Age-Specific Modulation of Prefrontal Cortex LTP by Glucocorticoid Receptors Following Brief Exposure to HFD

The corticolimbic circuits in general and the medial prefrontal cortex in particular, undergo maturation during juvenility. It is thus expected that environmental challenges in forms of obesogenic diet can exert different effects in juvenile animals compared to adults. Further, the relationship between glucocorticoids and obesity has also been demonstrated in several studies. As a result, glucocorticoid receptor (GR) antagonists are currently being tested as potential anti-obesity agents. In the present study, we examined the effects of short-term exposure to high-fat diet (HFD) on prefrontal long-term potentiation (LTP) in both juvenile and adult rats, and the role of glucocorticoid receptors (GRs) in modulating these effects. We found HFD impaired prefrontal LTP in both juveniles and adults, but the effects of GR modulation were age- and diet-dependent. Specifically, GR antagonist RU-486 reversed the impairment of LTP in juvenile animals following HFD, and had no effect on control-diet animals. In adult animals, RU-486 has no effect on HFD-impaired LTP, but abolished LTP in control-diet animals. Furthermore, impairments in the prefrontal LTP following HFD are involved with an increase in the mPFC GR levels only in the juveniles. Further, we found that in vivo application of GR agonists into adult mPFC rescued HFD-induced impairment in LTP, suggesting that these receptors might represent strategic therapeutic targets to potentially combat obesity and metabolic related disorder.

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Sialic Acid and Sialylated Oligosaccharide Supplementation during Lactation Improves Learning and Memory in Rats

Nutrients ◽

10.3390/nu10101519 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1519 ◽

Cited By ~ 22

Author(s):

Elena Oliveros ◽

Enrique Vázquez ◽

Alejandro Barranco ◽

María Ramírez ◽

Agnes Gruart ◽

...

Keyword(s):

Cognitive Abilities ◽

Behavioral Assessment ◽

Long Term Potentiation ◽

Cognitive Outcomes ◽

Free Form ◽

Control Group ◽

Adult Rats ◽

Acetylneuraminic Acid ◽

One Year

Sialic acids (Sia) are postulated to improve cognitive abilities. This study evaluated Sia effects on rat behavior when administered in a free form as N-acetylneuraminic acid (Neu5Ac) or conjugated as 6′-sialyllactose (6′-SL). Rat milk contains Sia, which peaks at Postnatal Day 9 and drops to a minimum by Day 15. To bypass this Sia peak, a cohort of foster mothers was used to raise the experimental pups. A group of pups received a daily oral supplementation of Neu5Ac to mimic the amount naturally present in rat milk, and another group received the same molar amount of Sia as 6′-SL. The control group received water. After weaning, rats were submitted to behavioral evaluation. One year later, behavior was re-evaluated, and in vivo long-term potentiation (LTP) was performed. Brain samples were collected and analyzed at both ages. Adult rats who received Sia performed significantly better in the behavioral assessment and showed an enhanced LTP compared to controls. Within Sia groups, 6′-SL rats showed better scores in some cognitive outcomes compared to Neu5Ac rats. At weaning, an effect on polysialylated-neural cell adhesion molecule (PSA-NCAM) levels in the frontal cortex was only observed in 6′-SL fed rats. Providing Sia during lactation, especially as 6′-SL, improves memory and LTP in adult rats.

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Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

Scientific Reports ◽

10.1038/s41598-020-63979-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Cleiton Lopes-Aguiar ◽

Rafael N. Ruggiero ◽

Matheus T. Rossignoli ◽

Ingrid de Miranda Esteves ◽

José Eduardo Peixoto-Santos ◽

...

Keyword(s):

Prefrontal Cortex ◽

Long Term Potentiation ◽

Term Potentiation

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Adult-onset hypothyroidism impairs paired-pulse facilitation and long-term potentiation of the rat dorsal hippocampo-medial prefrontal cortex pathway in vivo

Brain Research ◽

10.1016/j.brainres.2006.04.042 ◽

2006 ◽

Vol 1096 (1) ◽

pp. 53-60 ◽

Cited By ~ 30

Author(s):

L. Sui ◽

F. Wang ◽

B.M. Li

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Long Term Potentiation ◽

Adult Onset ◽

Paired Pulse ◽

Paired Pulse Facilitation ◽

Term Potentiation

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Supplementation with methyl donors during lactation to high-fat-sucrose-fed dams protects offspring against liver fat accumulation when consuming an obesogenic diet

Journal of Developmental Origins of Health and Disease ◽

10.1017/s204017441400035x ◽

2014 ◽

Vol 5 (5) ◽

pp. 385-395 ◽

Cited By ~ 25

Author(s):

P. Cordero ◽

F. I. Milagro ◽

J. Campion ◽

J. A. Martinez

Keyword(s):

Control Diet ◽

Liver Fat ◽

Chow Diet ◽

Mrna Levels ◽

High Fat ◽

Adult Rats ◽

Fat Accumulation ◽

Methyl Donors ◽

Methyl Donor ◽

Obesogenic Diet

Methyl donor supplementation has been reported to prevent obesity-induced liver fat accumulation in adult rats. We hypothesized that this protection could be mediated by perinatal nutrition. For this purpose, we assessed the response to an obesogenic diet (high-fat-sucrose, HFS) during adulthood depending on maternal diet during lactation. Female Wistar rats fed control diet during pregnancy were assigned to four postpartum dietary groups: control, control supplemented with methyl donors (choline, betaine, folic acid, vitamin B12), HFS and HFS supplemented with methyl donors. At weaning, the male offspring was transferred to a chow diet and at week 12th assigned to a control or a HFS diet during 8 weeks. The offspring whose mothers were fed HFS during lactation showed increased adiposity (19%,P<0.001). When fed the HFS diet as adults, offspring whose mothers were HFS supplemented had more body fat (23%,P<0.001) than those from HFS non-supplemented. However, they showed lower liver fat accumulation (−18%,P<0.001). Srebf1, Dnmt1 and Lepr liver mRNA levels increased after adulthood HFS feeding. In those animals HFS fed during adulthood, previous maternal HFS decreased Lepr and Dnmt1 expression levels when compared with c-HFS offspring, while the supplementation of control and HFS-fed dams, respectively, induced higher hepatic Mme and Lepr mRNA levels after adult HFS intake compared with hfs-HFS offspring. In conclusion, maternal HFS diet during lactation influenced the response to an obesogenic diet in the adult progeny. Interestingly, dietary methyl donor supplementation in lactating mothers fed an obesogenic diet reduced liver fat accumulation, but increased adipose tissue storage in adult HFS-fed offspring.

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Medial prefrontal cortex ablation results in impaired spatial memory and hippocampal long-term potentiation with increased functional connectivity in vivo

Frontiers in Neuroscience ◽

10.3389/conf.fnins.2015.89.00050 ◽

2015 ◽

Vol 9 ◽

Author(s):

Latif-Hernandez Amira ◽

Ahmed Tariq ◽

Callaerts-Vegh Zsuzsanna ◽

Lo Adrian ◽

Shah Disha ◽

...

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Spatial Memory ◽

Medial Prefrontal Cortex ◽

Long Term Potentiation ◽

Term Potentiation

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Effects of perfluorooctane sulfonate and its alternatives on long-term potentiation in the hippocampus CA1 region of adult rats in vivo

Toxicology Research ◽

10.1039/c5tx00184f ◽

2016 ◽

Vol 5 (2) ◽

pp. 539-546 ◽

Cited By ~ 18

Author(s):

Qian Zhang ◽

Wei Liu ◽

Qiao Niu ◽

Yu Wang ◽

Huimin Zhao ◽

...

Keyword(s):

Health Effects ◽

Perfluorooctane Sulfonate ◽

Long Term Potentiation ◽

Adult Rats ◽

Ca1 Region ◽

Term Potentiation

With the limited but ongoing usage of perfluorooctane sulfonate (PFOS), the health effects of both PFOS and its alternatives are far from being understood.

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In Vivo Roles for Matrix Metalloproteinase-9 in Mature Hippocampal Synaptic Physiology and Plasticity

Journal of Neurophysiology ◽

10.1152/jn.00202.2007 ◽

2007 ◽

Vol 98 (1) ◽

pp. 334-344 ◽

Cited By ~ 102

Author(s):

Ozlem Bozdagi ◽

Vanja Nagy ◽

Kimberly T. Kwei ◽

George W. Huntley

Keyword(s):

Synaptic Plasticity ◽

Proteolytic Activity ◽

Neutralizing Antibodies ◽

Long Term Potentiation ◽

Receptor Activation ◽

Synaptic Function ◽

Loss Of Function ◽

Adult Rats ◽

Area Ca1

Extracellular proteolysis is an important regulatory nexus for coordinating synaptic functional and structural plasticity, but the identity of such proteases is incompletely understood. Matrix metalloproteinases (MMPs) have well-known, mostly deleterious roles in remodeling after injury or stroke, but their role in nonpathological synaptic plasticity and function in intact adult brains has not been extensively investigated. Here we address the role of MMP-9 in hippocampal synaptic plasticity using both gain- and loss-of-function approaches in urethane-anesthetized adult rats. Acute blockade of MMP-9 proteolytic activity with inhibitors or neutralizing antibodies impairs maintenance, but not induction, of long-term potentiation (LTP) at synapses formed between Schaffer-collaterals and area CA1 dendrites. LTP is associated with significant increases in levels of MMP-9 and proteolytic activity within the potentiated neuropil. By introducing a novel application of gelatin-substrate zymography in vivo, we find that LTP is associated with significantly elevated numbers of gelatinolytic puncta in the potentiated neuropil that codistribute with immunolabeling for MMP-9 and for markers of synapses and dendrites. Such increases in proteolytic activity require NMDA receptor activation. Exposing intact area CA1 neurons to recombinant-active MMP-9 induces a slow synaptic potentiation that mutually occludes, and is occluded by, tetanically evoked potentiation. Taken together, our data reveal novel roles for MMP-mediated proteolysis in regulating nonpathological synaptic function and plasticity in mature hippocampus.

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Glucocorticoid receptors in the prefrontal cortex regulate dopamine efflux to stress via descending glutamatergic feedback to the ventral tegmental area

The International Journal of Neuropsychopharmacology ◽

10.1017/s1461145713000187 ◽

2013 ◽

Vol 16 (8) ◽

pp. 1799-1807 ◽

Cited By ~ 21

Author(s):

Kelly A. Butts ◽

Anthony G. Phillips

Keyword(s):

Prefrontal Cortex ◽

Ventral Tegmental Area ◽

Glucocorticoid Receptors ◽

Acute Stress ◽

Pyramidal Cells ◽

Gaba Release ◽

Underlying Mechanism ◽

Ventral Tegmental ◽

Glutamate Efflux

Abstract Enhanced dopamine (DA) efflux in the medial prefrontal cortex (mPFC) is a well-documented response to acute stress. We have previously shown that glucocorticoid receptors in the mPFC regulate stress-evoked DA efflux but the underlying mechanism is unknown. DA neurons in the ventral tegmental area (VTA) receive excitatory input from and send reciprocal projections to the mPFC. We hypothesize that blockade of prefrontal glucocorticoid receptors can reduce activity of descending glutamatergic input to the VTA, thereby attenuating stress-evoked DA efflux in the mPFC. Using in vivo microdialysis, we demonstrate that acute tail-pinch stress leads to a significant increase in glutamate efflux in the VTA. Blockade of prefrontal glucocorticoid receptors with the selective antagonist CORT 108297 attenuates stress-evoked glutamate efflux in the VTA together with DA efflux in the mPFC. Furthermore, blockade of ionotrophic glutamate receptors in the VTA attenuates stress-evoked DA efflux in the mPFC. We also examine the possible role of glucocorticoid-induced synthesis and release of endocannabinoids acting presynaptically via cannabinoid CB1 receptors to inhibit GABA release onto prefrontal pyramidal cells, thus enhancing descending glutamatergic input to the VTA leading to an increase in mPFC DA efflux during stress. However, administration of the cannabinoid CB1 receptor antagonist into the mPFC does not attenuate stress-evoked DA efflux in the mPFC. Taken together, our data indicate that glucocorticoids act locally within the mPFC to modulate mesocortical DA efflux by potentiation of glutamatergic drive onto DA neurons in the VTA.

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Sex differences in the behavioral and synaptic consequences of a single exposure to cannabinoid at puberty and adulthood

10.1101/415067 ◽

2018 ◽

Author(s):

Milene Borsoi ◽

Antonia Manduca ◽

Anissa Bara ◽

Olivier Lassalle ◽

Anne-Laure Pelissier-Alicot ◽

...

Keyword(s):

Sex Differences ◽

Social Behavior ◽

Pyramidal Neurons ◽

Long Term Potentiation ◽

Adult Males ◽

Adult Rats ◽

Term Potentiation ◽

Cannabis Consumption

AbstractHeavy cannabis consumption among adolescents is associated with significant and lasting neurobiological, psychological and health consequences that depend on the age of first use. Chronic exposure to cannabinoid (CB) agonists during adolescence alters social behavior and prefrontal cortex (PFC) activity in adult rats. However, sex differences on social behavior as well as PFC synaptic plasticity after acute CB activation remain poorly explored. Here, we determined the consequences of a single CB activation differently affects PFC in males and females by assessing social behavior and PFC neuronal and synaptic functions in rats during pubertal or adulthood periods, 24h after a single in-vivo cannabinoid exposure (SCE). During puberty, SCE reduced play behavior in females but not males. In contrast, SCE impaired sociability in both sexes at adulthood. General exploration and memory recognition remained normal at both ages and both sexes. At the synaptic level, SCE ablated endocannabinoid-mediated long-term depression (eCB-LTD) in the PFC of females of both ages and heightened excitability of PFC pyramidal neurons at adulthood, while males were spared. In contrast, SCE was associated to impaired long-term potentiation in adult males. Together, the data indicate behavioral and synaptic sex differences in response to a single in-vivo exposure to cannabinoid at puberty and adulthood.

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