Adrenocortical and behavioural response to chronic restraint stress in neurokinin-1 receptor knockout mice

Delgado-Morales, Raúl; Río, Eva del; Gómez-Román, Almudena; Bisagno, Verónica; Nadal, Roser; Felipe, Carmen De; Armario, Antonio

doi:10.1016/j.physbeh.2011.10.008

Cited by 13 publications

(9 citation statements)

References 63 publications

(75 reference statements)

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“…This area expresses NK1R (23). To verify selective uptake of SP-LC/A, the cells were incubated with either BoNT/A-LC:SP (50 ng/ml) or BoNT/A-LC (50 ng/ml).…”

Section: Resultsmentioning

confidence: 99%

Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A

Mustafa

Anderson

Bokrand-Donatelli

et al. 2013

Pain

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Neuropathic pain is a debilitating condition resulting from damage to sensory transmission pathways in the peripheral and central nervous system. A potential new way of treating chronic neuropathic pain is to target specific pain processing neurons based on their expression of particular receptor molecules. We hypothesized that a toxin-neuropeptide conjugate would alter pain by first being taken up by specific receptors for the neuropeptide expressed on the neuronal cells. Then, once inside the cell the toxin would inhibit the neurons’ activity without killing the neurons, thereby providing pain relief without lesioning the nervous system. In an effort to inactivate the nociceptive neurons in the trigeminal nucleus caudalis in mice we targeted the NK1 receptor (NK1R) using substance P (SP). The catalytically active light chain of botulinum neurotoxin type A (LC/A) was conjugated with SP. Our results indicate that the conjugate BoNT/A-LC:SP is internalized in cultured NK1R expressing neurons and also cleaves the target of botulinum toxin, a component docking motif necessary for release of neurotransmitters called SNAP-25. The conjugate was next tested in a mouse model of Taxol induced neuropathic pain. An intracisternal injection of BoNT/A-LC:SP decreased thermal hyperalgesia as measured by the operant orofacial nociception assay. These findings indicate that conjugates of the light chain of botulinum toxin are extremely promising agents for use in suppressing neuronal activity for extended time periods and that BoNT/A-LC:SP may be a useful agent for treating chronic pain.

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“…This area expresses NK1R (23). To verify selective uptake of SP-LC/A, the cells were incubated with either BoNT/A-LC:SP (50 ng/ml) or BoNT/A-LC (50 ng/ml).…”

Section: Resultsmentioning

confidence: 99%

Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A

Mustafa

Anderson

Bokrand-Donatelli

et al. 2013

Pain

View full text Add to dashboard Cite

show abstract

“…Since we observed differences between genotypes and sexes during these acclimatization periods, we designed an experiment to analyze the stress response by studying the Hypothalamus-Pituitary-Adrenal axis (HPA) (Fig 1C). Restraint stress was carried out in a 50-ml ventilated conical tube for 60 min [26]. Floxed and muscle-IL6 KO 5–6 month-old male (n = 11/10) and female (9/10) mice were subjected to restraint stress.…”

Section: Methodsmentioning

confidence: 99%

Role of muscle IL-6 in gender-specific metabolism in mice

et al. 2017

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The aim of the present work was to further explore the physiological roles of muscle-derived IL-6. Adult-floxed and conditional skeletal muscle IL-6 knock out male and female mice were used to study energy expenditure (indirect calorimetry at rest and during treadmill exercise, and body temperature cycle during the light phase) and energy intake (response to fast/refeeding). We also evaluated the responses to leptin and the activity of the insulin signalling pathway in skeletal muscle and liver by phosphorylation of Akt at Ser 473. The stress response was also studied. Results indicate a relevant role of muscle IL-6 in maintaining energy homeostasis, especially in males. Absence of muscle IL-6 in male mice results in lower core body temperature in the light phase, increased respiratory exchange ratio (RER) both at rest and during exercise, increased expression of TCA cycle marked gene, citrate synthase in muscle, reduced fat storage and decreased body weight and food consumption in response to leptin. In females, muscle IL-6 deficiency increases VO2 and CO2 levels similarly. Also in contrast to males, energy expenditure (EE) measured over 48h reveals a significant elevation in female mice with muscle IL-6 deficiency; moreover, they show a modified response to fasting-refeeding and to restraint stress. The present results contribute to the understanding of the role of muscle IL-6 in male and female mouse metabolism, not only during exercise but also in the basal state and in situations where energy balance is altered.

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“…RST stress experiments were designed and conducted in line with previous reports [42]–[44]. Following the acclimation period, individual cages of animals were randomly assigned to control or RST groups.…”

Section: Methodsmentioning

confidence: 99%

Prolonged Restraint Stress Increases IL-6, Reduces IL-10, and Causes Persistent Depressive-Like Behavior That Is Reversed by Recombinant IL-10

et al. 2013

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Altered inflammatory cytokine profiles are often observed in individuals suffering from major depression. Recent clinical work reports on elevated IL-6 and decreased IL-10 in depression. Elevated IL-6 has served as a consistent biomarker of depression and IL-10 is proposed to influence depressive behavior through its ability to counterbalance pro-inflammatory cytokine expression. Clinical and animal studies suggest a role for IL-10 in modifying depressive behavior. Murine restraint stress (RST) is regularly employed in the study of behavioral and biological symptoms associated with depressive disorders. While responses to acute RST exposure have been widely characterized, few studies have examined the ongoing and longitudinal effects of extended RST and fewer still have examined the lasting impact during the post-stress period. Consistent with clinical data, we report that a protocol of prolonged murine RST produced altered cytokine profiles similar to those observed in major depressive disorder. Parallel to these changes in circulating cytokines, IL-10 mRNA expression was diminished in the cortex and hippocampus throughout the stress period and following cessation of RST. Moreover, chronic RST promoted depressive-like behavior throughout the 28-day stress period and these depressive-like complications were maintained weeks after cessation of RST. Because of the correlation between IL-10 suppression and depressive behavior and because many successful antidepressant therapies yield increases in IL-10, we examined the effects of IL-10 treatment on RST-induced behavioral changes. Behavioral deficits induced by RST were reversed by exogenous administration of recombinant IL-10. This work provides one of the first reports describing the biological and behavioral impact following prolonged RST and, taken together, this study provides details on the correlation between responses to chronic RST and those seen in depressive disorders.

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Adrenocortical and behavioural response to chronic restraint stress in neurokinin-1 receptor knockout mice

Cited by 13 publications

References 63 publications

Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A

Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A

Role of muscle IL-6 in gender-specific metabolism in mice

Prolonged Restraint Stress Increases IL-6, Reduces IL-10, and Causes Persistent Depressive-Like Behavior That Is Reversed by Recombinant IL-10

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