Biomedical subjects

Carola Eva

Publications and source records attributed to Carola Eva.

7 recordsLinked to original sources

PubMed2006

Physiology and gene regulation of the brain NPY Y1 receptor.

Neuropeptide Y (NPY) is one of the most prominent and abundant neuropeptides in the mammalian brain where it interacts with a family of G-protein coupled receptors, including the Y(1) receptor subtype (Y(1)R). NPY-Y(1)R signalling plays a prominent role in the regulation of several behavioural and physiological functions including feeding behaviour and energy balance, sexual hormone secretion, stress response, emotional behaviour, neuronal excitability and ethanol drinking. Y(1)R expression is regulated by neuronal activity and peripheral hormones. The Y(1)R gene has been isolated from rodents and humans and it contains multiple regulatory elements that may participate in the regulation of its expression. Y(1)R expression in the hypothalamus is modulated by changes in energetic balance induced by a wide variety of conditions (fasting, pregnancy, hyperglycaemic challenge, hypophagia, diet induced obesity). Estrogens up-regulate responsiveness to NPY to stimulate preovulatory GnRH and gonadotropin surges by increasing Y(1)R gene expression both in the hypothalamus and the pituitary. Y(1)R expression is modulated by different kinds of brain insults, such as stress and seizure activity, and alteration in its expression may contribute to antidepressant action. Chronic modulation of GABA(A) receptor function by benzodiazepines or neuroactive steroids also affects Y(1)R expression in the amygdala, suggesting that a functional interaction between the GABA(A) receptor and Y(1)R mediated signalling may contribute to the regulation of emotional behaviour. In this paper, we review the state of the art concerning Y(1)R function and gene expression, including our personal contribution to many of the subjects mentioned above.

Alcohol Drinking↗

PubMed2006

Role of brain neuroactive steroids in the functional interplay between the GABA(A) and the NPY-Y1 receptor mediated signals in the amygdala.

Various lines of evidence suggest a functional interaction between GABA(A) and Neuropeptide Y (NPY)-Y(1) receptor (Y(1)R) mediated transmissions in various brain regions, which can be important in the regulation of sedation, feeding, anxious behaviour and neuronal excitability. By using a transgenic mouse model carrying the murine Y(1)R gene promoter fused to the lacZ reporter gene (Y(1)R/LacZ mice), we showed that prolonged pharmacologically or physiologically induced changes in the cerebrocortical concentrations of the neuroactive steroids 3alpha-hydroxy-5alpha-pregnan- 20-one (3alpha,5alpha TH PROG) and tetrahydrodeoxycorticosterone (3alpha,5alpha TH DOC) increases Y(1)R/LacZ transgene expression in the central and medial amygdala, an effect similar to that induced by long-term treatment with positive modulators of the GABA(A) receptor complex (diazepam or abecarnil). We also demonstrated that fluctuations in the cerebrocortical concentrations of 3alpha,5alpha-TH PROG and 3alpha,5alpha TH DOC during voluntary ethanol consumption and ethanol withdrawal induces a marked increase in Y(1)R gene expression that becomes apparent 48 h after withdrawal. These data provide evidence that neuroactive steroids may play an important role in the functional interaction between the GABA(A) receptor and NPY-Y(1)R mediated pathways in the amygdala, which might represent an important regulatory mechanism for modulation of several functions, including ethanol withdrawal.

Amygdala↗

PubMed2004

Increased expression of the gene for the Y1 receptor of neuropeptide Y in the amygdala and paraventricular nucleus of Y1R/LacZ transgenic mice in response to restraint stress.

A sustained increase in the brain concentrations of neuroactive steroids was previously shown to induce Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice which harbour a construct comprising the murine Y1 receptor gene promoter and the lacZ reporter gene. We now investigated the effects of restraint stress on both the cerebrocortical concentrations of neuroactive steroids and Y1 receptor gene expression in the amygdala and hypothalamic paraventricular nucleus (PVN) of Y1R/LacZ transgenic mice. The cerebrocortical concentrations of allopregnanolone and allotetrahydrodeoxycorticosterone were significantly increased immediately after a 1-h exposure to restraint stress and had returned to control values within 30 min. Expression of Y1R/LacZ was increased in the amygdala and PVN 6 h after restraint. The 5alpha-reductase inhibitor finasteride, that prevented the increase in neuroactive steroid concentrations, did not block that in transgene expression induced by 1-h restraint. Daily exposure to restraint for 10 days also increased the cerebrocortical concentrations of neuroactive steroids but failed to affect transgene expression. Acute but not repeated restraint thus increases Y1 receptor gene expression in the amygdala and PVN, suggesting that tolerance develops towards this stressor. The effect of acute restraint is not mediated by the increase in the brain concentrations of neuroactive steroids but may rather reflect a ligand-induced increase in Y1 receptor gene transcription. Data support a role of Y1 receptors in the behavioural and neuroendocrine responses to stress.

Amygdala↗

PubMed2004

Neuroanatomical and pharmacological evidence for a functional interaction between GABAergic and NPY-Y1 transmission in the amygdala of Y1R/LacZ transgenic mice.

Several lines of evidence indicate that GABA and neuropeptide Y (NPY) are functionally coupled and may interact in the regulation of fear- and anxiety-induced behavior. Neuroanatomical studies demonstrated that GABA and NPY coexist in neurons of the amygdaloid complex and that NPY may directly modulate the activity of GABAergic neurons by stimulating Y1 receptors. By using a transgenic mouse model harboring a construct comprising the murine Y1 receptor gene promoter fused to a lacZ reporter gene (Y1R/LacZ mice), we showed that long-term treatment with positive (diazepam or abecarnil) or negative (FG7142) modulators of GABAA receptor function induced a marked increase or decrease, respectively, in Y1 receptor gene expression in the amygdala. Furthermore, we demonstrated that a sustained increase in the brain concentrations of neuroactive steroids, induced by pharmacological treatment or by physiological conditions such as pregnancy, increases Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice, an effect similar to that induced by diazepam or abecarnil. These data provide evidence of a functional interaction between GABAergic and NPY-Y1 mediated transmission and suggest that neuroactive steroids may play an important role in the regulation of the NPY transmission. Finally, our data support a role of Y1 receptors in the behavioral and neuroendocrine responses to stress that, however, appears to be independent on the activation of the GABAergic system.

Amygdala↗

PubMed2003

Evidence of altered neuropeptide Y content and neuropeptide Y1 receptor gene expression in the hypothalamus of pregnant transgenic mice.

Alterations in the density of neuropeptide Y (NPY)-immunoreactive fibers and of NPY1 receptor gene expression in the hypothalamus of Y1R/LacZ transgenic pregnant mice were investigated. In the paraventricular nucleus of mice on the 18th d of pregnancy NPY immunoreactivity was significantly decreased, and NPY1 receptor gene expression, as measured by histochemical staining of beta-galactosidase and in situ hybridization of NPY1 receptor mRNA, was significantly increased compared with those in estrous mice. Conversely, pregnant transgenic mice displayed a significant induction of NPY immunoreactivity and a reduction of NPY1 receptor gene expression in the ventromedial nucleus. A significant increase in Y1R/LacZ transgene expression and NPY1 receptor mRNA, but no changes in NPY immunoreactivity were observed in the arcuate nucleus of mice on the 18th d of pregnancy. These results suggest that the elevated expression of NPY in the ventromedial nucleus may contribute to the state of leptin resistance that occurs during pregnancy.

Animals↗

PubMed2002

Decrease of the D4 dopamine receptor messenger RNA expression in lymphocytes from patients with major depression.

OBJECTIVES: The evaluation of the possible role of dopamine in psychiatric disorders has been limited by the relative inadequacy of tools. A tempting approach to examine alterations of dopaminergic system in major depression is to examine the expression of dopamine receptors in peripheral blood mononuclear cells (PBMC). METHODS: D4 dopamine receptor (D4DR) messenger RNA (mRNA) expression in PBMC from 12 patients with major depressive disorder was examined before and after an 8-week treatment with paroxetine at 20-50 mg/day. Ten healthy subjects were analyzed in parallel. The relative content of D4DR mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). using beta-actin as internal standard. RESULTS: D4DR mRNA levels were significantly decreased in untreated depressed patients as compared to controls. D4DR mRNA expression returned to control levels after paroxetine treatment, when patients achieved a significant improvement of depressive symptoms. CONCLUSIONS: Results of our study suggest the role of PBMC D4DR mRNA expression as a peripheral marker of the central dopaminergic function in major depression.

Actins↗

PubMed2002

Changes in expression of the neuropeptide Y Y1 receptor gene in the medial amygdala of transgenic mice during pregnancy and after delivery.

Long-term administration of progesterone or allopregnanolone was previously shown to increase Y1 receptor gene expression in the medial amygdala of Y1R/LacZ transgenic mice, which harbor a construct comprising the murine Y1 receptor gene promoter and a lacZ reporter. We have now investigated the effects of physiological fluctuations in the cerebrocortical concentrations of neuroactive steroids during pregnancy on Y1R/LacZ transgene expression by quantitative histochemical analysis of beta-galactosidase activity. Cerebrocortical concentrations of progesterone and its metabolites allopregnanolone and allotetrahydrodeoxycorticosterone were increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Transgene expression in the medial amygdala was also increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Similar results were obtained after analysis of Y1R mRNA levels in the medial amygdala of pregnant mice by in situ hybridization. Administration of the 5alpha-reductase inhibitor finasteride to pregnant mice prevented both the increase in the cerebrocortical concentrations of neuroactive steroids as well as the increase in transgene expression. These data suggest that fluctuations in the brain concentrations of endogenous neuroactive steroids during pregnancy are associated with changes in Y1 receptor gene expression in the medial amygdala, further supporting a functional interaction between the GABAergic and NPY-Y1 receptor systems.

Amygdala↗