Sex-Specific Anxiety and Prefrontal Cortex Glutamatergic Dysregulation Are Long-Term Consequences of Pre-and Postnatal Exposure to Hypercaloric Diet in a Rat Model

Both maternal and early life malnutrition can cause long-term behavioral changes in the offspring, which depends on the caloric availability and the timing of the exposure. Here we investigated in a rat model whether a high-caloric palatable diet given to the mother and/or to the offspring during the perinatal and/or postnatal period might dysregulate emotional behavior and prefrontal cortex function in the offspring at adult age. To this end, we examined both anxiety responses and the mRNA/protein expression of glutamatergic, GABAergic and endocannabinoid signaling pathways in the prefrontal cortex of adult offspring. Male animals born from mothers fed the palatable diet, and who continued with this diet after weaning, exhibited anxiety associated with an overexpression of the mRNA of Grin1, Gria1 and Grm5 glutamate receptors in the prefrontal cortex. In addition, these animals had a reduced expression of the endocannabinoid system, the main inhibitory retrograde input to glutamate synapses, reflected in a decrease of the Cnr1 receptor and the Nape-pld enzyme. In conclusion, a hypercaloric maternal diet induces sex-dependent anxiety, associated with alterations in both glutamatergic and cannabinoid signaling in the prefrontal cortex, which are accentuated with the continuation of the palatable diet during the life of the offspring.

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Perinatal THC Exposure via Lactation Induces Lasting Alterations to Social Behavior and Prefrontal Cortex Function in Rats at Adulthood

10.1101/2020.02.03.931733 ◽

2020 ◽

Cited By ~ 1

Author(s):

Andrew F Scheyer ◽

Milene Borsoi ◽

Olivier JJ Manzoni

Keyword(s):

Prefrontal Cortex ◽

Pyramidal Neurons ◽

Developmental Trajectories ◽

Long Term Potentiation ◽

Postnatal Period ◽

Synaptic Function ◽

Female Rat ◽

Female Progeny ◽

Male And Female

AbstractCannabis is the world’s most widely abused illicit drug and consumption amongst women during and surrounding the period of pregnancy is increasing. Previously, we have shown that cannabinoid exposure via lactation during the early postnatal period disrupts early developmental trajectories of prefrontal cortex maturation and induces behavioral abnormalities during the first weeks of life in male and female rat progeny. Here, we investigated the lasting consequences of this postnatal cannabinoid exposure on synaptic and behavioral parameters in the adult offspring of Δ9-tetrahydrocannabinol (THC)-treated dams. At adulthood, these perinatally THC-exposed rats exhibits deficits in social discrimination accompanied by an overall augmentation of social exploratory behavior. These behavioral alterations were further correlated with multiple abnormalities in synaptic plasticity in the prefrontal cortex, including lost endocannabinoid-mediated long-term depression (LTD), lost long-term potentiation and augmented mGlu2/3-LTD. Finally, basic parameters of intrinsic excitability at prefrontal cortex pyramidal neurons were similarly altered by the perinatal THC exposure. Thus, perinatal THC exposure via lactation induces lasting deficits in behavior and synaptic function which persist into adulthood life in male and female progeny.

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Mechanism of Intermittent Theta-Burst Stimulation in Synaptic Pathology in the Prefrontal Cortex in an Antidepressant-Resistant Depression Rat Model

Cerebral Cortex ◽

10.1093/cercor/bhaa244 ◽

2020 ◽

Vol 31 (1) ◽

pp. 575-590

Author(s):

Chi-Wei Lee ◽

Han-Fang Wu ◽

Ming-Chia Chu ◽

Yueh-Jung Chung ◽

Wei-Chang Mao ◽

...

Keyword(s):

Prefrontal Cortex ◽

Rat Model ◽

Synaptic Function ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Long Term Depression ◽

Synaptic Pathology ◽

Resistant Depression ◽

Theta Burst

Abstract Intermittent theta-burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation, is considered a potential therapy for treatment-resistant depression. The synaptic mechanism of iTBS has long been known to be an effective method to induce long-term potentiation (LTP)-like plasticity in humans. However, there is limited evidence as to whether the antidepressant effect of iTBS is associated with change in synaptic function in the prefrontal cortex (PFC) in preclinical study. Hence, we applied an antidepressant (i.e., fluoxetine)-resistant depression rat model induced by severe foot-shocks to investigate the antidepressant efficacy of iTBS in the synaptic pathology. The results showed that iTBS treatment improved not only the impaired LTP, but also the aberrant long-term depression in the PFC of antidepressant-resistant depression model rats. Moreover, the mechanism of LTP improvement by iTBS involved downstream molecules of brain-derived neurotrophic factor, while the mechanism of long-term depression improvement by iTBS involved downstream molecules of proBDNF. The aberrant spine morphology was also improved by iTBS treatment. This study demonstrated that the mechanism of the iTBS paradigm is complex and may regulate not only excitatory but also inhibitory synaptic effects in the PFC.

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Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

Neural Plasticity ◽

10.1155/2015/753179 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 4

Author(s):

Hiroshi Ueno ◽

Shunsuke Suemitsu ◽

Yosuke Matsumoto ◽

Motoi Okamoto

Keyword(s):

Prefrontal Cortex ◽

Time Course ◽

Sensory Deprivation ◽

Sensory System ◽

Postnatal Period ◽

Anterior Cingulate ◽

Improved Function ◽

Inhibitory Networks

Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

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Rat model of long term effects after fractionated (2Gy/day) 60Gy irradiation of rat liver

Zeitschrift für Gastroenterologie ◽

10.1055/s-0032-1331934 ◽

2013 ◽

Vol 51 (01) ◽

Author(s):

F Moriconi ◽

IA Malik ◽

A Amanzada ◽

G Ramadori ◽

CF Hess

Keyword(s):

Rat Liver ◽

Rat Model ◽

Long Term Effects

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Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects

Zeitschrift für Gastroenterologie ◽

10.1055/s-0033-1352735 ◽

2013 ◽

Vol 51 (08) ◽

Author(s):

M Rave-Fränk ◽

I Malik ◽

H Christiansen ◽

S Sultan ◽

N Naz ◽

...

Keyword(s):

Rat Model ◽

Long Term Effects

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Bone Manifestation of Faulty Perinatal Hormonal Imprinting: A Review

Current Pediatric Reviews ◽

10.2174/1573396315666181126110110 ◽

2019 ◽

Vol 15 (1) ◽

pp. 4-9

Author(s):

G. Csaba

Keyword(s):

Animal Behavior ◽

Binding Capacity ◽

Animal Experiments ◽

Osteoporotic Fractures ◽

Postnatal Period ◽

Hormonal Imprinting ◽

Adult Age ◽

Pathological Development ◽

Synthetic Hormones ◽

Critical Developmental Period

Hormonal imprinting takes place at the first encounter between the developing receptor and its target hormone and the encounter determines the receptor's binding capacity for life. In the critical period of development, when the window for imprinting is open, the receptor can be misdirected by related hormones, synthetic hormones, and industrial or communal endocrine disruptors which cause faulty hormonal imprinting with life-long consequences. Considering these facts, the hormonal imprinting is a functional teratogen provoking alterations in the perinatal (early postnatal) period. One single encounter with a low dose of the imprinter in the critical developmental period is enough for the formation of faulty imprinting, which is manifested later, in adult age. This has been justified in the immune system, in sexuality, in animal behavior and brain neurotransmitters etc. by animal experiments and human observations. This review points to the faulty hormonal imprinting in the case of bones (skeleton), by single or repeated treatments. The imprinting is an epigenetic alteration which is inherited to the progeny generations. From clinical aspect, the faulty imprinting can have a role in the pathological development of the bones as well, as in the risk of osteoporotic fractures, etc.

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Methadone effectively attenuates acute and long-term consequences of neonatal repetitive procedural pain in a rat model

Pediatric Research ◽

10.1038/s41390-020-01353-x ◽

2021 ◽

Author(s):

Nynke J. van den Hoogen ◽

Thomas J. de Geus ◽

Jacob Patijn ◽

Dick Tibboel ◽

Elbert A. Joosten

Keyword(s):

Rat Model ◽

Procedural Pain ◽

Long Term Consequences

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025 Sleep Disruption on an Orbital Shaker alters Glutamate in Prairie Vole Prefrontal Cortex

SLEEP ◽

10.1093/sleep/zsab072.024 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A11-A12

Author(s):

Carolyn Jones ◽

Randall Olson ◽

Alex Chau ◽

Peyton Wickham ◽

Ryan Leriche ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Prefrontal Cortex ◽

Early Life ◽

Autism Spectrum ◽

Prairie Vole ◽

Sleep Disruption ◽

Glutamatergic Synapses ◽

The Brain ◽

Orbital Shaker

Abstract Introduction Glutamate concentrations in the cortex fluctuate with the sleep wake cycle in both rodents and humans. Altered glutamatergic signaling, as well as the early life onset of sleep disturbances have been implicated in neurodevelopmental disorders such as autism spectrum disorder. In order to study how sleep modulates glutamate activity in brain regions relevant to social behavior and development, we disrupted sleep in the socially monogamous prairie vole (Microtus ochrogaster) rodent species and quantified markers of glutamate neurotransmission within the prefrontal cortex, an area of the brain responsible for advanced cognition and complex social behaviors. Methods Male and female prairie voles were sleep disrupted using an orbital shaker to deliver automated gentle cage agitation at continuous intervals. Sleep was measured using EEG/EMG signals and paired with real time glutamate concentrations in the prefrontal cortex using an amperometric glutamate biosensor. This same method of sleep disruption was applied early in development (postnatal days 14–21) and the long term effects on brain development were quantified by examining glutamatergic synapses in adulthood. Results Consistent with previous research in rats, glutamate concentration in the prefrontal cortex increased during periods of wake in the prairie vole. Sleep disruption using the orbital shaker method resulted in brief cortical arousals and reduced time in REM sleep. When applied during development, early life sleep disruption resulted in long-term changes in both pre- and post-synaptic components of glutamatergic synapses in the prairie vole prefrontal cortex including increased density of immature spines. Conclusion In the prairie vole rodent model, sleep disruption on an orbital shaker produces a sleep, behavioral, and neurological phenotype that mirrors aspects of autism spectrum disorder including altered features of excitatory neurotransmission within the prefrontal cortex. Studies using this method of sleep disruption combined with real time biosensors for excitatory neurotransmitters will enhance our understanding of modifiable risk factors, such as sleep, that contribute to the altered development of glutamatergic synapses in the brain and their relationship to social behavior. Support (if any) NSF #1926818, VA CDA #IK2 BX002712, Portland VA Research Foundation, NIH NHLBI 5T32HL083808-10, VA Merit Review #I01BX001643

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