scholarly journals Sex-specific vasopressin signaling buffers stress-dependent synaptic changes in female mice

2020 ◽  
Author(s):  
Spencer P. Loewen ◽  
Dinara Baimoukhametova ◽  
Jaideep S. Bains
Keyword(s):  
Social Networks ◽  
Critical Role ◽  
Well Being ◽  
Local Form ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Social Buffering ◽  
Female Mice ◽  
Glutamate Synapses ◽  
Stress Dependent

AbstractIn many species, social networks provide benefit for both the individual and the collective. In addition to transmitting information to others, social networks provide an emotional buffer for distressed individuals. Our understanding about the cellular mechanisms that contribute to buffering is poor. Stress has consequences for the entire organism, including a robust change in synaptic plasticity at glutamate synapses onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN). In females, however, this stress-induced metaplasticity is buffered by the presence of a naïve partner. This buffering may be due to discrete behavioral interactions, signals in the context in which the interaction occurs (i.e. olfactory cues), or it may be influenced by local signaling events in the PVN. Here, we show that local vasopressin (VP) signaling in PVN buffers the short-term potentiation (STP) at glutamate synapses after stress. This social buffering of metaplasticity, which requires the presence of another individual, was prevented by pharmacological inhibition of the VP 1a receptor in female mice. Exogenous VP mimicked the effects of social buffering and reduced STP in CRHPVN neurons from females but not males. These findings implicate VP as a potential mediator of social buffering in female mice.Significance StatementIn many organisms, including rodents and humans, social groups are beneficial to overall health and well-being. Moreover, it is through these social interactions that the harmful effects of stress can be mitigated—a phenomenon known as social buffering. In the present study, we describe a critical role for the neuropeptide vasopressin in social buffering of synaptic metaplasticity in stress-responsive corticotropin-releasing hormone neurons in female mice. These effects of vasopressin do not extend to social buffering of stress behaviors, suggesting this is a very precise and local form of sex-specific neuropeptide signaling.

scholarly journals Spatiotemporal chloride dynamics in hypothalamic CRHPVN neurons

2020 ◽  
Author(s):  
Aaron Lanz ◽  
Grant Gordon ◽  
Jaideep Bains
Keyword(s):  
Inhibitory Synapses ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Inhibitory Neurotransmission ◽  
Stress Dependent ◽  
The Brain

AbstractChloride (Cl-) dynamics shape inhibitory neurotransmission in the brain. In the hypothalamus, GABA signalling onto corticotropin-releasing hormone (CRHPVN) neurons can switch from inhibitory to excitatory during stress. Although Cl- fluctuations mediate this stress-dependent shift in GABA signalling, the underlying Cl- dynamics are poorly understood. Here, using a novel optogenetic strategy to load intracellular Cl- using halorhodopsin, we demonstrate that KCC2 rapidly restores Cl- setpoints in CRHPVN neurons from naïve animals, but that this process is slowed following stress. Further, we report that somatic Cl- homeostasis remains intact after stress. Our results strongly support the idea that KCC2 functions primarily to maintain Cl- setpoints and that inhibitory synapses onto dendritic and somatic compartments of CRHPVN neurons are differentially regulated during stress.

scholarly journals EPAC2 is required for corticotropin-releasing hormone-mediated spine loss

2019 ◽  
Author(s):  
Zhong Xie ◽  
Peter Penzes ◽  
Deepak P. Srivastava
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Acute Stress ◽  
Critical Role ◽  
Small Gtpase ◽  
Corticotropin Releasing Hormone ◽  
Rapid Loss ◽  
Primary Cortical Neurons ◽  
Releasing Hormone

AbstractCorticotropin-releasing hormone (CRH) is produced in response to stress. This hormone plays a key role in mediating neuroendocrine, behavioral, and autonomic responses to stress. The CRH receptor 1 (CRHR1) is expressed in multiple brain regions including the cortex and hippocampus. Previous studies have shown that activation of CRHR1 by CRH results in the rapid loss of dendritic spines. Exchange protein directly activated by cAMP (EPAC2, also known as RapGEF4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rap, has been linked with CRHR1 signaling. EPAC2 plays a critical role in regulating dendritic spine morphology and number in response to several extracellular signals. But whether EPAC2 links CRHR1 with dendritic spine remodeling is unknown. Here we show that CRHR1 is highly enriched in the dendritic spines of primary cortical neurons. Furthermore, we find that EPAC2 and CRHR1 co-localize in cortical neurons. Critically, short hairpin RNA-mediated knockdown of Epac2 abolished CRH-mediated spine loss in primary cortical neurons. Taken together, our data indicate that EPAC2 is required for the rapid loss of dendritic spines induced by CRH. These findings identify a novel pathway by which acute exposure to CRH may regulate synaptic structure and ultimately responses to acute stress.

scholarly journals MeCP2 haplodeficiency and early-life stress interaction on anxiety-like behavior in adolescent female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
María Abellán-Álvaro ◽  
Oliver Stork ◽  
Carmen Agustín-Pavón ◽  
Mónica Santos
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Hypothalamic Nucleus ◽  
Corticotropin Releasing Hormone ◽  
Wild Type ◽  
Releasing Hormone ◽  
Complex Disorders ◽  
Female Mice

Abstract Background Early-life stress can leave persistent epigenetic marks that may modulate vulnerability to psychiatric conditions later in life, including anxiety, depression and stress-related disorders. These are complex disorders with both environmental and genetic influences contributing to their etiology. Methyl-CpG Binding Protein 2 (MeCP2) has been attributed a key role in the control of neuronal activity-dependent gene expression and is a master regulator of experience-dependent epigenetic programming. Moreover, mutations in the MECP2 gene are the primary cause of Rett syndrome and, to a lesser extent, of a range of other major neurodevelopmental disorders. Here, we aim to study the interaction of MeCP2 with early-life stress in variables known to be affected by this environmental manipulation, namely anxiety-like behavior and activity of the underlying neural circuits. Methods Using Mecp2 heterozygous and wild-type female mice we investigated the effects of the interaction of Mecp2 haplodeficiency with maternal separation later in life, by assessing anxiety-related behaviors and measuring concomitant c-FOS expression in stress- and anxiety-related brain regions of adolescent females. Moreover, arginine vasopressin and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus were analyzed for neuronal activation. Results In wild-type mice, maternal separation caused a reduction in anxiety-like behavior and in the activation of the hypothalamic paraventricular nucleus, specifically in corticotropin-releasing hormone-positive cells, after the elevated plus maze. This effect of maternal separation was not observed in Mecp2 heterozygous females that per se show decreased anxiety-like behavior and concomitant decreased paraventricular nuclei activation. Conclusions Our data supports that MeCP2 is an essential component of HPA axis reprogramming and underlies the differential response to anxiogenic situations later in life.

scholarly journals Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 9908
Author(s):  
Willian O. dos Santos ◽  
Daniela O. Gusmao ◽  
Frederick Wasinski ◽  
Edward O. List ◽  
John J. Kopchick ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Growth Hormone Receptor ◽  
Acute Stress ◽  
Corticotropin Releasing Hormone ◽  
Male And Female ◽  
Releasing Hormone ◽  
Female Mice ◽  
Physiological Importance ◽  
Corticosterone Secretion

Corticotropin-releasing hormone (CRH) cells are the dominant neuronal population responsive to the growth hormone (GH) in the paraventricular nucleus of the hypothalamus (PVH). However, the physiological importance of GH receptor (GHR) signaling in CRH neurons is currently unknown. Thus, the main objective of the present study was to investigate the consequences of GHR ablation in CRH-expressing cells of male and female mice. GHR ablation in CRH cells did not cause significant changes in body weight, body composition, food intake, substrate oxidation, locomotor activity, glucose tolerance, insulin sensitivity, counterregulatory response to 2-deoxy-D-glucose and ghrelin-induced food intake. However, reduced energy expenditure was observed in female mice carrying GHR ablation in CRH cells. The absence of GHR in CRH cells did not affect anxiety, circadian glucocorticoid levels or restraint-stress-induced corticosterone secretion and activation of PVH neurons in both male and female mice. In summary, GHR ablation, specifically in CRH-expressing neurons, does not lead to major alterations in metabolism, hypothalamic–pituitary–adrenal axis, acute stress response or anxiety in mice. Considering the previous studies showing that central GHR signaling regulates homeostasis in situations of metabolic stress, future studies are still necessary to identify the potential physiological importance of GH action on CRH neurons.

Corticotropin releasing hormone (CRH) is a proinflammatory peptide in mouse ileum

2001 ◽  
Vol 120 (5) ◽  
pp. A38-A39
Author(s):  
M WLK ◽  
C WANG ◽  
M VENICHAKI ◽  
S KUHNTMOORE ◽  
D ZHAO ◽  
...  
Keyword(s):  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Mouse Ileum
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