Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation.

Sacktor, Todd Charlton; Osten, Pavel; Valsamis, Helen; Jiang, Xiaolan; Naik, Meghna U.; Sublette, Elizabeth

doi:10.1073/pnas.90.18.8342

Cited by 396 publications

(332 citation statements)

References 34 publications

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“…Tissue was homogenized in a Tris buffer containing a cocktail of protease inhibitors (Sacktor et al, 1993). After low speed centrifugation to remove particulates (5 min at 3,000 g), the supernatant underwent ultracentrifugation (30 min at 100,000 g) and this resulting supernatant reflected the cytosol.…”

Section: Hippocampal Protein Isolationmentioning

confidence: 99%

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

2008

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Prenatal exposure to opiates, which is invariably followed by postnatal withdrawal, can affect cognitive performance. To further characterize these effects, we examined radial 8-arm maze performance and expression of brain derived neurotrophic factor (BDNF) in male rats prenatally exposed to the opiate l-α-acetylmethadol (LAAM). Female rats received 1.0 mg/kg/day LAAM or water via daily oral gavage for 28 days prior to breeding, during breeding, and throughout pregnancy. Pups were fostered to non-treated lactating dams at birth and underwent neonatal opiate withdrawal. At 5-6 months, prenatal water-and LAAM-exposed males (n=6 each; non-littermates) received radial arm maze training consisting of ten trials a day for five days and three retention trials on day six. Rats prenatally exposed to LAAM had poorer maze performance, decreased percent correct responding and more reference and working memory errors than prenatal water-treated controls. However, they were able to acquire the task by the end of training. There were no differences between the groups on retention 24 hr after testing. Following retention testing, hippocampi were removed and protein extracted from cytosol and synaptic fractions. Western blots were used to measure levels of mature and precursor BDNF protein, as well as the BDNF receptor TrkB. BDNF precursor protein was significantly decreased in the synaptic fraction of trained prenatal LAAM-treated rats compared to prenatal water-treated trained controls. No effects were found for the full-length or truncated TrkB receptor. In untrained rats, prenatal treatment did not affect any of the measures. These data suggest that prenatal opiate exposure and/or postnatal withdrawal compromise expression of proteins involved in the neural plasticity underlying learning.

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Section: Hippocampal Protein Isolationmentioning

confidence: 99%

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

2008

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“…This is notable because persistent activation of PKC has been shown to be associated with and necessary for the expression of LTP (Klann et al, 1991(Klann et al, , 1993Wang and Feng, 1992;Sacktor et al, 1993;Hrabetova and Sacktor, 1996).…”

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confidence: 99%

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

Knapp¹,

2002

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Recent evidence suggests that reactive oxygen species (ROS), including superoxide, are not only neurotoxic but function as small messenger molecules in normal neuronal processes such as synaptic plasticity. Consistent with this idea, we show that brief incubation of hippocampal slices with the superoxidegenerating system xanthine/xanthine oxidase (X/XO) produces a long-lasting potentiation of synaptic transmission in area CA1. We found that X/XO-induced potentiation was associated with a persistent superoxide-dependent increase in autonomous PKC activity that could be isolated via DEAE column chromatography. The X/XO-induced potentiation was blocked by the inhibition of PKC, indicating that the superoxidedependent increase in autonomous PKC activity was necessary for the potentiation. We also found that X/XO-induced potentiation and long-term potentiation (LTP) occluded one another, suggesting that these forms of plasticity share similar cellular mechanisms. In further support of this idea, we found that a persistent, superoxide-dependent increase in autonomous PKC activity isolated via DEAE column chromatography also was associated with LTP. Taken together, our findings indicate that X/XO-induced potentiation and LTP share similar cellular mechanisms, including superoxide-dependent increases in autonomous PKC activity. Finally, our findings suggest that superoxide, in addition to its well known role as a neurotoxin, also can be considered a small messenger molecule critical for normal neuronal signaling.

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“…In the brain, PKC's are highly concentrated and have been implicated in a broad spectrum of neuronal functions, such as modulation of ion channels [4], receptors [5] and neurotransmitter release [6]. PKC activation has also been implicated in the initiation and maintenance of Long Term Potentiation (LTP) [7,8] and Long Term Depression (LTD) [9].…”

Section: Introductionmentioning

confidence: 99%

Expression of protein kinase C isozymes in hippocampal neurones in culture

1995

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Several protein kinase C (PKC) isozymes were analyzed by immunoblot and immunocytochemistry in cultures of hippocampal neurones at several stages of differentiation. Our findings reveal the existence of two distinct patterns of expression. Firstly, conventional PKC isozymes a, /3 and % that are expressed at very low levels during the initial stages and then increase continuously with time of culture. Secondly, novel PKC isozymes 6, ~ and 5, whose contents increase very early to reach a maximum after three days of culture and then progressively decline. Specific proteolysis for PKC isozymes i~ and y was observed throughout the period studied. The developmental profile obtained for the different PKC isozymes is discussed in relation to the differentiation of hippocampal neurones in culture.

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Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation.

Cited by 396 publications

References 34 publications

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

Expression of protein kinase C isozymes in hippocampal neurones in culture

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