Estradiol regulation of hypothalamic astrocyte adenosine 5′-monophosphate-activated protein kinase activity: Role of hindbrain catecholamine signaling

Tamrakar, Pratistha; Briski, Karen P.

doi:10.1016/j.brainresbull.2014.12.002

Cited by 19 publications

(12 citation statements)

References 30 publications

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“…In addition, treatment with compound C, an AMPK α inhibitor, for 1 week reduced food intake, body weight, plasma leptin, and adiponectin levels [ 106 ]. Furthermore, estradiol also regulates AMPK activity in caudal hindbrain A2 noradrenergic neurons [ 107 ] and hypothalamic astrocyte pAMPK is augmented by hypoglycemia in the presence of estradiol [ 108 ]. In addition, there is a reduction of hypothalamic AMPK depending on estradiol levels in pregnant rats [ 109 ].…”

Section: The Inhibitorsmentioning

confidence: 99%

Hypothalamic AMPK as a Regulator of Energy Homeostasis

et al. 2016

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Activated in energy depletion conditions, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and regulator in both central nervous system and peripheral organs. Hypothalamic AMPK restores energy balance by promoting feeding behavior to increase energy intake, increasing glucose production, and reducing thermogenesis to decrease energy output. Besides energy state, many hormones have been shown to act in concert with AMPK to mediate their anorexigenic and orexigenic central effects as well as thermogenic influences. Here we explore the factors that affect hypothalamic AMPK activity and give the underlying mechanisms for the role of central AMPK in energy homeostasis together with the physiological effects of hypothalamic AMPK on energy balance restoration.

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Section: The Inhibitorsmentioning

confidence: 99%

Hypothalamic AMPK as a Regulator of Energy Homeostasis

et al. 2016

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“…In the present study, a small population of cells was unexpectedly observed to survive for >72 h in the absence of glucose. Previous studies have demonstrated that astrocytes present in primary hippocampal cultures possess glycogen stores that provide a buffer to alterations in glucose reserves (41,42). However, the hypothalamic model used in the present study consisted of immortalized hypothalamic neurons and no supporting cells.…”

Section: Discussionmentioning

confidence: 90%

Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells

Chakraborty

Cohen

Yohanan

et al. 2016

Molecular Medicine Reports

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Estrogen (E2) has been demonstrated to possess protective effects from hypoglycemic toxicity, particularly in the pancreas. In the central nervous system, several brain regions, such as the hypothalamus, are highly vulnerable to hypoglycemic injuries that may lead to seizures, coma, and mortality. The present study performed a novel in vitro assay of hypoglycemic injury to hypothalamic cells, and is the first study, to the best of our knowledge, to demonstrate that E2 protects hypothalamic cells from hypoglycemic toxicity. The toxic effects of hypoglycemia on hypothalamic cells in vitro was determined by performing cell counts, together with MTT and lactate dehydrogenase assays, using the N38 murine hypothalamic cell line. Following 24 and 48 h in hypoglycemic conditions, a 60 and 75% reduction in cell number and mitochondrial function was observed, which reached 80 and ~100% by 72 and 96 h, respectively. E2 treatment prevented the hypoglycemia‑induced loss in cell number and mitochondrial toxicity at 24 and 48 h. However at 72 and 96 h of hypoglycemic conditions, the neuroprotective effects of E2 on cell number or mitochondrial function was not significant or not present at all. In order to determine whether E2 exerted its effects through the AKT signaling pathway, the expression of proline‑rich AKT substrate of 40 kDa (PRAS40) was analyzed. No alterations in PRAS40 expression were observed when N38 cells were exposed to hypoglycemic shock. From the biochemical and molecular data obtained, the authors speculated that E2 exhibits neuroprotective effects against hypoglycemic shock in hypothalamic cells, which dissipates with time. Despite demonstrating no significant effect on total AKT/PRS40 activity, it is possible that E2 may mediate these neuroprotective effects by upregulating the phosphorylated‑AKT/pPRAS40 signaling pathway. The present study presented, to the best of our knowledge, the first in vitro model for hypoglycemic toxicity to hypothalamic cells, and provided evidence to suggest that E2 may protect hypothalamic cells from the damaging effects of hypoglycemia.

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“…More hypothalamic loci exhibited diminished pAMPK expression in OVX+E [PVH, VMH; LHA] versus OVX+O [PVH] in response to intra-CV4 Cc delivery, suggesting that estrogen may enhance hypothalamic sensor reactivity to and/or strength of hindbrain sensor-mediated input to those structures. Metabolo-sensory A2 noradrenergic neurons are a likely caudal hindbrain substrate for estrogenic control of hindbrain-hypothalamic AMPK connectivity, as these cells exhibit steroid-dependent adjustments in Fos expression in response to CV4 AICAR administration to OVX rats [Ibrahim et al, 2013] and are critical for hypoglycemia-associated increases in hypothalamic astrocyte AMPK activity in OVX+E animals [Tamrakar and Briski, 2015]. The latter work emphasizes the additional need to characterize the hypothalamic cell compartments (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…; 10 mm/100 g bw ) filled with the vehicle, safflower oil (O) or 30 μg estradiol benzoate (E)/mL oil [Briski et al, 2001]. This steroid replacement regimen yields approximate plasma E concentrations of 22 pg/mL [Tamrakar et al,2015], replicating circulating hormone levels characteristic of metestrus in 4-day [Butcher et al, 1974] or of diestrus day-2 in 5-day ovary-intact cycling animals [Goodman, 1978]. Ketoprofen (1 mg/kg bw sc ) was administered prior to and after each surgery; closed incisions were treated topically with 0.25% bupivicaine (1-3 drops).…”

Section: Methodsmentioning

confidence: 99%

Role of estradiol in intrinsic hindbrain AMPK regulation of hypothalamic AMPK, metabolic neuropeptide, and norepinephrine activity and food intake in the female rat

et al. 2016

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This study addressed the hypothesis that dorsomedial hindbrain adenosine 5’-monophosphate-activated protein kinase (AMPK) imposes inherent control over hypothalamic AMPK, neuropeptide, and norepinephrine (NE) activity and governs feeding in an estradiol-dependent manner. Groups of estradiol (E)- or oil (O)-implanted ovariectomized rats were injected with the AMPK inhibitor Compound C (Cc) or vehicle into the caudal fourth ventricle (CV4) prior to micropunch-dissection of individual hypothalamic metabolic loci or assessment of food intake. Cc decreased hindbrain dorsal vagal complex phosphoAMPK (pAMPK) profiles in both E and O; tissue ATP levels were reduced by this treatment in O only. In E/Cc, pAMPK expression was diminished in the lateral hypothalamic area (LHA) and ventromedial (VMH) and paraventricular (PVH) nuclei; only PVH pAMPK was suppressed by this treatment in O/Cc. Cc decreased PVH corticotropin-releasing hormone and arcuate (ARH) proopiomelanocortin (POMC) and neuropeptide Y in O, but suppressed only POMC in E. O/Cc exhibited both augmented (PVH, VMH) and decreased (LHA, ARH) hypothalamic NE content, whereas Cc treatment of E elevated preoptic and dorsomedial hypothalamic nucleus NE. Cc completely or incompletely repressed feeding in E versus O, respectively. Results implicate dorsomedial hindbrain AMPK in physiological stimulus-induced feeding in females. Excepting POMC, hypothalamic neuropeptide targets of input from that sensor may differ in presence vs. absence of estrogen. Estradiol likely determines hypothalamic targets of altered NE signaling due to hindbrain AMPK activation. Divergent changes in NE content of hypothalamic loci in O/Cc uniquely demonstrate sensor-induced bimodal catecholamine signaling to those sites.

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Estradiol regulation of hypothalamic astrocyte adenosine 5′-monophosphate-activated protein kinase activity: Role of hindbrain catecholamine signaling

Cited by 19 publications

References 30 publications

Hypothalamic AMPK as a Regulator of Energy Homeostasis

Hypothalamic AMPK as a Regulator of Energy Homeostasis

Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells

Role of estradiol in intrinsic hindbrain AMPK regulation of hypothalamic AMPK, metabolic neuropeptide, and norepinephrine activity and food intake in the female rat

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