An Enriched Environment Reduces Chronic Stress-Induced Visceral Pain Through Modulating Microglial Activity in the Central Nucleus of the Amygdala

2021 ◽  
Author(s):  
Tian Yuan ◽  
Albert Orock ◽  
Beverley Greenwood-Van Meerveld
Keyword(s):  
Chronic Stress ◽  
Environmental Enrichment ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Female Rats ◽  
Central Nucleus ◽  
Dorsal Margin ◽  
Protective Effects ◽  
Male And Female Rats ◽  
Synaptic Pruning

Cognitive behavioral therapy (CBT) improves the quality of life for patients with brain-gut disorders, however, the underlying mechanisms of CBT remain to be explored. Previously we showed that environmental enrichment (EE), an experimental paradigm that mirrors positive behavioral intervention, ameliorates chronic stress-induced visceral hypersensitivity in a rodent model via mechanisms involving altered activity in the central nucleus of amygdala (CeA). In the present study, we investigated whether microglia-mediated synaptic plasticity in the CeA is a potential mechanism underlying the protective effects of EE against stress-induced visceral hypersensitivity. We sterotaxically implanted corticosterone (CORT) micropellets onto the dorsal margin of the CeA shown previously to induce colonic hypersensitivity. Animals were housed in EE cages or standard cages for 14 days following CORT implantation. Visceral sensitivity was assessed via visceromotor behavioral response to colorectal distension. Microglial morphology, microglia-mediated synaptic engulfment and the expression of synaptic pruning-related signals C1q, C3 and C3R were measured using immunofluorescence and RNAscope assay. We found that housing CORT implanted rats in EE cages for 14 days attenuated visceral hypersensitivity in both male and female rats as compared to control rats maintained in standard housing. EE reduced CORT-induced microglial remodeling and microglia-mediated synaptic pruning with reduced C1q and CR3, but not C3, expression. Our data suggest that exposure to EE is sufficient to ameliorate stress-induced visceral pain via reducing amygdala microglia-modulated neuronal plasticity.

scholarly journals Estrogen re-enhanced prenatal stress-related visceral sensitization and pain regulation

2020 ◽  
Author(s):  
Jinghong Chen ◽  
Ying Sun ◽  
Jinbao Wei ◽  
Peijun Ju ◽  
Qinjie Li ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Prenatal Stress ◽  
Pain Sensitivity ◽  
Visceral Pain ◽  
Afferent Fiber ◽  
Visceral Hypersensitivity ◽  
Female Rats ◽  
Primary Afferent

Abstract Background: Visceral pain is one of the most common sign of irritable bowel syndrome (IBS). Chronic stress during pregnancy may increase visceral pain sensitivity of offspring in a sexdependent way. Combining adult stress in offspring will increase this sensitivity. Based on the evidence implicating estrogen exacerbates visceral hypersensitivity in female rodents in pre-clinical models, we predicted that chronic prenatal stress (CPS) plus chronic adult stress (CAS) will maximize visceral pain sensitivity; and estrogen plays an important role in this hyperalgesia.Methods: The CPS plus CAS rodent model was established in which the balloon was used to distend colorectum. Meanwhile, the single fiber recording in vivo and patch-clamp experiments in vitro were used to monitor neuronal activity. The RT-PCR, Western Blot, and Immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity and molecular or transmission changes. We use Ovariectomy and Letrozole to treate female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization. Letrozole mainly used to reduce estrogen levels.Results: As predicted, CPS significantly increased single unit afferent fiber activity in L6-S2 dorsal roots in response. Activity was further enhanced by CAS. And the activity in offspring females was significantly greater than the males. Besides, the excitability of colon-projecting dorsal root ganglion (DRG) neurons increases in CPS + CAS rats that was associated with a decrease in transient A-type K+ current. Letrozole treatment decreases the colon DRG neuron excitability in females by decreasing the estrogen levels. Conclusions: This study adds to the growing evidence for the development of chronic stress induced visceral hypersensitivity in female, which involves estrogen-dependent sensitization of primary afferent colon neurons. Understanding this neurophysiological mechanisms will spur the development of female pain specific therapies.

scholarly journals Pair-housing of male and female rats during chronic stress exposure results in gender-specific behavioral responses

2005 ◽  
Vol 47 (5) ◽  
pp. 620-628 ◽  
Author(s):  
C. Westenbroek ◽  
T.A.B. Snijders ◽  
J.A. den Boer ◽  
M. Gerrits ◽  
D.S. Fokkema ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Behavioral Responses ◽  
Female Rats ◽  
Stress Exposure ◽  
Male And Female ◽  
Male And Female Rats ◽  
Gender Specific

scholarly journals Overexpression of Corticotropin Releasing Factor in the Central Nucleus of the Amygdala Advances Puberty and Disrupts Reproductive Cycles in Female Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3934-3944 ◽  
Author(s):  
X. F. Li ◽  
M. H. Hu ◽  
S. Y. Li ◽  
C. Geach ◽  
A. Hikima ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Pulse Generator ◽  
Female Rats ◽  
Central Nucleus ◽  
Ovariectomized Rats ◽  
Human Society ◽  
Central Administration ◽  
Corticosterone Secretion ◽  
Stress Changes

Abstract Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal axis. Because CRF expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic GnRH pulse generator, we tested the hypothesis that overexpression of CRF in the CeA of female rats alters anxiety behavior, dysregulates the HPA axis response to stress, changes pubertal timing, and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of preweaning (postnatal day 12) female rats. Overexpression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats overexpressing CRF. Despite the absence of change in basal corticosterone secretion or induced by stress (lipopolysaccharide or restraint), overexpression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in postpubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.

Chronic Stress Effects on Sexual Behavior in Male and Female Rats

1998 ◽  
Vol 61 (4) ◽  
pp. 405-412 ◽  
Author(s):  
Boris B. Gorzalka ◽  
Laura A. Hanson ◽  
Lori A. Brotto
Keyword(s):  
Sexual Behavior ◽  
Chronic Stress ◽  
Female Rats ◽  
Male And Female ◽  
Stress Effects ◽  
Male And Female Rats

Environmental enrichment attenuates nicotine behavioral sensitization in male and female rats.

2014 ◽  
Vol 22 (4) ◽  
pp. 356-363 ◽  
Author(s):  
Kristen R. Hamilton ◽  
Brenda M. Elliott ◽  
Sarah Shafer Berger ◽  
Neil E. Grunberg
Keyword(s):  
Environmental Enrichment ◽  
Behavioral Sensitization ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Differential Effects of Extended Exercise and Memantine Treatment on Adult Neurogenesis in Male and Female Rats

2018 ◽  
Author(s):  
Shaina P Cahill ◽  
John Darby Cole ◽  
Ru Qi Yu ◽  
Jack Clemans-Gibbon ◽  
Jason S Snyder
Keyword(s):  
Nmda Receptor ◽  
Cell Density ◽  
Adult Neurogenesis ◽  
Environmental Enrichment ◽  
Antidepressant Drugs ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Age Related ◽  
Males And Females

ABSTRACTThe creation of new neurons in adulthood has potential for treating a number of disorders that are characterized by neurodegeneration or impaired plasticity. Animal models of reduced neurogenesis, and studies of the volume and structural integrity of the hippocampus in humans, suggest a possible therapeutic role for adult neurogenesis in age-related cognitive decline, depression, and schizophrenia. Research over the past 20 years has identified a number of approaches for enhancing adult neurogenesis, such as exercise, NMDA receptor antagonists, antidepressant drugs and environmental enrichment. However, despite the chronic nature of many disorders that impact the human hippocampus, most animal studies have only examined the efficacy of neurogenic treatments over relatively short timescales (∼1 month or less). Additionally, investigations into the regulation of neurogenesis typically include only 1 sex, even though many disorders that affect the hippocampus differentially impact males and females. Here, we therefore tested whether two known pro-neurogenic treatments, running and the NMDA receptor antagonist, memantine, could lead to long-term increases in neurogenesis in male and female rats. We found that continuous access to a running wheel (cRUN) initially increased neurogenesis in both sexes, but effects were minimal after 1 month (both sexes) and completely absent after 5 months (males). Similarly, a single injection of memantine (sMEM) only transiently increased adult neurogenesis in both males and females. To determine whether extended increases in neurogenesis were possible with 2 months of RUN and MEM treatments, we subjected rats to interval running (iRUN), weekly memantine injections (mMEM), or combined treatments (iRUN-mMEM, mMEM-iRUN). We found that 2 months of iRUN increased DCX+ cell density in females but iRUN-mMEM treatment increased DCX+ cell density in males. However, analyses with thymidine analogs revealed that neurogenesis was minimally increased during the initial phases of the 2 month treatments. Collectively, our findings identify sex differences in the efficacy of neurogenic manipulations, which may be relevant for designing plasticity-promoting treatments that target the hippocampus.

scholarly journals Chronic Stress During Adolescence Blunts the Exercise-Induced Expression of Thyroid Hormone-Target Genes in Metabolically Active Tissues of Male and Female Rats

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A974-A974
Author(s):  
Marco Antonio Parra-Montes de Oca ◽  
Karen Lissette Garduño-Morales ◽  
Patricia Joseph-Bravo
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Chronic Stress ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Dependent Manner ◽  
Male And Female ◽  
Male And Female Rats ◽  
Exercise Induced ◽  
Hpt Axis

Abstract Voluntary exercise activates HPT axis1, that contributes to energy mobilization and energy expenditure. Chronic stress in adulthood inhibits HPT response to voluntary wheel running in a sex dependent manner, inhibiting lipolysis of WAT2. We evaluated the effect of chronic stress during adolescence on HPT axis response to voluntary exercise in adulthood3, with emphasis on metabolic response in skeletal muscle and WAT. Wistar male and female rats (N=36 per sex) were divided in an undisturbed group (Control, C; n=18) and one chronic variable stress during adolescence group (CVS; n=18) (males: PND 30-70; females: PND 30-60). As adults (males: PND 84; females: PND: 74) rats were divided in: 1) exercise group: rats placed individually in a cage with a running wheel per 14 nights, 2) sedentary group with ad libitum feeding, 3) sedentary pair-fed group offered the same amount of food consumed by the exercised group, and kept in individual cages during 14 nights (6 rats/group). WAT weight was determined at sacrifice, hormones quantified by RIA and ELISA, gene expression by RT-PCR. Exercise-induced loss of fat mass was not detected in CVS rats. Exercise decreased corticosterone levels in C males and females of both treatments, supporting sex difference on HPA axis reprogramming by CVS. HPT axis response to voluntary exercise is attenuated by CVS also in a sex dimorphic manner: CVS decreased Trh expression in hypothalamic paraventricular nucleus and no changes in thyroid hormones concentration in males, whereas in females, slightly increased TSH, T4 and T3 levels. Sex also influenced the response of skeletal muscle and WAT to CVS. Dio2 and Pgc1a slightly increased expression in skeletal muscle of males, not of females. Adrb3 expression in WAT increased in females, but not in males; exercise-induced stimulation of Hsl expression was not observed in either sex after CVS. These results suggest that CVS imposed during rat adolescence inhibits the responses to voluntary exercise of HPT axis activity of thyroid hormone-targets in WAT and skeletal muscle in sex dependent manner. These changes could lead to reduced mobilization and the utilization of energy fuels coincident with the fatigue observed after exercise in patients with subclinical or clinical hypothyroidism. (Funded: CONACYT 284883, DGAPA IN213419)1Uribe, Endocrinology 155:2020-2030, 2014.2Parra, Front Endocrinol 10(418):1-13, 2019.3Parra, J Endocr Soc 4(Abstract Supp) Abstract SAT-451, 2020.

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