Altering behavioral responses and dopamine transporter protein with antisense peptide nucleic acids 1 1Abbreviations: DAT, dopamine transporter; and PNA, peptide nucleic acid.

Tyler-McMahon, Beth M; Stewart, Jennifer A.; Jackson, Jordan E.; Bitner, M.D; Fauq, Abdul H.; McCormick, Daniel J.; Richelson, Elliott

doi:10.1016/s0006-2952(01)00698-0

Cited by 14 publications

(8 citation statements)

References 19 publications

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“…Psychostimulants such as cocaine and amphetamine act directly on the dopamine transporter (DAT), a NaCl-dependent membrane transporter that catalyzes the removal of dopamine from the synapse, resulting in reversal and/or inhibition of dopamine transport and increases in extracellular dopamine (Schenk, 2002; Sulzer et al, 1995). Predictably, alterations in DAT levels affect various cocaine- or amphetamine-induced behaviors in animals and humans (Dietz et al, 2005; Ritz et al, 1987; Silvia et al, 1997; Tyler-McMahon et al, 2001). …”

Section: Introductionmentioning

confidence: 99%

Time‐of‐day differences in dopamine clearance in the rat medial prefrontal cortex and nucleus accumbens

Sleipness

Jansen

Schenk

et al. 2008

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Circadian rhythms influence cocaine-seeking behavior in rats, and this behavior may be mediated by variability in the rate of extracellular dopamine clearance across the day:night cycle. We used rotating disk electrode voltammetry to examine dopamine clearance and inhibition of clearance by cocaine in the rat medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Rats were housed under light:dark conditions (LD, 12 hr:12 hr) or in constant darkness (DD), the latter given just prior to the day of sacrifice. Tissue was collected at 4 hr intervals under LD and DD conditions. Under LD, dopamine clearance in both brain regions was greatest at 4 hr after lights on. Under DD, there was a blunted but still rhythmic pattern of dopamine clearance across the 24 hr cycle. Cocaine-induced inhibition of dopamine clearance in the mPFC was not different across the day:night cycle in rats under LD. Paradoxically, under DD, dopamine clearance in the mPFC was enhanced by cocaine at ZT16, 4 hr into the subjective night, and only minimally inhibited at other times. In the NAc, cocaine inhibition of dopamine clearance was lowest at ZT4 under LD, and did not vary under DD. We conclude that dopamine clearance varies in both a diurnal and possibly in a circadian manner in the mPFC, and in a diurnal manner in the NAc. These results indicate that light itself may be used to manipulate molecules implicated in drug addiction.

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Section: Introductionmentioning

confidence: 99%

Time‐of‐day differences in dopamine clearance in the rat medial prefrontal cortex and nucleus accumbens

Sleipness

Jansen

Schenk

et al. 2008

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“…All PNAs were synthesized on a 50 mmol scale on PS_PEG_PALresin (PerSeptive Biosystems, Framingham, MA) as described (Tyler-McMahon et al, 2001). An aliquot of each synthesis was analyzed by ESI mass spectrometry and MALDI-TOF to confirm the molecular weight.…”

Section: Pna Synthesismentioning

confidence: 99%

Using peptide nucleic acids as gene-expression modifiers to reduce β-amyloid levels

et al. 2002

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The deposition of amyloid beta peptide (A beta) is an early and critical aspect of Alzheimer's disease. A beta is formed by the cleavage of amyloid precursor protein (APP). Studies of familial forms of Alzheimer's disease indicate that elevated secretion of A beta, particularly A beta(1-42), is likely to be an etiologic agent in the disease. A beta(1-42) is known to cause fibril formation and at elevated levels increases aggregation, which can lead to neuronal death. It has, therefore, been hypothesized that if the levels of A betaB, particularly A beta(1-42), could be reduced that onset of Alzheimer's disease could be slowed or possibly prevented. We, therefore, propose using PNAs targeted to APP to decrease plasma and brain levels of A beta(1-40) and A beta(1-42). This research project is designed to expand upon the discovery in our laboratory that systemic administration of antisense or antigene treatments utilizing peptide nucleic acids (PNAs) can be used to target and shut down proteins. Antisense strategies are methods of specifically targeting a particular protein by inhibiting translation by complementary binding to mRNA, while antigene methods inhibit transcription by complementary binding to DNA. For experiments involving antisense strategies, there are several advantages to using PNAs as opposed to the traditional oligonucleotide approaches. We initially preformed our studies in rats and identified a PNA sequence that was able to significantly reduce the levels of A beta(1-41) in rat brain compared to vehicle control rats. We have switched to mice so that we can prepare to perform our experiments in a transgenic animal model of Alzheimer's disease. We have, however, run into several technical difficulties with using mice compared to rats. In spite of this, we have identified one PNA sequence that specifically lowers mouse brain A beta(1-40) A beta(1-42) by 37% and 47%, respectively.

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“…25,46 They are highly resistant against cell nucleases, proteases and peptidases. 25,27,47 PNA oligomers undergo very slow enzymatic hydrolysis in both cell extracts and in vivo. 25,46 PNA molecules are distinguished by generally low toxicity and are not prone to non-specific binding to cellular proteins.…”

Section: Properties Of Peptide Nucleic Acidsmentioning

confidence: 99%

“…Antisense PNA selectively inhibit the expression of brain proteins. 47 The design of anticancer and antiviral drugs based on PNA seems to be a very promising approach. 26,57,65 Some PNA derivatives manifest antibacterial 36 and antisense activities 9,47 towards eukaryotic cells and animal organisms.…”

Section: Applications Of Peptide Nucleic Acidsmentioning

confidence: 99%

“…47 The design of anticancer and antiviral drugs based on PNA seems to be a very promising approach. 26,57,65 Some PNA derivatives manifest antibacterial 36 and antisense activities 9,47 towards eukaryotic cells and animal organisms. 9,47 There is evidence that PNA interfere with all the key stages of gene expression.…”

Section: Applications Of Peptide Nucleic Acidsmentioning

confidence: 99%

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Peptide nucleic acids: structure, properties, applications, strategies and practice of chemical synthesis

Antsypovitch¹

2002

Russ. Chem. Rev.

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The information on the structure and properties of The information on the structure and properties of peptide nucleic acids (PNA) is generalised. The use of PNA peptide nucleic acids (PNA) is generalised. The use of PNA oligomers in biomolecular studies and biotechnology is exempli-oligomers in biomolecular studies and biotechnology is exemplified. The published data on the most important methods for the fied. The published data on the most important methods for the chemical synthesis of PNA oligomers with the main emphasis on chemical synthesis of PNA oligomers with the main emphasis on the efficiency of condensation reactions are considered. The the efficiency of condensation reactions are considered. The methods for PNA synthesis are systematised; their advantages methods for PNA synthesis are systematised; their advantages and disadvantages are discussed. Some recommendations for and disadvantages are discussed. Some recommendations for optimisation of the condensation procedure and synthesis of optimisation of the condensation procedure and synthesis of PNA are presented. The bibliography includes 153 references PNA are presented. The bibliography includes 153 references. .

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Altering behavioral responses and dopamine transporter protein with antisense peptide nucleic acids 1 1Abbreviations: DAT, dopamine transporter; and PNA, peptide nucleic acid.

Cited by 14 publications

References 19 publications

Time‐of‐day differences in dopamine clearance in the rat medial prefrontal cortex and nucleus accumbens

Time‐of‐day differences in dopamine clearance in the rat medial prefrontal cortex and nucleus accumbens

Using peptide nucleic acids as gene-expression modifiers to reduce β-amyloid levels

Peptide nucleic acids: structure, properties, applications, strategies and practice of chemical synthesis

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