Regulation of α2A-adrenoceptor expression by chronic stress in neurons of the brain stem

Meyer, Heiko; Palchaudhuri, Monika; Scheinin, Mika; Flügge, Gabriele

doi:10.1016/s0006-8993(00)02787-6

Cited by 54 publications

(47 citation statements)

References 36 publications

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“…In situ hybridization experiments were performed as described (14). Briefly, frozen brains from adult male Wistar rats (2 months old; from Harlan Winkelmann, Borchen, Germany) were cut on a cryostat.…”

Section: Methodsmentioning

confidence: 99%

The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation

Alfonso

Fernández

Cooper

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

105

173

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Neuronal remodeling is a fundamental process by which the brain responds to environmental influences, e.g., during stress. In the hippocampus, chronic stress causes retraction of dendrites in CA3 pyramidal neurons. We have recently identified the glycoprotein M6a as a stress-responsive gene in the hippocampal formation. This gene is down-regulated in the hippocampus of both socially and physically stressed animals, and this effect can be reversed by antidepressant treatment. In the present work, we analyzed the biological function of the M6a protein. Immunohistochemistry showed that the M6a protein is abundant in all hippocampal subregions, and subcellular analysis in primary hippocampal neurons revealed its presence in membrane protrusions (filopodia͞ spines). Transfection experiments revealed that M6a overexpression induces neurite formation and increases filopodia density in hippocampal neurons. M6a knockdown with small interference RNA methodology showed that M6a low-expressing neurons display decreased filopodia number and a lower density of synaptophysin clusters. Taken together, our findings indicate that M6a plays an important role in neurite͞filopodium outgrowth and synapse formation. Therefore, reduced M6a expression might be responsible for the morphological alterations found in the hippocampus of chronically stressed animals. Potential mechanisms that might explain the biological effects of M6a are discussed. chronic stress ͉ hippocampus T he adult nervous system can be strongly influenced by sensory input from the outside environment. For example, prolonged exposure to adverse situations can have severe consequences for the brain, conferring susceptibility to certain psychiatric disorders. Indeed, chronic stress is one of the main factors known to trigger depression in humans (1). One of the most extensively studied regions in the brain is the hippocampal formation, which possesses a remarkable degree of plasticity and is particularly sensitive to stress. Studies in rodents and tree shrews demonstrated that chronic stress can cause alterations in neuronal processes. Stressed animals show morphological changes in CA3 pyramidal neurons, characterized by a reduction of apical dendritic branching and total dendritic length (2, 3). In addition, stressed rats also display a marked retraction of thorny excrescences and reduced synaptic density (4-6). Interestingly, antidepressant treatment can block these stress effects (7). Although there has been important progress regarding the understanding of the stress response and antidepressant action, the molecular pathways underlying these plastic alterations still remain largely unknown.By using subtractive hybridization libraries, we have recently identified the gene encoding the glycoprotein M6a as a stressresponsive gene. Expression levels for M6a are decreased in hippocampal tissue of tree shrews subjected to chronic psychosocial stress, and this down-regulation is prevented by chronic administration of the antidepressant clomipramine (8). Moreover, mice exp...

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Section: Methodsmentioning

confidence: 99%

The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation

Alfonso

Fernández

Cooper

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

105

173

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“…Alpha 2A -AR knockout mice cannot reduce NA overflow in the prefrontal cortex after a stressful stimulus (Ihalainen and Tanila 2002). There are also postsynaptic alpha 2 -ARs on non-noradrenergic neurons, for example, subtype A is expressed in glutamatergic neurons of the medulla oblongata (Meyer et al 2000). Subtype C in the striatum is expressed by GABAergic neurons (Holmberg et al 1999).…”

Section: Alpha 2 -Adrenoceptorsmentioning

confidence: 99%

“…1). Analysis of receptor subtype specific RNA in single noradrenergic LC neurons revealed that it is the subtype A autoreceptor whose expression is reduced by the chronic stress (Meyer et al 2000). Diminished autoreceptor expression causes impaired feedback inhibition of NA release and, concomitantly, higher levels of the neurotransmitter in projection regions of the LC (see .…”

Section: Alpha 2 -Adrenoceptorsmentioning

confidence: 99%

Perturbations in brain monoamine systems during stress

2003

Self Cite

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Monoamines modulate the activity of many neurons and there is evidence that a balanced synthesis of central nervous monoamines is a prerequisite for normal brain functioning. Stress accelerates both release and turnover of brain monoamines and the resulting fluctuations in concentrations affect various parameters within neurotransmitter systems. Acute stress leads to only transient alterations in monoamine systems so that homeostasis can be restored, in contrast, chronic stress accompanied by repetitive and/or prolonged stimulation of monoaminergic neurons can induce a long-lasting imbalance in central nervous neurotransmitter systems. Accordingly, stress-induced changes in brain monoamine systems are suspected to contribute to psychiatric diseases such as depression. The present paper gives a short overview of stress effects on brain monoamines and their receptors.

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“…These pathways are activated by stress (Pacak et al 1995) and mediate the release of CRH and adrenocorticotropin through the ␣ 1 -adrenoceptors (Plotsky et al 1989;Szafarczyk et al 1987). On the other hand, adrenalectomy (ADX) or removal of circulating corticosterone in the rat increases the stress-induced release of noradrenaline (Pacak et al 1995) and both ␣ 2A - (Feuvrier et al 1999) and ␣ 1B -adrenoceptor mRNA levels in the PVN (Day et al 1999), whereas chronic stress reduces the ␣ 2A -adrenoceptor mRNA levels in selective brain regions (Meyer et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Adrenalectomy Potentiates Noradrenergic Suppression of GABAergic Transmission in Parvocellular Neurosecretory Neurons of Hypothalamic Paraventricular Nucleus

Yang

Li²,

Shin³

et al. 2008

Journal of Neurophysiology

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Adrenalectomy potentiates noradrenergic suppression of GABAergic transmission in parvocellular neurosecretory neurons of hypothalamic paraventricular nucleus. J Neurophysiol 99: 514 -523, 2008. First published November 21, 2007 doi:10.1152/jn.00568.2007. Glucocorticoids are known to regulate both the noradrenergic and GABAergic inputs to the paraventricular nucleus (PVN). However, little is known about the effects of glucocorticoids on the interaction of these two input systems. Here we examined the effects of bilateral adrenalectomy (ADX) on the noradrenergic modulation of GABAergic transmission in the type II PVN neurons labeled with a retrograde dye injected into the pituitary stalk. Noradrenaline either reduced or augmented the frequency of spontaneous inhibitory postsynaptic current (sIPSC) without changing the amplitude and decay time constant. These effects were blocked by ␣ 2A -and ␣ 1A/1L -adrenoceptor antagonists, respectively. ADX increased the proportion of the neurons showing the noradrenergic reduction and the extent of reduction in the IPSC frequency. The ADX-induced changes were reversed by supplementation of ADX rats with corticosterone (10-mg pellet). ADX also potentiated the noradrenergic reduction in the frequency of miniature IPSC and paired-pulse facilitation of evoked IPSC. BRL 44408 (3 M), a ␣ 2A -adrenoceptor antagonist, blocked the noradrenergic reduction in ADX rats. Corticotropin-releasing hormone and/or vasopressin transcripts were detected in neurons displaying noradrenergic augmentation or reduction of IPSC frequency. ADX enhanced the proportion of neurons expressing corticotropin-releasing hormone. Collectively, the results suggest that depletion of corticosterone by ADX markedly potentiates the noradrenergic suppression of GABAergic transmission mediated by the ␣ 2A -adrenoceptors on the GABAergic terminals in the parvocellular neurosecretory PVN neurons. These results may provide a novel synaptic mechanism for the glucocorticoid-induced plasticity in the noradrenergic modulation of neuroendocrine function of the PVN.

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Regulation of α2A-adrenoceptor expression by chronic stress in neurons of the brain stem

Cited by 54 publications

References 36 publications

The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation

The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation

Perturbations in brain monoamine systems during stress

Adrenalectomy Potentiates Noradrenergic Suppression of GABAergic Transmission in Parvocellular Neurosecretory Neurons of Hypothalamic Paraventricular Nucleus

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