Neuroendocrine and behavioral effects of antisense oligonucleotides

Landgraf, Rainer; Naruo, Tetsuro; Vecsernyés, Miklós; Neumann, Inga D.

doi:10.1530/eje.0.1370326

Cited by 21 publications

(14 citation statements)

References 84 publications

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“…This compensatory upregulation of the protein in response to the ODN knock-down may reflect the interruption of some sort of negative feedback of the SRC-1 protein on the mRNA expression. As a result of antisense administration, untranslated SRC-1 mRNA may have accumulated [antisense oligonucleotides are supposed to increase RNase H activity that would counteract this effect, but this enzyme is apparently not expressed at detectable levels and unlikely to play a major role in the brain (Sawai et al, 1977;Landgraf et al, 1997)], and, with the cessation of the treatment, this accumulated message was translated and resulted in the detected increase in the protein. Feedback loops of this sort between message expression and the protein are common in many vertebrate and invertebrate systems (Han et al, 1999;Allada et al, 2001;Venkatesh et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…We used the third generation antisense ODN, a chimer consisting of locked nucleic acid (LNA) Singh et al, 1998) and deoxyribonucleotides (LNA/DNA/LNA gap-mer) purchased from Proligo (Paris, France). The very high affinity of LNA-containing oligonucleotides for their complementary target RNA, the acceleration of RNase H activity [a fact still disputed in the brain, because RNase H might not be present in this tissue (Sawai et al, 1977;Landgraf et al,, 1997)], and their stability in biological media make these chimers a very convenient tool to regulate gene expression through RNA targeting (Braasch and Corey, 2001;Kurreck et al, 2002). The sequence for the 19-mer antisense spanning the putative start codon of the quail SRC-1 was 5Ј-CAAGgccactcatgtTGAC-3Ј (the LNA monomers are represented by uppercase letters and DNA monomers by lowercase letters), and the scrambled control ODN was 5Ј-CAGAgccactactgt-GTAC-3Ј.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Steroid Receptor Coactivator-1 Blocks Estrogen and Androgen Action on Male Sex Behavior and Associated Brain Plasticity

Charlier¹,

Ball²,

Balthazart³

2005

J. Neurosci.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Inhibition of Steroid Receptor Coactivator-1 Blocks Estrogen and Androgen Action on Male Sex Behavior and Associated Brain Plasticity

Charlier¹,

Ball²,

Balthazart³

2005

J. Neurosci.

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“…Antisense oligonucleotide targeting of specific peptides, including protein products of the IEGs, in discrete anatomic areas has proven to be a fruitful approach in relation to neuroendocrine and behavioral outcome (Chiasson et al, 1992, 1997; Landgraf et al, 1997; Nicot and Pfaff, 1997). A study by Moller et al (1994) investigated the role of amygdaloid induction of c‐ fos in rats that were subjected to the Vogel conflict test.…”

Section: Discussionmentioning

confidence: 99%

Induction of c-Fos-like and FosB-like immunoreactivity reveals forebrain neuronal populations involved differentially in pup-mediated maternal behavior in juvenile and adult rats

Kalinichev¹,

Rosenblatt²,

Nakabeppu³

et al. 2000

J. Comp. Neurol.

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Juvenile rats can exhibit maternal behavior after being exposed continuously to rat pups, a process called sensitization. Maternal behavior in juveniles is robust and is similar to adult maternal behavior (Mayer and Rosenblatt [1979] Dev. Psychobiol. 12:407–424; Gray and Chesley [684] J. Comp. Psychol. 98:91–99). In this study, immunocytochemical detection of the protein products of two immediate‐early genes, c‐fos and fosB, was used as a tool to identify forebrain neuronal populations involved in the maternal behavior of 27‐day‐old juvenile rats compared with 60‐day‐old adults. To sensitize them, rats were exposed continuously to foster pups. Once they were maternal, they were isolated from pups overnight, reexposed to pups for 2 hours, and then killed. Nonmaternal control animals also were isolated overnight and were either reexposed to pups for 2 hours or kept isolated from pups before killing. The lateral habenula (LH) was the only area in which both maternal juveniles and maternal adults had more c‐Fos‐immunoreactive (‐Ir) neurons compared with controls. In maternal adults, the number of neurons that expressed c‐Fos and FosB immunoreactivity increased in the medial preoptic area (MPO) and the ventral bed nucleus of the stria terminalis (BSTv), whereas the dorsal bed nucleus of the stria terminalis (BSTd) and the medial and cortical nuclei of the amygdala (MEA and COA, respectively) had increases only in the number of neurons that expressed c‐Fos immunoreactivity. In contrast, juveniles, whether or not they were maternal, had the same number of c‐Fos‐IR and FosB‐Ir neurons in all these areas. The adult‐like increase in the number of c‐Fos‐Ir neurons found in maternal juveniles suggests that the juvenile LH participates in the neural circuit that supports maternal behavior in an adult‐like manner. The lack of c‐fos or fosB induction in the MPO, BSTv, BSTd, COA, or MEA of maternal juveniles compared with maternal adults may reflect the immaturity of these brain regions in juvenile rats. Exactly what this immaturity consists of and when the responses of these regions become adult‐like remain to be determined. J. Comp. Neurol. 416:45–78, 2000. © 2000 Wiley‐Liss, Inc.

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“…Western blot analysis demonstrated that ER-ß antisense ODN decreased the protein expression of ER-ß in the periventricular region. A large number of studies 28 successfully investigated the neuroendocrine and behavioral effects of intracerebral administration of antisense ODN including antisense ODN for ER-a. 29,30 In the present study, specific effects of the antisense ODN for ER-ß were confirmed using two different sequences of antisense ODN and control sense and scrambled ODN.…”

Section: Er-b and Feeding Y-q Liang Et Almentioning

confidence: 99%

Estrogen receptor ß is involved in the anorectic action of estrogen

Akishita

et al. 2002

Int J Obes

142

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OBJECTIVE: Estrogen has been implicated in feeding behavior and adiposity. This study was undertaken to elucidate the mechanism underlying the anti-obesity and anorectic action of estrogen and the role of estrogen receptor (ER) in the central nervous system. METHODS AND RESULTS: Ovariectomy in 8-week-old female Wistar rats induced hyperphagia along with an increase in body weight and abdominal fat accumulation compared to control sham-operated rats. These changes were fully reversed by subcutaneous replacement of estradiol and were abrogated by pair-feeding. Then, the effects of intracerebroventricular infusion of estradiol, alone or in combination with antisense oligodeoxynucleotides (ODN), for ER in ovariectomized rats were examined. The estradiol group showed 10 -20% lower daily food intake, and after the 2-week infusion period a 14% reduction in body weight with a similar reduction in abdominal fat compared to the vehicle group. The inhibitory effect of estradiol on food intake and body weight was blocked by co-administration of ER-ß antisense ODN, whereas ER-a antisense ODN did not show any influence. CONCLUSION: These results indicate that ER-ß in the central nervous system is involved in the anorectic action of estrogen.

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Neuroendocrine and behavioral effects of antisense oligonucleotides

Cited by 21 publications

References 84 publications

Inhibition of Steroid Receptor Coactivator-1 Blocks Estrogen and Androgen Action on Male Sex Behavior and Associated Brain Plasticity

Inhibition of Steroid Receptor Coactivator-1 Blocks Estrogen and Androgen Action on Male Sex Behavior and Associated Brain Plasticity

Induction of c-Fos-like and FosB-like immunoreactivity reveals forebrain neuronal populations involved differentially in pup-mediated maternal behavior in juvenile and adult rats

Estrogen receptor ß is involved in the anorectic action of estrogen

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