The effects of early life stress on the excitatory/inhibitory balance of the medial prefrontal cortex

Ohta, Kenichi; Suzuki, Shingo; Warita, Katsuhiko; Sumitani, Kazunori; Tenkumo, Chiaki; Ozawa, Toshifumi; Ujihara, Hidetoshi; Kusaka, Takashi; Miki, Takanori

doi:10.1016/j.bbr.2019.112306

Cited by 41 publications

(52 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, lesions in the mediodorsal thalamus at PD 4 causes a reduction in the number of dendrites and in synaptic density in the prefrontal cortex [40]. Together, these results suggest that repeated MS impedes BDNF expression in the mPFC during the critical period for primary dendritic and synaptic development, and that these influences persist through subsequent brain development, possibly resulting in a decrease in synaptic density followed by abnormality of mPFC-dependent behaviors such as those that have been reported in previous studies [10,40,41,42].…”

Section: Discussionsupporting

confidence: 75%

“…Our previous study showed that MS transiently reduced the expression of BDNF in the hippocampus during early development but not in juveniles [18]. Likewise, MS is likely to affect BDNF expression in the mPFC, which might cause a reduction in inhibitory function followed by E/I imbalances related to social recognition deficits reported in our previous study [10]. However, many earlier studies have focused on the observation that MS affects BDNF expression in the mPFC during adolescence to adulthood, while there are only a few reports about the influences of MS on BDNF during early brain development.…”

Section: Introductionmentioning

confidence: 60%

“…In each dam, half the male pups were assigned to the MS group, and the other half of the male pups were assigned to the mother-reared control (MRC) group to remove differences caused by maternal care. The MS procedure has been described previously [10,18,19]. In brief, in the MS group, the pups were separated from their dams for 3 h, twice a day (from 0900 to 1200 and from 1300 to 1600) between PD 2 and PD 20.…”

Section: Animals and Maternal Separation Proceduresmentioning

confidence: 99%

“…The mPFC was acquired as previously described [10]. Briefly, pups from both groups were anesthetized with isoflurane and intracardially perfused with medical-grade physiologic saline at PDs 4, 7, 10, 14, and 21.…”

Section: Tissue Sampling For Real-time Rt-pcr and Western Blotmentioning

confidence: 99%

“…One of these abnormalities is social deficit, which can be triggered by stressful environments [7,8,9]. Our recent study with rats revealed that MS during preweaning caused social deficits related to social recognition after maturation [10]. In addition, MS decreases the number of inhibitory neurons and synapses, and causes an excitatory and inhibitory (E/I) imbalance in the medial prefrontal cortex (mPFC), which is partly involved in the pathology of social recognition deficits [10].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development

Tenkumo

Ohta

Suzuki

et al. 2020

Heliyon

Self Cite

View full text Add to dashboard Cite

It is widely accepted that maternal separation (MS) induces stress in children and disrupts neural circuit formation during early brain development. Even though such disruption occurs transiently early in life, its influence persists after maturation, and could lead to various neurodevelopmental disorders. Our recent study revealed that repeated MS reduces the number of inhibitory neurons and synapses in the medial prefrontal cortex (mPFC) and causes mPFC-related social deficits after maturation. However, how MS impedes mPFC development during early brain development remains poorly understood. Here, we focused on brain-derived neurotrophic factor (BDNF) involved in the development of inhibitory neurons, and examined time-dependent BDNF expression in the mPFC during the pre-weaning period in male rats exposed to MS. Our results show that MS attenuates BDNF expression only around the end of the first postnatal week. Likewise, mRNA expression of activity-regulated cytoskeletonassociated protein (Arc), an immediate-early gene whose expression is partly regulated by BDNF, also decreased in the MS group along with the reduction in BDNF expression. On the contrary, mRNA expression of tropomyosinrelated kinase B (TrkB), which is a BDNF receptor, was scarcely altered, while its protein expression decreased in the MS group only during the weaning period. In addition, MS reduced mRNA levels of glutamic acid decarboxylase (GAD) 65, a GABA synthesizing enzyme, only during the weaning period. Our results suggest that repeated MS temporarily attenuates BDNF signaling in the mPFC during early brain development. BDNF plays a crucial role in the development of inhibitory neurons; therefore, transient attenuation of BDNF signaling may cause delays in GABAergic neuron development in the mPFC.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 60%

Section: Animals and Maternal Separation Proceduresmentioning

confidence: 99%

Section: Tissue Sampling For Real-time Rt-pcr and Western Blotmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development

Tenkumo

Ohta

Suzuki

et al. 2020

Heliyon

Self Cite

View full text Add to dashboard Cite

show abstract

Infant ultrasonic vocalizations predict adolescent social behavior in rats: Effects of early life adversity

Granata

Valentine

Hirsch

et al. 2022

Developmental Psychobiology

View full text Add to dashboard Cite

Early life adversity (ELA) increases risk for psychopathologies that often manifest during adolescence and involve disrupted social functioning. ELA affects development of the prefrontal cortex (PFC), which plays a role in social behavior. PFC oxytocin and vasopressin are important regulators of, first, mother-infant attachment, and, later, social behavior, and are implicated in psychiatric disorders. Here, we tested whether infant social communication is predictive of PFC development and adolescent social behavior. We used the limited bedding (LB) ELA model in rats during postnatal days (P)2-14, and measured isolation-induced ultrasonic vocalizations (USVs) at P10 to characterize differences in an early social response. Rats were tested for dyadic social interaction in adolescence (P34). Adolescent oxytocin receptor (Oxtr) and argininevasopressin receptor 1a mRNA were measured in the PFC. Relationships between infant USVs, adolescent behavior, and gene expression were assessed. LB-reared rats exhibited fewer USVs at P10. While social behaviors were not robustly affected by rearing, fewer total and complex-type infant USVs predicted fewer interactions in adolescence. LB increased Oxtr in both sexes but Oxtr was not directly predicted by USVs.Findings support the use of USVs as indicators of differential early life experience in rodents, toward further characterization of early factors associated with vulnerability.

show abstract

Distinct roles of the left and right prelimbic cortices in the modulation of ethanol consumption in male mice under acute and chronic social defeat stress

Canto-de-Souza,

Baptista-de-Souza,

Nunes-de-Souza

et al. 2024

Psychopharmacology

View full text Add to dashboard Cite

The effects of early life stress on the excitatory/inhibitory balance of the medial prefrontal cortex

Cited by 41 publications

References 41 publications

Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development

Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development

Infant ultrasonic vocalizations predict adolescent social behavior in rats: Effects of early life adversity

Distinct roles of the left and right prelimbic cortices in the modulation of ethanol consumption in male mice under acute and chronic social defeat stress

Contact Info

Product

Resources

About