Expression of ?2A adrenoceptors during rat neocortical development

Winzer‐Serhan, Ursula H.; Leslie, Frances M.

doi:10.1002/(sici)1097-4695(19990205)38:2<259::aid-neu8>3.0.co;2-u

Cited by 45 publications

(30 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During the first week of postnatal development, the expression of ␣ 2A receptor mRNA and protein changes markedly, giving rise to a more mature pattern of anatomical distribution. The temporal and spatial distribution of ␣ 2A -adrenoceptors in developing neocortex is consistent with expression of functional pro-DEVELOPMENTAL TOXICITY OF PSYCHOTHERAPEUTIC DRUGS teins on migrating and differentiating layer IV to II neurons, suggesting that these receptors may mediate a neurotrophic effect of NE during fetal cortical development (Winzer-Serhan and Leslie, 1999). ␣ 2B Receptor mRNA is transiently expressed in the developing vascular plexus during the time of neovascularization in the brain.…”

Section: Cortical [supporting

confidence: 55%

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

2004

View full text Add to dashboard Cite

Section: Cortical [supporting

confidence: 55%

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

2004

View full text Add to dashboard Cite

“…Specifically, ketamine induces anesthesia by blocking the glutamate N-methyl-D-aspartate (NMDA) receptors (Franks and Lieb, 1994) while isoflurane exerts its effect by potentiating γ-amino butyric-acid type A (GABA A ) receptors (Franks and Lieb, 1994), and inhibits receptor activity in the NMDA glutamate receptor subtypes (Shelton and Nicholson, 2010;Brosnan, 2011). Dexmedetomidine is a selective α2 adrenoceptor agonist at low (pharmacologic) doses and α2 adrenoceptors are believe to play an important role in cellular signaling in the central nervous system early in life (Song et al, 2004;Winzer-Serhan and Leslie, 1999).…”

Section: Discussionmentioning

confidence: 99%

Neurotoxic effects of dexmedetomidine in fetal cynomolgus monkey brains

Koo¹,

Oshodi²,

Meschter³

et al. 2014

J. Toxicol. Sci.

View full text Add to dashboard Cite

-The neuroprotective effects of dexmedetomidine have been reported by many investigators; however its underlying mechanism to reduce neuronal injury during a prolonged anesthesia remains unclear. In this study, we investigated the neurotoxic effects of dexmedetomidine in fetal monkey brains. In the present study, we compare the neurotoxic effects of dexmedetomidine and ketamine, a general anesthetic with a different mechanism of action, in fetal cynomolgus monkeys. Twenty pregnant monkeys at approximate gestation day 120 were divided into 4 groups: non-treatment controls (Group 1); ketamine at 20 mg/kg intramuscularly followed by a 12-hr infusion at 20-50 mg/kg/hr (Group 2); dexmedetomidine at 3 μg/kg intravenously (i.v.) over 10 min followed by a 12-hr infusion at the human equivalent dose (HED) of 3 μg/kg/hr (Group 3); and dexmedetomidine at 30 μg/kg i.v. over 10 min followed by a 12-hr infusion at 30 μg/kg/hr, 10 times HED (Group 4). Blood samples from both dams and fetuses were measured for concentration of dexmedetomidine. Each fetus was perfusion-fixed, serial sections were cut through the frontal cortex, and stained to detect for apoptosis (activated caspase 3 and TUNEL) and neurodegeneration (silver stain). In utero treatment with ketamine resulted in marked apoptosis and degeneration primarily in layers I and II of the frontal cortex. In contrast, fetal brains from animals treated with dexmedetomidine showed none to minimal neuroapoptotic or neurodegenerative lesions at both low-and high-dose treatments. Plasma levels confirmed systemic exposure of dexmedetomidine in both dams and fetuses. In conclusion, these results demonstrate that dexmedetomidine at both low-dose (HED) and highdose (10 times HED) does not induce apoptosis in the frontal cortex (layers I, II, and III) of developing brain of cynomolgus monkeys.

show abstract

“…For electrophysiology experiments, male Sprague-Dawley rats (Taconic Farms Germantown, NY) initially weighing 50-75g were used because brain slice viability is much improved in the juvenile compared to adult rodent brain (Alger et al, 1984; Gibb and Edwards, 1994). However, cortical CB1 and α2-adrenergic receptors (α2-AR) are fully functional by this age in rats (Berrendero et al, 1998; Winzer-Serhan and Leslie, 1999). Animals were housed 2-3 per cage on a 12 hour light:dark schedule in a temperature-controlled (25°C) colony room.…”

Section: Methodsmentioning

confidence: 99%

Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure

Reyes

Szot

Sikkema

et al. 2012

Experimental Neurology

View full text Add to dashboard Cite

The cannabinoid receptor agonist, WIN 55,212-2, increases extracellular norepinephrine levels in the rat frontal cortex under basal conditions, likely via desensitization of inhibitory α2-adrenergic receptors located on norepinephrine terminals. Here, the effect of WIN 55,212-2 on stress-induced norepinephrine release was assessed in the medial prefrontal cortex (mPFC), in adult male Sprague-Dawley rats using in vivo microdialysis. Systemic administration of WIN 55,212-2 thirty minutes prior to stressor exposure prevented stress-induced cortical norepinephrine release induced by a single exposure to swim when compared to vehicle. To further probe cortical cannabinoid-adrenergic interactions, postsynaptic α2-adrenergic receptor (AR)-mediated responses were assessed in mPFC pyramidal neurons using electrophysiological analysis in an in vitro cortical slice preparation. We confirm prior studies showing that clonidine increases cortical pyramidal cell excitability and that this was unaffected by exposure to acute stress. WIN 55,212-2, via bath application, blocked postsynaptic α2-AR mediated responses in cortical neurons irrespective of exposure to stress. Interestingly, stress exposure prevented the desensitization of α2-AR mediated responses produced by a history of cannabinoid exposure. Together, these data indicate the stress-dependent nature of cannabinoid interactions via both pre- and postsynaptic ARs. In summary, microdialysis data indicate that cannabinoids restrain stress-induced cortical NE efflux. Electrophysiology data indicate that cannabinoids also restrain cortical cell excitability under basal conditions; however, stress interferes with these CB1-α2 AR interactions, potentially contributing to over-activation of pyramidal neurons in mPFC. Overall, cannabinoids are protective of the NE system and cortical excitability but stress can derail this protective effect, potentially contributing to stress-related psychopathology. These data add to the growing evidence of complex, stress-dependent modulation of monoaminergic systems by cannabinoids and support the potential use of cannabinoids in the treatment of stress-induced noradrenergic dysfunction.

show abstract

Expression of ?2A adrenoceptors during rat neocortical development

Cited by 45 publications

References 48 publications

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

Neurotoxic effects of dexmedetomidine in fetal cynomolgus monkey brains

Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure

Contact Info

Product

Resources

About