Neuronal and glial response in the rat hypothalamus–neurohypophysis complex with streptozotocin-induced diabetes

Luo, Yue; Kaur, Charanjit; Ling, Eng-Ang

doi:10.1016/s0006-8993(01)03258-9

Cited by 50 publications

(38 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…hypothalamic inflammation has been less well studied in T1D, it has been seen in STZ-induced T1D rats and is accompanied by both microglia and astrocyte activation, and neuronal degeneration (38,45,46).…”

Section: E694mentioning

confidence: 99%

“…HYPO neurons in diabetic animals can undergo degeneration (46), showing distension of rough endoplasmic reticulum, swollen mitochondria, and enhanced electron density of their cytoplasm (17). Neurons in the diabetic HYPO show increased arginine, oxytocin, N-methyl-D-aspartate receptor 1, neuronal nitric oxide synthase (NOS), and vasopressin expression but downregulated expression of GluR2/3 (20,46). Both hyperglycemia and hyperosmolality trigger increased neuronal activity (38).…”

Section: /Cd39mentioning

confidence: 99%

“…Neurons, microglia, and astrocytes constitute the major cellular elements in the HYPO, and activation of these cells is observed along with neuronal degeneration in T1D rats (38,46). IGF-I and IGF-binding protein-3 (IGFBP-3) comprise critical components of the IGF system that regulate key aspects of cell growth, motility, differentiation, and survival in both normal and pathological conditions.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice

Thinschmidt

Caballero

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Hu P, Thinschmidt JS, Caballero S, Adamson S, Cole L, Chan-Ling T, Grant MB. Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice. Am J Physiol Endocrinol Metab 308: E688 -E698, 2015. First published February 24, 2015 doi:10.1152/ajpendo.00504.2014.-Neuroinflammation and neurodegeneration have been observed in the brain in type 1 diabetes (T1D). However, little is known about the mediators of these effects. In T1D mice with 12-and 35-wk duration of diabetes we examined two mechanisms of neurodegeneration, loss of the neuroprotective factors insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and changes in indoleamine 2,3-dioxygenase (IDO) expression in the brain, and compared the response to age-matched controls. Furthermore, levels of matrix metalloproteinase-2 (MMP-2), nucleoside triphosphate diphosphohydrolase-1 (CD39), and ionized calcium-binding adaptor molecule 1 (Iba-1) were utilized to assess inflammatory changes in astrocytes, microglia, and blood vessels. In the diabetic hypothalamus (HYPO), we observed 20% reduction in neuronal soma diameter (P Ͻ 0.05) and reduced neuronal expression of IGFBP-3 (Ϫ32%, P Ͻ 0.05) and IGF-I (Ϫ15%, P Ͻ 0.05) compared with controls at 35 wk. In diabetic HYPO, MMP-2 expression was increased in astrocytes (46%, P Ͻ 0.01), and IDO ϩ cell density rose by (62%, P Ͻ 0.05). CD39 expression dropped by 30% (P Ͻ 0.05) in microglia and blood vessels. With 10 wk of systemic treatment using minocycline, an anti-inflammatory agent that crosses the blood-brain barrier, MMP-2, IDO, and CD39 levels normalized (P Ͻ 0.05). Our results suggest that increased IDO and early loss of CD39 ϩ protective cells lead to activation of inflammation in sympathetic centers of the CNS. As a downstream effect, the loss of the neuronal survival factors IGFBP-3 and IGF-I and the neurotoxic products of the kynurenine pathway contribute to the loss of neuronal density observed in the HYPO in T1D.

show abstract

Section: E694mentioning

confidence: 99%

Section: /Cd39mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice

Thinschmidt

Caballero

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…The mechanism for such selectivity in CRF expression within a particular subgroup of magnocellular neurons in diabetic rats is not clear. Uncontrolled diabetes apparently triggers the synthesis of both OT and AVP (Luo et al 2002). The selectivity for CRF expression in OT-ir but not AVP-ir neurons has been reported in osmotic stress (Dohanics et al 1990, Imaki et al 2001a, whereas insulin-induced hypoglycemia promotes CRF and AVP colocalization (Paulmyer-Lacroix et al 1994).…”

Section: Discussionmentioning

confidence: 90%

Corticotropin-releasing factor and its receptors in the brain of rats with insulin and corticosterone deficits

Huang¹,

Timofeeva²,

Richard³

2006

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The expression of genes encoding corticotropin-releasing factor (CRF) and its receptor type-1 (CRF 1 R) and type-2a (CRF 2 R) has been studied in the brain of rats with streptozotocin (STZ)-induced diabetes and adrenalectomy (ADX). Diabetic rats had a lower body weight compared to control rats. Food and water intake were increased in diabetic rats and decreased in ADX animals. The plasma corticosterone levels measured at the nadir of the circadian rhythm were significantly higher in diabetic rats compared to non-diabetic animals. STZ-diabetic rats demonstrated an induction of expression of CRF mRNA in the magnocellular part of the paraventricular hypothalamic nucleus (PVN) and in the supraoptic nucleus (SON), whereas the CRF transcript in the parvocellular PVN was significantly lower in rats with insulin deficiency. ADX strongly triggered the expression of CRF mRNA in the parvocellular neurons of the PVN in both nondiabetic and diabetic rats, and it decreased magnocellular CRF mRNA in diabetic animals. The expression of the CRF 1 R in the parvocellular and magnocellular PVN and in the SON was induced by diabetes and decreased after ADX. The levels of the CRF 2 R mRNA in the ventromedial hypothalamic nucleus (VMH) were significantly lower in diabetic rats without any noticeable effects of ADX. The present results suggest opposite effects of insulin and corticosterone deficiency on the hypophysiotropic CRF and the CRF 1 R mRNA contents, whereas the expression of CRF 2 R was mostly related to insulin, but not to the corticosterone status.

show abstract

“…Pituicytes are thought to play an important role in the modulation of neurohormone release under different conditions by undergoing morphological changes [for review, see 24]and/or internalizing neurosecretions [25]. In addition to hypoinsulinemia, STZ treatment causes marked hyperglycemia, plasma hyperosmolality and polydipsia [21, 26], with pronounced increases in arginine vasopressin (AVP) and oxytocin (OT) in hypothalamic magnocellular neurons and their axons/terminals in the NL [25, 27]. Therefore, to examine the possibly opposing actions of osmotic and leptin-related stimuli on GALP expression, GALP mRNA levels in the NL of STZ-DM and control rats was also examined (a preliminary account of these studies was presented to the Australian Society of Neuroscience in Adelaide, Australia, January 2003).…”

Section: Introductionmentioning

confidence: 99%

Galanin-Like Peptide mRNA Alterations in Arcuate Nucleus and Neural Lobe of Streptozotocin-Diabetic and<i> Obese </i>Zucker Rats

Shen

Gundlach

2004

Neuroendocrinology

View full text Add to dashboard Cite

Galanin-like peptide (GALP) is a 60-amino-acid peptide with structural similarities to galanin and a high affinity for galanin receptors. GALP is expressed by a discrete population of neurons in the arcuate nucleus (ARC) and median eminence of the hypothalamus of several species, including the rat. GALP neurons express leptin receptors and GALP mRNA levels are decreased slightly in fasted rats and stimulated significantly by acute leptin treatment in combination with fasting. In studies to further explore the leptin dependence of GALP expression, we examined GALP mRNA levels in the hypothalamus of obese Zucker and streptozotocin-induced diabetic (STZ-DM) rats. In leptin receptor-deficient obese Zucker rats, with 75% higher body weight than lean littermates, GALP mRNA levels in the ARC were decreased by 75%, while neuropeptide Y (NPY) mRNA levels were increased 7-fold (n = 5, p < 0.001), consistent with earlier reports. In hypoleptinemic diabetic rats with 4.5-fold higher blood glucose and 15% lower body weight than controls, GALP mRNA levels in the ARC were decreased by 90%, while NPY mRNA levels were increased 9-fold (n = 5, p < 0.001). GALP is also expressed by pituicytes in the neural lobe of the rat pituitary gland and GALP expression is increased by osmotic stimulation such as dehydration and salt loading. Thus, in STZ-DM rats that are in a hyperosmotic state with elevated plasma vasopressin levels, GALP mRNA levels were increased by ∼20-fold in the neural lobe relative to control (n = 4, p < 0.001). The current findings are consistent with a strong tonic influence of leptin receptor signalling on hypothalamic GALP expression under normal conditions, and possible abnormalities in GALP neuronal signalling and their putative targets, thyrotropin-releasing hormone and gonadotropin hormone-releasing hormone neurons, under pathophysiological conditions such as diabetes and obesity. Our data in STZ-DM rats also clearly demonstrate that GALP gene expression is differentially regulated in neurons and pituicytes.

show abstract

Neuronal and glial response in the rat hypothalamus–neurohypophysis complex with streptozotocin-induced diabetes

Cited by 50 publications

References 37 publications

Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice

Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice

Corticotropin-releasing factor and its receptors in the brain of rats with insulin and corticosterone deficits

Galanin-Like Peptide mRNA Alterations in Arcuate Nucleus and Neural Lobe of Streptozotocin-Diabetic and<i> Obese </i>Zucker Rats

Contact Info

Product

Resources

About