Biology subjects

Rantamaki, T.

Publications and source records attributed to Rantamaki, T..

4 recordsLinked to original sources

bioRxiv2024

Anesthetic-like effects of ketamine in C. elegans

Transparency of C. elegans enables microscopic in vivo imaging of cellular processes, but immobilization is required due to high locomotor activity. Preservative NaN3 is commonly used for this, but is associated with oxidative stress and toxicity. Here, anesthetic-like effects of dissociate anesthetic ketamine in C. elegans are presented using video recordings and infrared-based automated activity tracking. Ketamine caused a reversible blockade of locomotion at a similar concentration (20-50 mM) at which NaN3 produces paralysis. Moreover, the recovery rate was remarkably high, and short-term ketamine treatment did not show signs of SKN-1 activation, a marker of the stress response.

pharmacology and toxicology↗

bioRxiv2021

Physiological basis underlying antidepressant-induced activation of TrkB receptors

We show that both pharmacological and non-pharmacological treatments of depression activate TrkB receptors--a well-established target of antidepressants--by inducing a physiological response coupled to sedation. Several rapid-acting antidepressants trigger TrkB signaling by evoking a state associated with electroencephalographic slow-wave activity, behavioral immobility, reduced cerebral glucose utilization, and lowered body temperature. Remarkably, antidepressant-induced TrkB signaling was not compromised in animals exhibiting reduced activity-dependent release of BDNF but was diminished by maintaining animals in warm ambient temperature. Most importantly, prevention of the hypothermic response attenuated the behavioral effects produced by rapid-acting antidepressant nitrous oxide. Our results suggest that the phenomenon underlying TrkB transactivation--changes in energy expenditure and thermoregulation--is essential, but not sufficient, for antidepressant responses. Indeed, regardless of differential clinical and pharmacodynamic properties, all drugs that disrupt energy metabolism and induce hypothermia activated TrkB. This study challenges pharmacology-centric hypotheses regarding antidepressant effects and highlight the role of complex changes in bioenergetics and thermoregulation. HighlightsO_LIRapid-acting antidepressants evoke homeostatic emergence of slow-wave sleep during which TrkB signaling becomes regulated. C_LIO_LINon-antidepressant metabolic inhibitors and diverse sedatives activate TrkB signaling. C_LIO_LIReduction in body temperature determined the ability of antidepressants to transactivate TrkB. C_LIO_LIDrug-induced TrkB signaling was blunted by maintenance of normothermic body temperature. C_LIO_LIWarm ambient temperature after nitrous oxide exposure blocked the antidepressant-like effects. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/458151v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1f7351borg.highwire.dtl.DTLVardef@bf920forg.highwire.dtl.DTLVardef@10e34eaorg.highwire.dtl.DTLVardef@1b42bb6_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors

Backgroundadministration of anandamide (AEA) or 2-arachidonoylglycerol (2AG) induces CB1 coupling and activation of TRKB receptors, regulating the neuronal migration and maturation in the developing cortex. However, at higher concentrations AEA also engages vanilloid receptor - TRPV1, usually with opposed consequences on behavior. Methods and ResultsUsing primary cell cultures from the cortex of rat embryos (E18) we determined the effects of AEA on phosphorylated TRKB (pTRK). We observed that AEA (at 100 and 200nM) induced a significant increase in pTRK levels. Such effect of AEA at 100nM was blocked by pretreatment with the CB1 antagonist AM251 (200nM) and, at the higher concentration of 200nM by the TRPV1 antagonist capsazepine (200nM), but mildly attenuated by AM251. Interestingly, the effect of AEA or capsaicin (a TRPV1 agonist, also at 200nM) on pTRK was blocked by TRKB.Fc (a soluble form of TRKB able to bind BDNF) or capsazepine, suggesting a mechanism dependent on BDNF release. Using the marble-burying test (MBT) in mice, we observed that the local administration of ACEA (a CB1 agonist) into the prelimbic region of prefrontal cortex (PL-PFC) was sufficient to reduce the burying behavior, while capsaicin or BDNF exerted the opposite effect, increasing the number of buried marbles. In addition, both ACEA and capsaicin effects were blocked by previous administration of k252a (an antagonist of TRK receptors) into PL-PFC. The effect of systemically injected CB1 agonist WIN55,212-2 was blocked by previous administration of k252a. We also observed a partial colocalization of CB1 /TRPV1 /TRKB in the PL-PFC, and the localization of TRPV1 in CaMK2+ cells. Conclusiontaken together, our data indicate that anandamide engages a coordinated activation of TRKB, via CB1 and TRPV1. Thus, acting upon CB1 and TRPV1, AEA could regulate the TRKB-dependent plasticity in both pre- and postsynaptic compartments.

neuroscience↗

bioRxiv2016

TrkB signaling underlies the rapid antidepressant effects of isoflurane

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3{beta} (GSK3{beta}). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.

neuroscience↗