GABAA receptor subunit expression within hypophysiotropic CRH neurons: A dual hybridization histochemical study

Cullinan, William E.

doi:10.1002/(sici)1096-9861(20000410)419:3<344::aid-cne6>3.0.co;2-z

Cited by 115 publications

(68 citation statements)

References 39 publications

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“…Notably, the beta-1 and beta-2 subunits of the GABA-A receptor are down-regulated in the PVNmpd (but not PVNpm) by chronic unpredictable stress (Cullinan, 2000), consistent with reduced efficacy of GABA signaling (and hence, inhibition) specifically in parvocellular PVN neurons. These data are supported by electrophysiological studies documenting reduced GABA signaling in PVN slices from chronically-stressed rats (Verkuyl et al, 2004).…”

Section: Activation Of Pvn Neurons By Acute Stressorsmentioning

confidence: 67%

Chronic stress plasticity in the hypothalamic paraventricular nucleus

Herman

Flak

Jankord

2008

Progress in Brain Research

122

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Proper integration and execution of the physiological stress response is essential for maintaining homeostasis. Stress responses are controlled in large part by the paraventricular nucleus of the hypothalamus, which contains three functionally distinct neural populations that modulate multiple stress effectors: 1) hypophysiotrophic PVN neurons that directly control the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis; 2) magnocellular neurons and their secreted neurohypophysial peptides; and 3) brainstem and spinal cord projecting neurons that regulate autonomic function. Evidence for activation of PVN neurons during acute stress exposure demonstrates extensive involvement of all three effector systems. In addition, all PVN regions appear to participate in chronic stress responses. Within the hypophysiotrophic neurons, chronic stress leads to enhanced expression of secreted products, reduced expression of glucocorticoid receptor and GABA receptor subunits, and enhanced glutamate receptor expression. In addition, there is evidence for chronic stress-induced morphological plasticity in these neurons, with chronic drive causing changes in cell size and altered GABAergic and glutamatergic innervation. The response of the magnocellular system varies with different chronic exposure paradigms, with changes in neurohypophysial peptide gene expression, peptide secretion and morphology seen primarily after intense stress exposure. The preautonomic cell groups are less well studied, but are likely to be associated with chronic stress-induced changes in cardiovascular function. Overall, the PVN is uniquely situated to coordinate responses of multiple stress effector systems in the face of prolonged stimulation, and likely plays a role in both adaptation and pathology associated with chronic stress. Keywordsvasopressin; corticotropin releasing hormone; magnocellular; parvocellular; preautonomic The paraventricular nucleus of the hypothalamus is a critical node for regulation and orchestration of physiological stress responses. Neurons resident in the PVN control three major physiological effector pathways: the hypothalamo-pituitary-adrenocortical (HPA) axis, through neurons in the dorsomedial parvocellular (PVNmpd) and anterior parvocellular (PVNap) divisions of the nucleus; neurohypophysial peptide signals, via magnocellular vasopressin (AVP) and oxytocin (OXT) neurons in the anterior (PVNam), medial (PVNmm) and posterior magnocellular (PVNpm) cell groups; and autonomic regulation, using brainstem and spinal cord projecting neurons in the lateral parvocellular (PVNlp), dorsal parvocellular (PVNdp) and ventromedial parvocellular (PVNmpv) divisions (Swanson and Sawchenko, 1983) (see Fig. 1). The intermingling of three physiologically distinct signaling Address correspondence to: James Herman, PhD, Department of Psychiatry, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript systems places the PVN at the cross-roads f...

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Section: Activation Of Pvn Neurons By Acute Stressorsmentioning

confidence: 67%

Chronic stress plasticity in the hypothalamic paraventricular nucleus

Herman

Flak

Jankord

2008

Progress in Brain Research

122

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“…The CRF and GABA A systems are tightly interconnected, and in the PVN, GABA A receptors colocalize with CRF neurons (Cullinan, 2000). A similar interaction is likely to occur in the cortex.…”

Section: Discussionmentioning

confidence: 91%

A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding

Saavedra

Armando

Bregonzio

et al. 2005

Neuropsychopharmacol

101

100

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Long-term pretreatment with an angiotensin II AT 1 antagonist blocks angiotensin II effects in brain and peripheral organs and abolishes the sympathoadrenal and hypothalamic-pituitary-adrenal responses to isolation stress. We determined whether AT 1 receptors were also important for the stress response of higher regulatory centers. We studied angiotensin II and corticotropin-releasing factor (CRF) receptors and benzodiazepine binding sites in brains of Wistar Hannover rats. Animals were pretreated for 13 days with vehicle or a central and peripheral AT 1 antagonist (candesartan, 0.5 mg/kg/day) via osmotic minipumps followed by 24 h of isolation in metabolic cages, or kept grouped throughout the study (grouped controls). In another study, we determined the influence of a similar treatment with candesartan on performance in an elevated plus-maze. AT 1 receptor blockade prevented the isolation-induced increase in brain AT 1 receptors and decrease in AT 2 binding in the locus coeruleus. AT 1 receptor antagonism also prevented the increase in tyrosine hydroxylase mRNA in the locus coeruleus. Pretreatment with the AT 1 receptor antagonist completely prevented the decrease in cortical CRF 1 receptor and benzodiazepine binding produced by isolation stress. In addition, pretreatment with candesartan increased the time spent in and the number of entries to open arms of the elevated plus-maze, measure of decreased anxiety. Our results implicate a modulation of upstream neurotransmission processes regulating cortical CRF 1 receptors and the GABA A complex as molecular mechanisms responsible for the anti-anxiety effect of centrally acting AT 1 receptor antagonists. We propose that AT 1 receptor antagonists can be considered as compounds with possible therapeutic anti-stress and anti-anxiety properties.

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“…It is equally possible, however, that the CRH and GABA systems are related to each other and together impact the symptom profile of the depressed suicide. In this respect, it was reported that GABAergic agents may influence limbic CRH mRNA expression (Cullinan, 2000;Skelton et al, 2000;Stout et al, 2001;Gilmor et al, 2003), and hence may affect the stressor-provoked CRH response (Cullinan and Wolfe, 2000). Thus, just as CRH may influence monoaminergic (both NE and 5-HT) neuronal functioning, which could potentially influence depression (Ruggiero et al, 1999), CRH-GABA interrelationships may exist that influence affective states.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation in the Suicide Brain: mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABA_AReceptor Subunits in Frontal Cortical Brain Region

Merali¹,

Du²,

Hrdina³

et al. 2004

J. Neurosci.

361

225

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Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH 1 , and CRH 2 receptors, as well as various GABA A receptor subunits (␣1, ␣2, ␣3, ␣4, ␣5, ␦, and ␥2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH 1 , but not CRH 2 , receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the ␣1, ␣3, ␣4, and ␦ receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABA A receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABA A receptor subunit changes, or the disturbed coordination between these GABA A receptor subunits, contribute to depression and/or suicidality or are secondary to the illness/distress associated with it.

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GABAA receptor subunit expression within hypophysiotropic CRH neurons: A dual hybridization histochemical study

Cited by 115 publications

References 39 publications

Chronic stress plasticity in the hypothalamic paraventricular nucleus

Chronic stress plasticity in the hypothalamic paraventricular nucleus

A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding

Dysregulation in the Suicide Brain: mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABA_AReceptor Subunits in Frontal Cortical Brain Region

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GABAA receptor subunit expression within hypophysiotropic CRH neurons: A dual hybridization histochemical study

Cited by 115 publications

References 39 publications

Chronic stress plasticity in the hypothalamic paraventricular nucleus

Chronic stress plasticity in the hypothalamic paraventricular nucleus

A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding

Dysregulation in the Suicide Brain: mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABAAReceptor Subunits in Frontal Cortical Brain Region

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Dysregulation in the Suicide Brain: mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABA_AReceptor Subunits in Frontal Cortical Brain Region