
Christa J Van DortHarvard Medical School | HMS · Department of Anesthesia
Christa J Van Dort
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29
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Publications (29)
Introduction
Dexmedetomidine (dex) is an alpha 2A adrenergic receptor agonist that is used clinically as a sedative. Dex is thought to induce sedation via disinhibition of the preoptic area which is similar to what occurs during non-rapid eye movement (NREM) sleep induction. Human, cat and rat electroencephalogram (EEG) studies have shown similarit...
Objective:
Sleep disruption is frequently associated with type 2 diabetes (T2D) and hyperglycemia. We recently reported the effectiveness of a continuous care intervention (CCI) emphasizing nutritional ketosis for improving HbA1c, body weight and cardiovascular risk factors in T2D patients. The present study assessed the effect of this CCI approac...
The periaqueductal gray (PAG) is a significant modulator of both analgesic and fear behaviors in both humans and rodents, but the underlying circuitry responsible for these two phenotypes is incompletely understood. Importantly, it is not known if there is a way to produce analgesia without anxiety by targeting the PAG, as modulation of glutamate o...
Objective: Sleep disruption is frequently associated with type 2 diabetes (T2D) and hyperglycemia. We recently reported the effectiveness of a continuous care intervention (CCI) emphasizing nutritional ketosis for improving HbA1c, body weight and cardiovascular risk factors in T2D patients. The present study assessed the effect of this CCI approach...
Optogenetics and chemogenetics provide the ability to modulate neurons in a type- and region-specific manner. These powerful techniques are useful to test hypotheses regarding the neural circuit mechanisms of general anesthetic end points such as hypnosis and analgesia. With both techniques, a genetic strategy is used to target expression of light-...
Sudden unexpected death in epilepsy (SUDEP) is a devastating epilepsy complication. Seizure-induced respiratory arrest (S-IRA) occurs in many witnessed SUDEP patients and animal models as an initiating event leading to death. Thus, understanding the mechanisms underlying S-IRA will advance the development of preventive strategies against SUDEP. Ser...
Introduction
Many sedative and anesthetic drugs potentiate GABAA receptors in the brain, but their neuroanatomic sites of action are less clear. GABA neurons in the rostromedial tegmental nucleus (RMTg) of the ventral tegmental area (VTA) inhibit neighboring dopamine neurons that have been shown to promote wakefulness. Using bidirectional chemogene...
Significance
Although dopamine is known to promote wakefulness, the specific dopamine circuits in the brain that regulate arousal are not clear. Here we report that selective optogenetic stimulation of ventral tegmental area (VTA) dopamine neurons in mice produces a powerful arousal response sufficient to restore conscious behaviors, including the...
Background:
Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurot...
We thank Grace (1) for the opportunity to discuss the role of cholinergic neurons in rapid eye movement (REM) sleep further. Grace suggests that optogenetic activation of a population of neurons does not necessarily demonstrate their role in the endogenous system when interrogating complex neural circuitry. We agree that we do not prove necessity o...
Significance
Rapid eye movement (REM) sleep is a critical component of restful sleep, yet the mechanisms that control REM sleep are incompletely understood. Brainstem cholinergic neurons have been implicated in REM sleep regulation, but heterogeneous cell types in the area have made it difficult to determine the specific role of each population, le...
Placing a patient in a state of general anesthesia is crucial for safely and humanely performing most surgical and many nonsurgical procedures. How anesthetic drugs create the state of general anesthesia is considered a major mystery of modern medicine. Unconsciousness, induced by altered arousal and/or cognition, is perhaps the most fascinating be...
Methylphenidate or a D1 dopamine receptor agonist induces reanimation (active emergence) from general anesthesia. The authors tested whether electrical stimulation of dopaminergic nuclei also induces reanimation from general anesthesia.
In adult rats, a bipolar insulated stainless steel electrode was placed in the ventral tegmental area (VTA, n = 5...
A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia.
Using adult r...
Placing a patient in a state of general anesthesia is crucial for safely and humanely performing most surgical and many nonsurgical procedures. How anesthetic drugs create the state of general anesthesia is considered a major mystery of modern medicine. Unconsciousness, induced by altered arousal and/or cognition, is perhaps the most fascinating be...
During prolonged intervals of wakefulness, brain adenosine levels rise within the basal forebrain and cortex. The view that adenosine promotes sleep is supported by the corollary that N-methylated xanthines such as caffeine increase brain and behavioral arousal by blocking adenosine receptors. The four subtypes of adenosine receptors are distribute...
Vasopressin-activated calcium mobilizing receptor (VACM-1) is a member of the cullin gene family involved in ubiquitin-proteosome dependent regulation of cellular functions. Expression of VACM-1 cDNA in cos-1 cells in vitro decreases basal cAMP levels and inhibits growth. The expression of (S730A)VACM-1 mutant cDNA, which removes PKA-dependent phos...
Adenosine levels in the basal forebrain and cortex increase with prolonged wakefulness to promote sleep. Caffeine increases wakefulness by blocking adenosine receptors, yet the neurotransmitter systems and brain regions through which adenosine receptor blockade causes arousal are incompletely understood. The prefrontal cortex (PFC) contributes to t...
Vasopressin-activated calcium-mobilizing (VACM-1), a cul-5 gene, is localized on chromosome 11q22-23 close to the gene for Ataxia Telangiectasia in a region associated with a loss of heterozygosity in breast cancer tumor samples. To examine the biological role of VACM-1, we studied the effect of VACM-1 expression on cellular growth and gene express...
Vasopressin-activated Ca2+-mobilizing (VACM)-1 gene product is a 780-amino acid membrane protein that shares sequence homology with cullins, a family of genes involved in the regulation of cell cycle. However, when expressed in vitro, VACM-1 attenuates basal and vasopressin- and forskolin-induced cAMP production. Mutating the PKA-dependent phosphor...