scholarly journals Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Steven F. Grieco ◽  
Xin Qiao ◽  
Kevin G. Johnston ◽  
Lujia Chen ◽  
Renetta R. Nelson ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Forced Swim Test ◽  
Inhibitory Neurons ◽  
Neuregulin 1 ◽  
Synaptic Excitation ◽  
Adult Mice ◽  
Antidepressant Effects ◽  
Erbb4 Receptor ◽  
Antidepressant Action

AbstractSubanesthetic ketamine evokes rapid antidepressant effects in human patients that persist long past ketamine’s chemical half-life of ~2 h. Ketamine’s sustained antidepressant action may be due to modulation of cortical plasticity. We find that ketamine ameliorates depression-like behavior in the forced swim test in adult mice, and this depends on parvalbumin-expressing (PV) neuron-directed neuregulin-1 (NRG1)/ErbB4 signaling. Ketamine rapidly downregulates NRG1 expression in PV inhibitory neurons in mouse medial prefrontal cortex (mPFC) following a single low-dose ketamine treatment. This NRG1 downregulation in PV neurons co-tracks with the decreases in synaptic inhibition to mPFC excitatory neurons for up to a week. This results from reduced synaptic excitation to PV neurons, and is blocked by exogenous NRG1 as well as by PV targeted ErbB4 receptor knockout. Thus, we conceptualize that ketamine’s effects are mediated through rapid and sustained cortical disinhibition via PV-specific NRG1 signaling. Our findings reveal a novel neural plasticity-based mechanism for ketamine’s acute and long-lasting antidepressant effects.

scholarly journals Interaction between perineuronal nets and ketamine in antidepressant action

2021 ◽  
Author(s):  
Calvin K Young ◽  
Kachina G Kinley ◽  
Neil McNaughton
Keyword(s):  
Suicide Risk ◽  
Forced Swim Test ◽  
Perineuronal Nets ◽  
Scaffolding Proteins ◽  
Infralimbic Cortex ◽  
Swim Test ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Action

Depression is highly prevalent, increases suicide risk, and is now the leading cause of disability worldwide. Our ability to treat depression is hampered by the lack of understanding of its biological underpinnings and of the mode of action of effective treatments. We hypothesised that the scaffolding proteins in the medial frontal cortex play a major role in effective antidepressant action. We implanted cannulae into the infralimbic cortex to inject chABC and locally remove perineuronal nets and then tested for antidepressant effects with the forced swim test. We further tested if systemic injections of ketamine had an additive effect. Our preliminary data indicate that neither the removal of these scaffolding proteins nor ketamine were sufficient to decrease depression-like behaviour, but may interact synergistically to decrease immobility time in the forced swim test.

scholarly journals Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

2020 ◽  
Author(s):  
Steven F. Grieco ◽  
Xin Qiao ◽  
Xiaoting Zheng ◽  
Yongjun Liu ◽  
Lujia Chen ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
List Type ◽  
Visual Cortical

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects

scholarly journals Contrasting roles for parvalbumin-expressing inhibitory neurons in two forms of adult visual cortical plasticity

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Eitan S Kaplan ◽  
Sam F Cooke ◽  
Robert W Komorowski ◽  
Alexander A Chubykin ◽  
Aurore Thomazeau ◽  
...  
Keyword(s):  
Visual Experience ◽  
Cortical Plasticity ◽  
Ocular Dominance ◽  
Critical Role ◽  
Monocular Deprivation ◽  
Inhibitory Neurons ◽  
Similar Increase ◽  
Adult Mice ◽  
Dependent Modification ◽  
Visual Cortical

The roles played by cortical inhibitory neurons in experience-dependent plasticity are not well understood. Here we evaluate the participation of parvalbumin-expressing (PV+) GABAergic neurons in two forms of experience-dependent modification of primary visual cortex (V1) in adult mice: ocular dominance (OD) plasticity resulting from monocular deprivation and stimulus-selective response potentiation (SRP) resulting from enriched visual experience. These two forms of plasticity are triggered by different events but lead to a similar increase in visual cortical response. Both also require the NMDA class of glutamate receptor (NMDAR). However, we find that PV+ inhibitory neurons in V1 play a critical role in the expression of SRP and its behavioral correlate of familiarity recognition, but not in the expression of OD plasticity. Furthermore, NMDARs expressed within PV+ cells, reversibly inhibited by the psychotomimetic drug ketamine, play a critical role in SRP, but not in the induction or expression of adult OD plasticity.

scholarly journals Antidepressant effects of valproic acid in an animal model of depression

2019 ◽  
Vol 66 (2) ◽  
pp. 1-3
Author(s):  
K. Buzgoova ◽  
L. Balagova ◽  
N. Hlavacova ◽  
D. Jezova
Keyword(s):  
Valproic Acid ◽  
Forced Swim Test ◽  
Antidepressant Drug ◽  
Mood Stabilizer ◽  
Behavioral Approach ◽  
Antidepressant Effect ◽  
Swim Test ◽  
Antidepressant Effects ◽  
Animal Model Of Depression ◽  
Antidepressant Action

Abstract Valproic acid, beside its anticonvulsant action, is widely used as a mood stabilizer in the therapy of bipolar disorder. The potential antidepressant action of valproic acid has not been sufficiently characterized so far. The aim of the present study was to evaluate the antidepressant effect of valproic acid in an aldosterone model of depression. Subchronic treatment with valproic acid resulted in a reduction of the time spent in immobility in the forced swim test. In conclusion, the present study provides evidence on antidepressant effects of valproic acid using a classical behavioral approach for testing the efficacy of antidepressant drug in animal models.

Adaptive and Maladaptive Neural Plasticity Due to Facial Nerve Palsy

2016 ◽  
Vol 224 (2) ◽  
pp. 102-111 ◽  
Author(s):  
Carsten M. Klingner ◽  
Stefan Brodoehl ◽  
Gerd F. Volk ◽  
Orlando Guntinas-Lichius ◽  
Otto W. Witte
Keyword(s):  
Facial Nerve ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Motor Nerve ◽  
Predictive Coding ◽  
Theoretical Framework ◽  
Cortical Reorganization ◽  
Nerve Lesion ◽  
Peripheral Facial Palsy

Abstract. This paper reviews adaptive and maladaptive mechanisms of cortical plasticity in patients suffering from peripheral facial palsy. As the peripheral facial nerve is a pure motor nerve, a facial nerve lesion is causing an exclusive deefferentation without deafferentation. We focus on the question of how the investigation of pure deefferentation adds to our current understanding of brain plasticity which derives from studies on learning and studies on brain lesions. The importance of efference and afference as drivers for cortical plasticity is discussed in addition to the crossmodal influence of different competitive sensory inputs. We make the attempt to integrate the experimental findings of the effects of pure deefferentation within the theoretical framework of cortical responses and predictive coding. We show that the available experimental data can be explained within this theoretical framework which also clarifies the necessity for maladaptive plasticity. Finally, we propose rehabilitation approaches for directing cortical reorganization in the appropriate direction and highlight some challenging questions that are yet unexplored in the field.

scholarly journals Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

2018 ◽  
Vol 33 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Jaclyn N Highland ◽  
Patrick J Morris ◽  
Panos Zanos ◽  
Jacqueline Lovett ◽  
Soumita Ghosh ◽  
...  
Keyword(s):  
Oral Administration ◽  
Learned Helplessness ◽  
Oral Bioavailability ◽  
Forced Swim Test ◽  
Abuse Potential ◽  
Absolute Bioavailability ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Efficacy

Background: ( R,S)-ketamine has gained attention for its rapid-acting antidepressant actions in patients with treatment-resistant depression. However, widespread use of ketamine is limited by its side effects, abuse potential, and poor oral bioavailability. The ketamine metabolite, ( 2R,6R)-hydroxynorketamine, exerts rapid antidepressant effects, without ketamine’s adverse effects and abuse potential, in rodents. Methods: We evaluated the oral bioavailability of ( 2R,6R)-hydroxynorketamine in three species (mice, rats, and dogs) and also evaluated five candidate prodrug modifications for their capacity to enhance the oral bioavailability of ( 2R,6R)-hydroxynorketamine in mice. Oral administration of ( 2R,6R)-hydroxynorketamine was assessed for adverse behavioral effects and for antidepressant efficacy in the mouse forced-swim and learned helplessness tests. Results: ( 2R,6R)-hydroxynorketamine had absolute bioavailability between 46–52% in mice, 42% in rats, and 58% in dogs. Compared to intraperitoneal injection in mice, the relative oral bioavailability of ( 2R,6R)-hydroxynorketamine was 62%, which was not improved by any of the candidate prodrugs tested. Following oral administration, ( 2R,6R)-hydroxynorketamine readily penetrated the brain, with brain to plasma ratios between 0.67–1.2 in mice and rats. Oral administration of ( 2R,6R)-hydroxynorketamine to mice did not alter locomotor activity or precipitate behaviors associated with discomfort, sickness, or stereotypy up to a dose of 450 mg/kg. Oral ( 2R,6R)-hydroxynorketamine reduced forced-swim test immobility time (15–150 mg/kg) and reversed learned helplessness (50–150 mg/kg) in mice. Conclusions: These results demonstrate that ( 2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy following oral administration in mice.

scholarly journals Effects of Daily Intake of Plant and Animal Oils on the Incidence of Depression in Adult Mice

2021 ◽  
Author(s):  
Hooman Teymourian ◽  
Farzad Ashrafi ◽  
Farnak Behnaz ◽  
Hamidreza Azizi Faresani ◽  
Fatemeh Rezaee-Tazangi ◽  
...  
Keyword(s):  
Olive Oil ◽  
Vegetable Oil ◽  
Forced Swim Test ◽  
Daily Intake ◽  
Frying Oil ◽  
Adult Mice ◽  
Significant Difference ◽  
Group A ◽  
Group 2 ◽  
Group D

Background: Depression is a complicated disturbance affected by a collection of biological and environmental factors. The first aim of psychiatric studies is to recognize biological markers that could be utilized to predict improvement and increase reactions to antidepressant treatments. Diet affects different aspects of health, including depression. The aim of study was to determine antidepressant-like effects of some consumable oils, the effects of oils on depression were compared. Methods: Thirty-two male and female mice (Mus musculus (BALB/c)) weighing 25- 35 g were randomly divided into 8 groups (4 mice in each group, 2 male and 2 female, A: Laden sunflower liquid oil, B: 50% vegetable oil + 50% olive oil, C: Kermanshah Rojin animal oil, D: Spring frying oil, E: Distilled water, F: BAHAR solid vegetable oil, G: Olive oil, H: 50% Kermanshah animal oil + 50% of olive oil). In different groups, 30 g of vegetable or animal oil was gavaged every day at 1:00 pm. Five types of vegetable and animal oils among the high consumption oils in the market were selected, including spring frying oil (used for several times in 305˚f, usually used in eastern Asia countries), Laden sunflower liquid oil, olive oil, Kermanshah Rojin animal oil, and BAHAR solid vegetable oil. After 6 weeks of using the oils diet, the forced swim test was utilized as a test of depression like behavior. Results: There was a significant difference between all groups (P < 0.0001). Based on the results, the latency time of immobility in group A significantly decreased in comparison with groups C (P ˂ 0.02), D (P ˂ 0.003), and G (P < 0.001). However, it increased in groups B and C compared to group H (P ˂ 0.02). Also, this parameter in group D increased significantly compared to groups E (P < 0.01), F (P < 0.05), and H (P < 0.002). Conclusion: The results indicated that olive oil had a preventive effect against forced swimming-induced depression-like symptoms.

scholarly journals Neuregulin 1 Regulates Proliferation of Leydig Cells to Support Spermatogenesis and Sexual Behavior in Adult Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4899-4913 ◽  
Author(s):  
Takashi Umehara ◽  
Ikko Kawashima ◽  
Tomoko Kawai ◽  
Yumi Hoshino ◽  
Ken-ichirou Morohashi ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Leydig Cells ◽  
Neuregulin 1 ◽  
Adult Mice

scholarly journals Recombinant Neuregulin 1 Does Not Activate Cardiomyocyte DNA Synthesis in Normal or Infarcted Adult Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115871 ◽  
Author(s):  
Sean Reuter ◽  
Mark H. Soonpaa ◽  
Anthony B. Firulli ◽  
Audrey N. Chang ◽  
Loren J. Field
Keyword(s):  
Dna Synthesis ◽  
Neuregulin 1 ◽  
Adult Mice

Does 5-hydroxytryptamine influence "purinergic" inhibitory neurons in the intestine?

1979 ◽  
Vol 237 (2) ◽  
pp. E198
Author(s):  
D L Vermillion ◽  
J P Gillespie ◽  
A R Cooke ◽  
J D Wood
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Contractile Response ◽  
Circular Muscle ◽  
Inhibitory Neurons ◽  
Relaxation Response ◽  
Taenia Coli ◽  
Synaptic Excitation ◽  
Small Intestinal ◽  
Neurotransmitter Substance

Intrinsic inhibitory neurons to guinea pig taenia coli and small bowel circular muscle were activated by transmural electrical stimulation, and the postinhibitory contractile response of the muscle was utilized to evaluate whether or not the neuronal action of 5-hydroxytryptamine (5HT) was associated with the inhibitory neurons. The postinhibitory contractile responses of the small intestinal circular muscle were unaffected by 5HT. The 5HT antagonist methysergide also did not affect the poststimulus contractile response of the circular muscle. The amplitude and area under the contractile curve of the poststimulus contractile response of the taenia coli were reduced and the amplitude of the relaxation response to electrical stimulation was increased in one-half of the preparations after application of 5HT. Methysergide did not alter the poststimulus contractile response of the taenia coli. 5HT is implicated as a neurotransmitter substance for slow synaptic excitation within the enteric nervous system of the guinea pig small intestine; however, the 5HT synapses do not appear to be present on the "purinergic" inhibitory neurons nor on neurons that synaptically influence the inhibitory neurons.

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