Differential Effects of Estradiol on Encoding Properties of TMJ Units in Laminae I and V at the Spinomedullary Junction in Female Rats

2007 ◽  
Vol 98 (6) ◽  
pp. 3242-3253 ◽  
Author(s):  
A. Tashiro ◽  
K. Okamoto ◽  
S. B. Milam ◽  
D. A. Bereiter

To determine whether estrogen status modulated dorsal horn neural activity relevant to temporomandibular joint (TMJ) processing single units were recorded in superficial and deep laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C1–2) junction of ovariectomized (OvX) female rats under barbiturate anesthesia after 17β-estradiol (E2) treatment for 2 days. E2 dose-dependently enhanced the response to intra-TMJ stimulation by adenosine triphosphate (ATP) of neurons classified as nociceptive specific (NS), but not wide dynamic range (WDR), in superficial laminae. ATP caused similar responses among NS and WDR neurons from deep laminae in all groups. By contrast, the cutaneous receptive field areas of WDR, but not NS, units in superficial and deep laminae were enlarged in high E2-treated (HE2) compared with low E2-treated (LE2) females. Units from untreated or vehicle-treated male rats displayed responses similar to those of LE2 females. TMJ units in superficial laminae from females were more likely to receive convergent cutaneous input and respond to jaw movement than males, independent of E2 treatment. Western blot analysis revealed similar levels of P2X2 and P2X3 receptor protein in Vc/C1–2 or trigeminal ganglion samples in all groups. Immunohistochemistry revealed dense terminal labeling for P2X3 receptors in superficial laminae and moderate labeling in deep laminae at the Vc/C1–2 junction. These data indicated a significant linkage between estrogen status and the magnitude of articular input evoked by ATP from TMJ neurons in the superficial laminae at the Vc/C1–2 junction, whereas estrogenic modulation of TMJ neurons in deep laminae affected only the convergent input from overlying facial skin.

2003 ◽  
Vol 89 (3) ◽  
pp. 1467-1477 ◽  
Author(s):  
K. Okamoto ◽  
H. Hirata ◽  
S. Takeshita ◽  
D. A. Bereiter

Neurons responsive to stimulation of the temporomandibular joint (TMJ) region were recorded from superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C2) junction region of cycling female rats under barbiturate anesthesia. To determine if receptive field (RF) properties or sensitivity to algesic chemicals of TMJ units vary over the estrous cycle, animals were selected from proestrous (high estrogen) or early diestrous (low estrogen) stages. More than 90% of TMJ units from each group received convergent nociceptive input [wide dynamic range (WDR) or nociceptive specific (NS)-like] from facial skin. The cutaneous high-threshold RF areas of WDR units from proestrous rats were 30% larger than diestrous units, while RF areas of NS units were similar. Bradykinin (BK, 0.1–10 μM) injection into the TMJ region excited a high percentage of units (>80% of total) from both groups in a dose-related manner. However, BK-evoked response magnitude ( R mag, +140%) and duration (+64%) were greater for proestrous than diestrous units. Both WDR and NS-like TMJ units of proestrous females displayed enhanced BK-evoked R mag values and response duration. Glutamate or mustard oil excitation of TMJ units was not affected by stage of the estrous cycle. Several TMJ units from proestrous and diestrous females were activated antidromically from the contralateral posterior thalamus, indicating that projection and nonprojection units were included in the sample population. These results were consistent with the hypothesis that factors related to stage of the estrous cycle modify the processing of deep craniofacial inputs by superficial dorsal horn neurons at the spinomedullary junction, a key region for the initial integration of sensory signals from the TMJ.


2001 ◽  
Vol 86 (5) ◽  
pp. 2393-2404 ◽  
Author(s):  
S. Takeshita ◽  
H. Hirata ◽  
D. A. Bereiter

Temporomandibular disorders (TMD) represent a family of recurrent conditions that often cause pain in the temporomandibular joint (TMJ) region and muscles of mastication. To determine if TMJ-responsive neurons encoded the intensity of pro-inflammatory chemical signals, dose-effect relationships were assessed after direct injection bradykinin into the joint space and compared with responses after injection of glutamate or saline. Neurons were recorded from superficial laminae of the trigeminal subnucleus caudalis/upper cervical cord junction region (Vc/C2) and identified by palpation of the TMJ region in barbiturate-anesthetized male rats. The majority (62 of 84) of units received convergent input from facial skin, while 26% were driven only by deep input from the TMJ region. Conduction-velocity based on the latency to firing after electrical stimulation of the TMJ region indicated 64% of units were driven by A-delta fiber input only. Bradykinin (0.1–10 μM) excited 69% of neurons tested, and 70% (19 of 27) of these units were activated by the lowest dose (0.1 μM). Glutamate (50–200 mM) excited 27% of units; however, when tested after bradykinin, 58% of units were activated by glutamate. Some TMJ units (17%) were excited by saline injection alone and not enhanced further by bradykinin or glutamate. Most (88%) TMJ units were activated by injection of the small fiber excitant, mustard oil (20% solution), into the TMJ region. Units responsive to bradykinin or glutamate were not restricted to particular classes [e.g., wide dynamic range (WDR), nociceptive specific (NS), deep only]. A small percentage of TMJ units (∼15%) were activated antidromically from the contralateral posterior thalamus. In parallel studies using c- fos immunocytochemistry, bradykinin (1 μM) injection into the TMJ region produced a greater number of Fos-positive neurons at the Vc/C2 region than glutamate (200 mM) or saline. These results revealed two broad classes of TMJ units that encoded the intensity of pro-inflammatory chemical stimuli applied to the TMJ region, units that received convergent nociceptive input from facial skin (i.e., WDR and NS units) and units that responded only to deep input from the TMJ region. On the basis of encoding properties and efferent projection status, it is concluded that activation of TMJ units within the superficial laminae at the Vc/C2region contribute to the diffuse and spreading nature of TMD pain sensation.


1999 ◽  
Vol 82 (5) ◽  
pp. 2092-2107 ◽  
Author(s):  
Harumitsu Hirata ◽  
James W. Hu ◽  
David A. Bereiter

Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO2 pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO2 stimulation. The evoked activity of most cells occurred at 60% CO2 after a delay of 7–22 s. At the Vi/Vc transition three response patterns were seen. Type I cells ( n = 11) displayed an increase in activity with increasing CO2 concentration. Type II cells ( n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO2 concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO2 pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO2-responsive cells ( n = 15) displayed an increase in firing rates with greater CO2 concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO2 pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5–3.5 mg/kg iv) enhanced the CO2-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO2 stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways.


2020 ◽  
Author(s):  
Dannia Islas-Preciado ◽  
Steven R. Wainwright ◽  
Julia Sniegocki ◽  
Stephane E. Lieblich ◽  
Shunya Yagi ◽  
...  

AbstractDecision-making is a complex process essential to daily adaptation in many species. Risk is an inherent aspect of decision-making and it is influenced by gonadal hormones. Testosterone and 17β-estradiol may modulate decision making and impact the mesocorticolimbic dopamine pathway. Here, we explored sex differences, the effect of gonadal hormones and the dopamine agonist amphetamine on risk-based decision making. Intact or gonadectomised (GDX) male and female rats underwent to a probabilistic discounting task. High and low doses of testosterone propionate (1.0 or 0.2 mg) and 17β-estradiol benzoate (0.3 μg) were administered to assess acute effects on risk-based decision making. After 3-days of washout period, intact and GDX rats received high or low (0.5 or 0.125 mg/kg) doses of amphetamine and re-tested in the probabilistic discounting task. Under baseline conditions, males made more risky choices during probability discounting compared to female rats, particularly in the lower probability blocks, but GDX did not influence risky choice. The high, but not the low dose, of testosterone modestly reduced risky decision making in GDX male rats. Conversely, 17β-estradiol had no significant effect on risky choice regardless of GDX status in either sex. Lastly, a higher dose of amphetamine increased risky decision making in both intact males and females, but had no effect in GDX rats. These findings demonstrated sex differences in risk-based decision making, with males showing a stronger bias towards larger, uncertain rewards. GDX status influenced the effects of amphetamine, suggesting different dopaminergic regulation in risk-based choices among males and females.


1998 ◽  
Vol 80 (4) ◽  
pp. 2210-2214 ◽  
Author(s):  
Kai-Ming Zhang ◽  
Xiao-Min Wang ◽  
Angela M. Peterson ◽  
Wen-Yan Chen ◽  
Sukhbir S. Mokha

Kai-Ming Zhang, Xiao-Min Wang, Angela M. Peterson, Wen-Yan Chen, and Sukhbir S. Mokha. α2-Adrenoceptors modulate NMDA-evoked responses of neurons in the superficial and deeper dorsal horn of the medulla. J. Neurophysiol. 80: 2210–2214, 1998. Extracellular single unit recordings were made from neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in 21 male rats anesthetized with urethan. NMDA produced an antagonist-reversible excitation of 46 nociceptive as well as nonnociceptive neurons. Microiontophoretic application of a preferential α2-adrenoceptor (α2AR) agonist, (2-[2,6-dichloroaniline]-2-imidazoline) hydrochloride (clonidine), reduced the NMDA-evoked responses of 86% (6/7) of nociceptive-specific (NS) neurons, 82% (9/11) of wide dynamic range (WDR) neurons, and 67% (4/6) of low-threshold (LT) neurons in the superficial dorsal horn. In the deeper dorsal horn, clonidine inhibited the NMDA-evoked responses of 94% (16/17) of NS and WDR neurons and 60% (3/5) of LT neurons. Clonidine facilitated the NMDA-evoked responses in 14% (1/17) of NS, 9% (1/11) of WDR, and 33% (2/6) of LT neurons in the superficial dorsal horn. Idazoxan, an α2AR antagonist, reversed the inhibitory effect of clonidine in 90% (9/10) of neurons, whereas prazosin, an α1-adrenoceptor antagonist with affinity for α2BAR, and α2CAR, were ineffective. We suggest that activation of α2ARs produces a predominantly inhibitory modulation of the NMDA-evoked responses of nociceptive neurons in the medullary dorsal horn.


2000 ◽  
Vol 84 (4) ◽  
pp. 2078-2112 ◽  
Author(s):  
Amy Malick ◽  
Rew M. Strassman ◽  
Rami Burstein

Sensory information that arises in orofacial organs facilitates exploratory, ingestive, and defensive behaviors that are essential to overall fitness and survival. Because the hypothalamus plays an important role in the execution of these behaviors, sensory signals conveyed by the trigeminal nerve must be available to this brain structure. Recent anatomical studies have shown that a large number of neurons in the upper cervical spinal cord and caudal medulla project directly to the hypothalamus. The goal of the present study was to identify the types of information that these neurons carry to the hypothalamus and to map the route of their ascending axonal projections. Single-unit recording and antidromic microstimulation techniques were used to identify 81 hypothalamic-projecting neurons in the caudal medulla and upper cervical (C1) spinal cord that exhibited trigeminal receptive fields. Of the 72 neurons whose locations were identified, 54 were in laminae I–V of the dorsal horn at the level of C1 ( n = 22) or nucleus caudalis (Vc, n = 32) and were considered trigeminohypothalamic tract (THT) neurons because these regions are within the main projection territory of trigeminal primary afferent fibers. The remaining 18 neurons were in the adjacent lateral reticular formation (LRF) and were considered reticulohypothalamic tract (RHT) neurons. The receptive fields of THT neurons were restricted to the innervation territory of the trigeminal nerve and included the tongue and lips, cornea, intracranial dura, and vibrissae. Based on their responses to mechanical stimulation of cutaneous or intraoral receptive fields, the majority of THT neurons were classified as nociceptive (38% high-threshold, HT, 42% wide-dynamic-range, WDR), but in comparison to the spinohypothalamic tract (SHT), a relatively high percentage of low-threshold (LT) neurons were also found (20%). Responses to thermal stimuli were found more commonly in WDR than in HT neurons: 75% of HT and 93% of WDR neurons responded to heat, while 16% of HT and 54% of WDR neurons responded to cold. These neurons responded primarily to noxious intensities of thermal stimulation. In contrast, all LT neurons responded to innocuous and noxious intensities of both heat and cold stimuli, a phenomenon that has not been described for other populations of mechanoreceptive LT neurons at spinal or trigeminal levels. In contrast to THT neurons, RHT neurons exhibited large and complex receptive fields, which extended over both orofacial (“trigeminal”) and extracephalic (“non-trigeminal”) skin areas. Their responses to stimulation of trigeminal receptive fields were greater than their responses to stimulation of non-trigeminal receptive fields, and their responses to innocuous stimuli were induced only when applied to trigeminal receptive fields. As described for SHT axons, the axons of THT and RHT neurons ascended through the contralateral brain stem to the supraoptic decussation (SOD) in the lateral hypothalamus; 57% of them then crossed the midline to reach the ipsilateral hypothalamus. Collateral projections were found in the superior colliculus, substantia nigra, red nucleus, anterior pretectal nucleus, and in the lateral, perifornical, dorsomedial, suprachiasmatic, and supraoptic hypothalamic nuclei. Additional projections (which have not been described previously for SHT neurons) were found rostral to the hypothalamus in the caudate-putamen, globus pallidus, and substantia innominata. The findings that nonnociceptive signals reach the hypothalamus primarily through the direct THT route, whereas nociceptive signals reach the hypothalamus through both the direct THT and the indirect RHT routes suggest that highly prioritized painful signals are transferred in parallel channels to ensure that this critical information reaches the hypothalamus, a brain area that regulates homeostasis and other humoral responses required for the survival of the organism.


2018 ◽  
Vol 315 (5) ◽  
pp. H1159-H1173 ◽  
Author(s):  
Fatimah Najjar ◽  
Monir Ahmad ◽  
Diane Lagace ◽  
Frans H. H. Leenen

Patients with heart failure (HF) have a high prevalence of depression associated with a worse prognosis, particularly in older women. The present study evaluated whether sex and estrogens affect depression-like behavior and associated neuroinflammation induced by myocardial infarction (MI) in rats. MI was induced by occlusion of the left anterior descending artery in young adult male and female Wistar rats or in ovariectomized (OVX) female rats without and with estrogen [17β-estradiol (E2)] replacement. MI groups showed a comparable degree of cardiac dysfunction. Eight weeks post-MI, male rats with HF exhibited depression-like behaviors, including anhedonia and higher immobility in the sucrose preference and forced swim tests, which were not observed in female rats with HF. In the cued fear conditioning test, male but not female rats with HF froze more than sham rats. After OVX, female sham rats developed mild depression-like behaviors that were pronounced in OVX female rats post-MI and were largely prevented by E2 replacement. Cytokine levels in the plasma and paraventricular nucleus increased in both sexes with HF, but only male rats with HF showed an increase in cytokine levels in the prefrontal cortex. OVX alone did not affect cytokine levels, but OVX-MI caused significant increases in the prefrontal cortex, which were shifted to an anti-inflammatory pattern by E2 replacement. These results suggest that estrogens prevent depression-like behavior induced by HF post-MI in young adult female rats by inhibiting proinflammatory cytokine production and actions in the prefrontal cortex. NEW & NOTEWORTHY In contrast to male rats, female rats with heart failure after myocardial infarction do not develop depression-like behavior or increases in prefrontal cortex cytokines. However, after ovariectomy, female rats exhibit similar changes, which are prevented by 17β-estradiol replacement. Neuroinflammation in the prefrontal cortex in male subjects may contribute to depression-like behavior, whereas its estrogen-dependent absence in female subjects may protect against depression. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/sex-differences-in-depression-like-behavior-post-myocardial-infarction/ .


2005 ◽  
Vol 103 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Takehiro Nakamura ◽  
Ya Hua ◽  
Richard F. Keep ◽  
Jung-Weon Park ◽  
Guohua Xi ◽  
...  

Object The aims of this study were to determine the following: whether there are sex differences in intracerebral hemorrhage (ICH) induced brain injury in rats, whether delayed administration of 17β-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent. Methods Male and female Sprague—Dawley rats received an infusion of 100 µl autologous whole blood into the right basal ganglia. Twenty-four hours later the rats were killed. The effects of 17β-estradiol on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Both ER-α and hemeoxygenase (HO)-1 were investigated through Western blot and immunohistochemical analysis. Brain edema was significantly less severe in female compared with that in male rats. The ER antagonist ICI 182,780 exacerbated ICH-induced brain edema in female but not in male rats, indicating that ER-α activation during ICH is protective in female rats. Administration of exogenous 17β-estradiol in male, but not in female, rats significantly attenuated brain edema, neurological deficits, and ICH-induced changes in HO-1 when given 2 hours after hemorrhage. The effects of exogenous 17β-estradiol occurred through an ER-independent mechanism. Conclusions Results in this study indicate that 17β-estradiol could be a potential therapeutic agent for ICH.


2012 ◽  
Vol 302 (3) ◽  
pp. G365-G374 ◽  
Author(s):  
Janne Lebeck ◽  
Patrizia Gena ◽  
Heidi O'Neill ◽  
Mariusz T. Skowronski ◽  
Sten Lund ◽  
...  

In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown sex-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the present study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged with starvation in male rats, whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats compared with starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α-agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a sex-specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.


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