PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat

2001 ◽  
Vol 281 (5) ◽  
pp. R1426-R1436 ◽  
Author(s):  
Scott B. Evans ◽  
Charles W. Wilkinson ◽  
Kathy Bentson ◽  
Pam Gronbeck ◽  
Aryana Zavosh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autonomic Failure ◽  
Brain Activation ◽  
Brain Regions ◽  
Neuroendocrine Response ◽  
Medial Hypothalamus ◽  
Neuroendocrine Responses ◽  
Hypothalamic Activation

The mechanism(s) underlying hypoglycemia-associated autonomic failure (HAAF) are unknown. To test the hypothesis that the activation of brain regions involved in the counterregulatory response to hypoglycemia is blunted with HAAF, rats were studied in a 2-day protocol. Neuroendocrine responses and brain activation (c-Fos immunoreactivity) were measured during day 2 insulin-induced hypoglycemia (0.5 U insulin · 100 g body wt−1· h−1iv for 2 h) after day 1 hypoglycemia (Hypo-Hypo) or vehicle. Hypo-Hypo animals demonstrated HAAF with blunted epinephrine, glucagon, and corticosterone (Cort) responses and decreased activation of the medial hypothalamus [the paraventricular (PVN), dorsomedial (DMH), and arcuate (Arc) nuclei]. To evaluate whether increases in day 1 Cort were responsible for the decreased hypothalamic activation, Cort was infused intracerebroventricularly (72 μg) on day 1 and the response to day 2 hypoglycemia was measured. Intracerebroventricular Cort infusion failed to alter the neuroendocrine response to day 2 hypoglycemia, despite elevating both central nervous system and peripheral Cort levels. However, day 1 Cort blunted responses in two of the same hypothalamic regions as Hypo-Hypo (the DMH and Arc) but not in the PVN. These results suggest that decreased activation of the PVN may be important in the development of HAAF and that antecedent exposure to elevated levels of Cort is not always sufficient to produce HAAF.

Low concentrations of hydrogen sulphide alter monoamine levels in the developing rat central nervous system

1992 ◽  
Vol 70 (11) ◽  
pp. 1515-1518 ◽  
Author(s):  
B. Skrajny ◽  
R. S. Hannah ◽  
S. H. Roth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Frontal Cortex ◽  
Hydrogen Sulphide ◽  
Chronic Exposure ◽  
Brain Regions ◽  
Target Organs ◽  
Low Concentrations ◽  
The Central Nervous System ◽  
Developing Rat

The central nervous system is one of the primary target organs for hydrogen sulphide (H2S) toxicity; however, there are limited data on the neurotoxic effects of low-dose chronic exposure on the developing nervous system. Levels of serotonin and norepinephrine in the developing rat cerebellum and frontal cortex were determined following chronic exposure to 20 and 75 ppm H2S during perinatal development. Both monoamines were altered in rats exposed to 75 ppm H2S compared with controls; serotonin levels were significantly increased at days 14 and 21 postnatal in both brain regions, and norepinephrine levels were significantly increased at days 7, 14, and 21 postnatal in cerebellum and at day 21 in the frontal cortex. Exposure to 20 ppm H2S significantly increased the levels of serotonin in the frontal cortex at day 21, whereas levels of norepinephrine were significantly reduced in the frontal cortex at days 14 and 21, and at day 14 in the cerebellum.Key words: hydrogen sulphide, monoamines, serotonin, norepinephrine, neurotoxicity.

scholarly journals Neuropathological Findings in a Case of IFIH1-Related Aicardi–Goutières Syndrome

2019 ◽  
Vol 22 (6) ◽  
pp. 566-570
Author(s):  
Ahmed Gilani ◽  
Laura A Adang ◽  
Adeline Vanderver ◽  
Abigail Collins ◽  
BK Kleinschmidt-DeMasters
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Atrophy ◽  
Cardiopulmonary Arrest ◽  
Brain Regions ◽  
Variable Degree ◽  
Expression Data ◽  
Ultrastructural Examination ◽  
The Central Nervous System ◽  
Gross Examination

Aicardi–Goutières syndrome (AGS) is a rare syndrome characterized by calcification, diffuse demyelination, and variable degree of brain atrophy. The syndrome is genetically heterogeneous with mutations in 7 genes, including TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1 (interferon-induced helicase c domain-containing protein 1) associated with the syndrome, so far. These mutations lead to the overproduction of α-interferon within the central nervous system. Mutations in IFIH1 have been recently described in a subset of AGS, with only 1 previous report of neuropathological findings. We report neuropathological findings in a second case of AGS with a known mutation in IFIH1 gene. The patient is a 16-year-old adolescent boy with early-onset symptoms that progressed to profound loss of cognitive and motor functions. The patient experienced sudden cardiopulmonary arrest at the age of 16 years. At autopsy, the cause of death was determined to be pulmonary thromboembolism. Neuropathological examination revealed microcephaly (brain weight: 916 g) with relatively mild brain atrophy on gross examination. Microscopic examination revealed multifocal calcifications limited to small to medium central nervous system arteries (no evidence of calcification in other organs), involving bilateral cerebral cortex, basal ganglia, thalamus, and cerebellum. Ultrastructural examination showed Calcospherules limited to the vessel walls and the perivasulcar area without evidence of neuronal ferrugination or tubuloreticular bodies. The extent of calcifications was variable across different brain regions, resembling findings in previously reported cases and correlated with the extent of IFIH1 protein expression (data derived from Allen Brain Institute). AGS is a rare cause of brain calcifications that can closely mimic congenital and neonatal infections such as Rubella and similar infections.

scholarly journals Inhibition of Brain Prostaglandin Endoperoxide Synthase-2 Prevents the Preparturient Increase in Fetal Adrenocorticotropin Secretion in the Sheep Fetus

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4128-4136 ◽  
Author(s):  
Jason Gersting ◽  
Christine E. Schaub ◽  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Fetal Brain ◽  
Brain Regions ◽  
Acth Secretion ◽  
Fetal Sheep ◽  
Prostaglandin Endoperoxide ◽  
Fetal Plasma ◽  
Prostaglandin Endoperoxide Synthase

Maturation of the fetal hypothalamus-pituitary-adrenal axis is critical for the timely somatic development of the fetus and readiness for birth. Recently, we proposed that prostaglandin generation within the fetal central nervous system is critical for the modulation of hypotension-induced fetal ACTH secretion. The present study was designed to test the hypothesis that the preparturient increase in fetal ACTH secretion is dependent upon fetal central nervous system prostaglandin synthesis mediated by the activity of prostaglandin endoperoxide synthase (PGHS)-2 (cyclooxygenase-2) in the fetal brain. We performed two studies in chronically catheterized fetal sheep. In the first study, we infused nimesulide or vehicle intracerebroventricularly (icv) into singleton fetal sheep and collected blood samples until spontaneous parturition. Nimesulide significantly delayed parturition, and inhibited fetal ACTH and proopiomelanocortin secretion but did not prevent the preparturient increase in fetal plasma cortisol concentration. In the second study, we used twin fetuses. One fetus received intracerebroventricular nimesulide and the other intracerebroventricular vehicle. Nimesulide reduced brain tissue concentrations of prostaglandin estradiol, while not affecting plasma prostaglandin E2 concentrations, demonstrating an action restricted to the fetal brain. Nimesulide reduced PGHS-2 mRNA and increased PGHS-2 protein, while not altering PGHS-1 mRNA or protein in most brain regions, suggesting an effect of the inhibitor on PGHS-2 turnover and relative specificity for PGHS-2 in vivo. We conclude that the preparturient increase in fetal ACTH and proopiomelanocortin is dependent upon the activity of PGHS-2 in the fetal brain. However, we also conclude that the timing of parturition is not solely dependent upon ACTH in this species.

scholarly journals Hindbrain lactostasis regulates hypothalamic AMPK activity and metabolic neurotransmitter mRNA and protein responses to hypoglycemia

2014 ◽  
Vol 306 (7) ◽  
pp. R457-R469 ◽  
Author(s):  
Amit D. Gujar ◽  
Baher A. Ibrahim ◽  
Pratistha Tamrakar ◽  
Ajeesh Koshy Cherian ◽  
Karen P. Briski
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Fourth Ventricle ◽  
Brain Regions ◽  
Monocarboxylate Transporter ◽  
Catecholaminergic Neurons ◽  
Lateral Hypothalamic ◽  
Metabolic Monitoring ◽  
Ampk Activity ◽  
6 Hydroxydopamine

Nerve cell metabolic activity is monitored in multiple brain regions, including the hypothalamus and hindbrain dorsal vagal complex (DVC), but it is unclear if individual metabolosensory loci operate autonomously or interact to coordinate central nervous system (CNS) reactivity to energy imbalance. This research addressed the hypothesis that hypoglycemia-associated DVC lactoprivation stimulates hypothalamic AMPK activity and metabolic neurotransmitter expression. As DVC catecholaminergic neurons express biomarkers for metabolic monitoring, we investigated whether these cells are a source of lactate deficit signaling to the hypothalamus. Caudal fourth ventricle (CV4) infusion of the glucose metabolite l-lactate during insulin-induced hypoglycemia reversed changes in DVC A2 noradrenergic, arcuate neuropeptide Y (NPY) and pro-opiomelanocortin (POMC), and lateral hypothalamic orexin-A (ORX) neuronal AMPK activity, coincident with exacerbation of hypoglycemia. Hindbrain lactate repletion also blunted hypoglycemic upregulation of arcuate NPY mRNA and protein. This treatment did not alter hypoglycemic paraventricular oxytocin (OT) and lateral hypothalamic ORX mRNA profiles, but exacerbated or reversed adjustments in OT and ORX neuropeptide synthesis, respectively. CV4 delivery of the monocarboxylate transporter inhibitor, 4-CIN, increased A2 phosphoAMPK (pAMPK), elevated circulating glucose, and stimulated feeding, responses that were attenuated by 6-hydroxydopamine pretreatment. 4-CIN-infused rats exhibited increased (NPY, ORX neurons) or decreased (POMC neurons) pAMPK concurrent with hyperglycemia. These data show that hindbrain lactoprivic signaling regulates hypothalamic AMPK and key effector neurotransmitter responses to hypoglycemia. Evidence that A2 AMPK activity is lactate-dependent, and that DVC catecholamine cells are critical for lactoprivic control of glucose, feeding, and hypothalamic AMPK, implies A2 derivation of this metabolic regulatory stimulus.

Congenital Disorders of Autophagy: What a Pediatric Neurologist Should Know

2017 ◽  
Vol 49 (01) ◽  
pp. 018-025 ◽  
Author(s):  
Darius Ebrahimi-Fakhari
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autosomal Recessive ◽  
Neurological Diseases ◽  
Single Gene ◽  
Central Nervous System Involvement ◽  
Brain Regions ◽  
Nervous System Development ◽  
Congenital Disorders ◽  
Childhood Onset

AbstractAutophagy is a fundamental and conserved intracellular pathway that mediates the degradation of macromolecules and organelles in lysosomes. Proper autophagy function is important for central nervous system development and neuronal function. Over the last 5 years, several single gene disorders of the autophagy pathway have emerged: EPG5-associated Vici syndrome, WDR45-associated β-propeller protein-associated neurodegeneration, SNX14-associated autosomal-recessive spinocerebellar ataxia 20, ATG5-associated autosomal-recessive ataxia syndrome, SQSTM1/p62-associated childhood-onset neurodegeneration, and several forms of the hereditary spastic paraplegias. This novel and evolving group of disorders is characterized by prominent central nervous system involvement leading to brain malformations, developmental delay, intellectual disability, epilepsy, movement disorders, and neurodegeneration. Predominant involvement of the long white matter tracts and the cerebellum are anatomic and imaging hallmarks, with common findings that include a thinning of the corpus callosum and cerebellar hypoplasia or atrophy. A storage disease phenotype by clinical or imaging criteria is present in some diseases. Most congenital disorders of autophagy are progressive and over time involve pathology in multiple brain regions. This review provides a detailed clinical, imaging and genetic characterization of congenital disorders of autophagy and highlights the importance of this pathway for childhood-onset neurological diseases.

Drp1 widely, yet heterogeneously distributes in mice central nervous system

2020 ◽  
Author(s):  
Ting-Ting Luo ◽  
Chun-Qiu Dai ◽  
Jia-Qi Wang ◽  
Zheng-Mei Wang ◽  
Yi Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Malignant Glioma ◽  
Expression Patterns ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Heterogeneous Distribution ◽  
Human Malignant Glioma ◽  
The Impact ◽  
The Relationship

Abstract Objectives: Drp1 is wildly expressed and plays a role in inducing mitochondrial fission process. It is confirmed that many diseases are associated with Drp1 and mitochondria. However, since the exact Drp1 is not specifically distributed, it is hard to determine the impact of anti-Drp1 molecules on human body and where the Drp1 inhibitor functions. Methods: We visualized distribution of Drp1 in different brain regions, and explicated the relationship between Drp1 and mitochondria. GAD67-GFP knock-in mice were utilized to detect the expression patterns of Drp1 on the GABAergic neurons. And we further analyzed Drp1 expression in human malignant glioma tissue. Results: Drp1 widely but heterogeneously distributed in central nervous system. Further observation indicated that Drp1 was highly and heterogeneously expressed in inhibitory neurons. Under transmission electron microscope, Drp1 distribution in dendrites was higher than other areas in neurons and only a small amount of Drp1 was located on mitochondria. In human malignant glioma, Drp1 fluorescence intensity increased from grade I-III, while grade IV showed the descending trend. Conclusion: In this study, we observed Drp1 widely yet heterogeneously distributed in central nervous system. Drp1 heterogeneous distribution may be related with the occurrence and development of neurologic disease. We hope that the relationship between Drp1 and mitochondria may give the therapeutic guidance.

scholarly journals Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins

2003 ◽  
Vol 161 (4) ◽  
pp. 805-816 ◽  
Author(s):  
Susumu Tomita ◽  
Lu Chen ◽  
Yoshimi Kawasaki ◽  
Ronald S. Petralia ◽  
Robert J. Wenthold ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Cerebellar Granule Cells ◽  
Surface Expression ◽  
Brain Regions ◽  
Regulatory Proteins ◽  
General Role ◽  
Receptor Complexes

Functional expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in cerebellar granule cells requires stargazin, a member of a large family of four-pass transmembrane proteins. Here, we define a family of transmembrane AMPA receptor regulatory proteins (TARPs), which comprise stargazin, γ-3, γ-4, and γ-8, but not related proteins, that mediate surface expression of AMPA receptors. TARPs exhibit discrete and complementary patterns of expression in both neurons and glia in the developing and mature central nervous system. In brain regions that express multiple isoforms, such as cerebral cortex, TARP–AMPA receptor complexes are strictly segregated, suggesting distinct roles for TARP isoforms. TARPs interact with AMPA receptors at the postsynaptic density, and surface expression of mature AMPA receptors requires a TARP. These studies indicate a general role for TARPs in controlling synaptic AMPA receptors throughout the central nervous system.

scholarly journals Effects of ACTH, dexamethasone, and adrenalectomy on 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system

2007 ◽  
Vol 196 (2) ◽  
pp. 305-311 ◽  
Author(s):  
Ping Ye ◽  
Christopher J Kenyon ◽  
Scott M MacKenzie ◽  
Katherine Nichol ◽  
Jonathan R Seckl ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adrenal Gland ◽  
Brain Regions ◽  
Dietary Sodium ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Aldosterone Synthase ◽  
The Central Nervous System ◽  
Wistar Kyoto

Using a highly sensitive quantitative RT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs, we previously demonstrated that CYP11B2 expression in the central nervous system (CNS) is subject to regulation by dietary sodium. We have now quantified the expression of these genes in the CNS of male Wistar Kyoto (WKY) rats in response to systemic ACTH infusion, dexamethasone infusion, and to adrenalectomy. CYP11B1 and CYP11B2 mRNA levels were measured in total RNA isolated from the adrenal gland and discrete brain regions using real-time quantitative RT-PCR. ACTH infusion (40 ng/day for 7 days, N=8) significantly increased CYP11B1 mRNA in the adrenal gland, hypothalamus, and cerebral cortex compared with animals infused with vehicle only. ACTH infusion decreased adrenal CYP11B2 expression but increased expression in all of the CNS regions except the cortex. Dexamethasone (10 μg/day for 7 days, N=8) reduced adrenal CYP11B1 mRNA compared with control animals but had no significant effect on either gene's expression in the CNS. Adrenalectomy (N=6 per group) significantly increased CYP11B1 expression in the hippocampus and hypothalamus and raised CYP11B2 expression in the cerebellum relative to sham-operated animals. This study confirms the transcription of CYP11B1 and CYP11B2 throughout the CNS and demonstrates that gene transcription is subject to differential regulation by ACTH and circulating corticosteroid levels.

scholarly journals Disorders of Neuronal Migration

1987 ◽  
Vol 14 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Peter G. Barth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Migration ◽  
Brain Regions ◽  
Distinct Pattern ◽  
Basic Knowledge ◽  
Detailed Knowledge ◽  
Important Process ◽  
The Central Nervous System ◽  
Environmental Causes

Abstract:Neuronal migration constitutes one of the major processes by which the central nervous system takes shape. Detailed knowledge about this important process now exists for different brain regions in rodent and monkey models as well as in the human. In the human, distinct genetic, chromosomal and environmental causes are known that affect neuronal migration, often in a morphologically distinct pattern, but the underlying pathological mechanisms are largely unknown. This review is intended to integrate our basic knowledge of the field with the accumulated intelligence on a large number of disorders and syndromes that represent the human part of the story.

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