published: Nov. 1, 2024

Language: Английский

Citations

0
Adolescent-like Processing of Behaviorally Salient Cues in Sensory and Prefrontal Cortices of Adult Preterm-Born Mice DOI Creative Commons
Adema Ribic,

Emily McCoy,

Vyshnavi Pendala

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Preterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it unclear how prematurity impacts circuits that support these functions. To address this, we trained adult mice born day early (preterm mice) on visual discrimination task found they commit more errors fail to achieve high levels of performance. Using in vivo electrophysiology, the neurons primary cortex (V1) V1-projecting prefrontal anterior cingulate (ACC) are hyper-responsive reward, reminiscent cue processing adolescence. Moreover, non-rewarded fails robustly activate V1 ACC during error trials, contrast fast-spiking (FS) interneurons which show elevated error-related activity, suggesting preterm impairs function monitoring. Finally, environmental enrichment, well-established paradigm promotes maturation, failed improve performance mice, limited capacity interventions reducing deficits after birth. Altogether, our study first time identifies potential circuit mechanisms population highlights vulnerability advanced onset extrauterine experience.

Language: Английский

Citations

0