scholarly journals Postnatal Overnutrition Induces Changes in Synaptic Transmission to Leptin Receptor-Expressing Neurons in the Arcuate Nucleus of Female Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2425
Author(s):  
Thais Tessari Zampieri ◽  
Tabata Mariz Bohlen ◽  
Marina Augusto Silveira ◽  
Larissa Campista Lana ◽  
Daniella G. de Paula ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neural Plasticity ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Postnatal Period ◽  
Pubertal Stage ◽  
Female Mice ◽  
Expression Of Genes ◽  
Cellular Excitability ◽  
Modulation Of Gene Expression

The adipocyte-derived hormone leptin is a potent neurotrophic factor that contributes to the neural plasticity and development of feeding circuitry, particularly in the arcuate nucleus of the hypothalamus (ARH). Postnatal overnutrition affects leptin secretion and sensitivity, but whether postnatal overnutrition produces changes in the development of the synaptic transmission to ARH neurons is currently unknown. We evaluated the excitatory and inhibitory currents to ARH leptin receptor (LepR)-expressing neurons in prepubertal, pubertal and adult female mice. The effects of postnatal overnutrition in the expression of genes that code ion channels subunits in the ARH were also evaluated. We observed that the transition from prepubertal to pubertal stage is characterized by a rise in both excitatory and inhibitory transmission to ARH LepR-expressing neurons in control mice. Postnatal overnutrition induces a further increase in the excitatory synaptic transmission in pubertal and adult animals, whereas the amplitude of inhibitory currents to ARH LepR-expressing cells was reduced. Postnatal overnutrition also contributes to the modulation of gene expression of N-methyl-D-aspartate, GABAB and ATP-sensitive potassium channel subunits in ARH. In summary, the synaptic transmission to ARH cells is profoundly influenced by postnatal overnutrition. Thus, increased adiposity during early postnatal period induces long-lasting effects on ARH cellular excitability.

Influence of photoperiod and gonadal status on food intake, adiposity, and gene expression of hypothalamic appetite regulators in a seasonal mammal

2007 ◽  
Vol 292 (1) ◽  
pp. R242-R252 ◽  
Author(s):  
Chantacha Anukulkitch ◽  
Alexandra Rao ◽  
Frank R. Dunshea ◽  
Dominique Blache ◽  
Gerald A. Lincoln ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Reproductive Axis ◽  
Pomc Gene ◽  
Gonadal Status ◽  
Long Photoperiod ◽  
Refractory Phase

We studied the effects of photoperiod on metabolic profiles, adiposity, and gene expression of hypothalamic appetite-regulating peptides in gonad-intact and castrated Soay rams. Groups of five to six animals were studied 6, 18, or 30 wk after switching from long photoperiod (LP: 16 h of light) to short photoperiod (SP: 8 h of light). Reproductive and metabolic indexes were measured in blood plasma. Expression of neuropeptide Y (NPY), proopiomelanocortin (POMC), and leptin receptor (ObRb) in the arcuate nucleus was measured using in situ hybridization. Testosterone levels of intact animals were low under LP, increased to a peak at 16 wk under SP, and then declined. Voluntary food intake (VFI) was high under LP in both intact and castrated animals, decreased to a nadir at 12–16 wk under SP, and then recovered, but only in intact rams as the reproductive axis became photorefractory to SP. NPY gene expression varied positively and POMC expression varied negatively with the cycle in VFI, with differences between intact and castrate rams in the refractory phase. ObRb expression decreased under SP, unrelated to changes in VFI. Visceral fat weight also varied between the intact and castrated animals across the cycle. We conclude that 1) photoperiodic changes in VFI reflect changes in NPY and POMC gene expression, 2) changes in ObRb gene expression are not necessarily determinants of changes in VFI, 3) gonadal status affects the pattern of VFI that changes with photoperiod, and 4) in the absence of gonadal factors, animals can eat less but gain adiposity.

Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth

2020 ◽  
Vol 34 (3) ◽  
pp. 370-379 ◽  
Author(s):  
Srisaiyini Kidnapillai ◽  
Ben Wade ◽  
Chiara C Bortolasci ◽  
Bruna Panizzutti ◽  
Briana Spolding ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Neurite Outgrowth ◽  
Neural Plasticity ◽  
Drug Combination ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Drug Effects ◽  
Differentially Expressed ◽  
Transcriptional Level ◽  
Expression Of Genes

Background: The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs. Methods: The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes ( n=20) and microRNAs ( n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes ( n=8). Independent samples t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at p<0.05. Results: We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( p<0.05). Putative target genes of these microRNAs targeted pathways including those identified as “neuron projection development” and “axonogenesis”. Many of the target genes are inhibitors of neurite outgrowth and neurogenesis and were downregulated following bipolar disorder drug combination treatment (all p<0.05). The bipolar disorder drug combination tended to decrease the expression of the target genes ( NOVA1, GRIN3A, and VIM), however this effect could be reversed by the application of microRNA inhibitors. Conclusions: We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.

scholarly journals Leptin receptor deficient female mice as a mouse model of heart failure with preserve ejection fraction

2019 ◽  
Vol 11 (2) ◽  
pp. 226-227 ◽  
Author(s):  
S. Guimbal ◽  
T. Couffinhal ◽  
P.L. Hollier ◽  
C. Chapouly ◽  
C. Caradu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mouse Model ◽  
Leptin Receptor ◽  
Preserve Ejection Fraction ◽  
Female Mice

scholarly journals Impairment of cerebellar long-term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yasushi Kishimoto ◽  
Moritoshi Hirono ◽  
Ryuichiro Atarashi ◽  
Suehiro Sakaguchi ◽  
Tohru Yoshioka ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Prion Protein ◽  
Neural Plasticity ◽  
Late Onset ◽  
Eyeblink Conditioning ◽  
Electrophysiological Study ◽  
Synaptic Function ◽  
Long Term Depression ◽  
Underlying Mechanisms

Abstract Prion protein (PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice also exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred. Thus, this electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. We showed that Ngsk Prnp0/0 mice exhibited normal paired-pulse facilitation but impaired long-term depression of excitatory synaptic transmission at synapses between parallel fibres and PCs. GABAA-mediated inhibitory postsynaptic currents recorded from PCs were also weakened in Ngsk Prnp0/0 mice. Furthermore, we confirmed that Ngsk Prnp0/0 mice (7–8-week-old) exhibited abnormalities in delay eyeblink conditioning. Our findings suggest that these alterations in both excitatory and inhibitory synaptic transmission to PCs caused deficits in delay eyeblink conditioning of Ngsk Prnp0/0 mice. Therefore, the Ngsk Prnp0/0 mouse model can contribute to study underlying mechanisms for impairments of synaptic transmission and neural plasticity, and cognitive deficits in the central nervous system.

scholarly journals Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pernille Barkholt ◽  
Kristoffer T. G. Rigbolt ◽  
Mechthilde Falkenhahn ◽  
Thomas Hübschle ◽  
Uwe Schwahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Molecular Mechanisms ◽  
Arcuate Nucleus ◽  
Gene Expression Signature ◽  
Global Gene Expression ◽  
Metabolic Effects ◽  
Expression Of Genes ◽  
Hypothalamic Arcuate Nucleus ◽  
Laser Capture

Abstract The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

scholarly journals The neurogenomic transition from territory establishment to parenting in a territorial female songbird

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Alexandra B. Bentz ◽  
Douglas B. Rusch ◽  
Aaron Buechlein ◽  
Kimberly A. Rosvall
Keyword(s):  
Breeding Season ◽  
Neural Plasticity ◽  
Behavioral Plasticity ◽  
Critical Role ◽  
Regulatory Pathways ◽  
Expression Of Genes ◽  
Trade Offs ◽  
Glucocorticoid Signaling ◽  
Seasonally Breeding ◽  
The Brain

Abstract Background The brain plays a critical role in upstream regulation of processes central to mating effort, parental effort, and self-maintenance. For seasonally breeding animals, the brain is likely mediating trade-offs among these processes within a short breeding season, yet research thus far has only explored neurogenomic changes from non-breeding to breeding states or select pathways (e.g., steroids) in male and/or lab-reared animals. Here, we use RNA-seq to explore neural plasticity in three behaviorally relevant neural tissues (ventromedial telencephalon [VmT], hypothalamus [HYPO], and hindbrain [HB]), comparing free-living female tree swallows (Tachycineta bicolor) as they shift from territory establishment to incubation. We additionally highlight changes in aggression-related genes to explore the potential for a neurogenomic shift in the mechanisms regulating aggression, a critical behavior both in establishing and maintaining a territory and in defense of offspring. Results HB had few differentially expressed genes, but VmT and HYPO had hundreds. In particular, VmT had higher expression of genes related to neuroplasticity and processes beneficial for competition during territory establishment, but down-regulated immune processes. HYPO showed signs of high neuroplasticity during incubation, and a decreased potential for glucocorticoid signaling. Expression of aggression-related genes also shifted from steroidal to non-steroidal pathways across the breeding season. Conclusions These patterns suggest trade-offs between enhanced activity and immunity in the VmT and between stress responsiveness and parental care in the HYPO, along with a potential shift in the mechanisms regulating aggression. Collectively, these data highlight important gene regulatory pathways that may underlie behavioral plasticity in females.

scholarly journals Three weeks of postweaning exercise in DIO rats produces prolonged increases in central leptin sensitivity and signaling

2009 ◽  
Vol 296 (3) ◽  
pp. R537-R548 ◽  
Author(s):  
Christa M. Patterson ◽  
Sebastien G. Bouret ◽  
Ambrose A. Dunn-Meynell ◽  
Barry E. Levin
Keyword(s):  
Food Intake ◽  
Receptor Binding ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
High Energy ◽  
Decrease Food Intake ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity

In rats selectively bred to develop diet-induced obesity (DIO) 3 wk of postweaning exercise reduces weight and adipose regain for 10 wk after exercise cessation, despite intake of 31% fat high-energy (HE) diet. To test the hypothesis that this effect is due to increased central leptin sensitivity, 4-wk-old DIO rats were fed the HE diet and left sedentary (Sed), exercised for 3 wk, and then remained sedentary for 10 additional weeks (Ex/Sed) or continued exercise for a full 13 wk (Ex). After 3 wk, leptin (5 mg/kg ip) induced a 36% decrease in 24-h food intake in Ex rats, while Sed rats had no change in 24-h intake. Ex rats also had 23% more leptin-induced phospho-STAT3 (pSTAT3)-expressing neurons in the arcuate nucleus (ARC) and 95% and 68% higher 125I-labeled leptin receptor binding in the ventromedial and dorsomedial nuclei than did Sed rats, respectively. At 7 wk after onset, leptin decreased 24-h intake by 20% in Ex and 24% in Ex/Sed rats without altering Sed intake. After a total of 13 wk, compared with Sed rats, Ex and Ex/Sed rats had 58% and 38% less fat, respectively, but leptin failed to decrease food intake in any group. Nevertheless, Ex, but not Ex/Sed rats, still had 32% more ARC leptin-induced pSTAT3-expressing neurons than Sed rats. These data suggest that brief postweaning exercise in DIO rats that are inherently leptin resistant causes a sustained resistance to obesity on HE diet, which is, in part, due to increased central leptin sensitivity.

218 DISTINCT EXPRESSION OF CALCIUM TRANSPORT CHANNELS, TRPV5, TRPV6, PMCA1, NCKX3, AND CaBP-9k IN THE DUODENUM, KIDNEY, AND PLACENTA DURING PREGNANCY

2015 ◽  
Vol 27 (1) ◽  
pp. 199
Author(s):  
H. Yang ◽  
C. Ahn ◽  
E.-B. Jeung
Keyword(s):  
Calcium Transport ◽  
Calcium Metabolism ◽  
Calcium Supplementation ◽  
Experimental Conditions ◽  
Comt Inhibition ◽  
Female Mice ◽  
Expression Of Genes ◽  
Concurrent Development ◽  
The Mean ◽  
Transport Channels

Preeclampsia is a pregnancy-specific disease characterised by concurrent development of hypertension, proteinuria, and oxidative stress in the placenta. Preeclampsia-like genetic models were also developed by modification of preeclampsia-related genes, such as catechol-O-methyltranferase (COMT). In the current study, we hypothesised that inhibition of COMT alters the expression of calcium transport genes and contributes to induction of a preeclampsia-like condition, and the treatment regimen such as calcium supplementation ameliorates the imbalanced calcium metabolism and preeclamptic symptoms. In this study, we induced COMT inhibition in mice during pregnancy to reproduce physiological conditions associated with preeclampsia. The expression of genes known as hypoxia biomarker, HIF-1a, was highly induced in the placenta of this model. The overexpression of HIF-1a demonstrates that our experimental conditions closely were similar with preeclampsia. We measured the expression of several calcium transporters (TRPV5, TRPV6, PMCA1, and CaBP-9k) in the placenta, duodenum, and kidney after COMT inhibition on gestation day 17.5 (GD 17.5). Twenty-eight mice were divided into 4 groups [Vehicle, calcium, RO41–0960, and RO41–0960 and calcium (2% of calcium carbonate)]. In addition, we evaluated the calcium transporters in the kidney and duodenum of nonpregnant female mice. The placental TRPV5,6, PMCA1, and CaBP-9k were investigated by real-time RT-PCR. All experimental data was presented mean ± standard error of the mean (s.e.m.); P-values were calculated using one-way ANOVA. Placental TRPV5, TRPV6 and PMCA1 expressions were significantly down-regulated by COMT inhibitor (ro41–0960). In addition, the reduced PMCA1 expression in the placenta was reversed by calcium supplementation. Duodenal expressions of TRPV5, TRPV6, and PMCA1 were significantly decreased in the COMT-inhibited mice, and slightly recovered after calcium supplementation. Renal expression of TRPV5, TRPV6, and PMCA1 was also decreased by COMT inhibition, while it was reversed by calcium supplementation to the level of control. Duodenal- and renal calcium transporting genes, TRPV5, TPRV6, PMCA1, and CaBP-9k, were down-regulated by COMT treatment in female mice. Taken together, these results indicate that physiological changes observed in COMT inhibition showed similar symptoms as in preeclampsia, which may be related with disturbance of calcium metabolism during pregnancy.

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