Effect of externally added carnitine on the synthesis of acetylcholine in rat cerebral cortex cells

Wawrzenczyk, A.; Nałęcz, Katarzyna A.; Nałȩcz, Maciej J.

doi:10.1016/0197-0186(94)00162-n

Cited by 33 publications

(34 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because the initial rates of transport were similar in both strains, up to 10 min of incubation, we hypothesized that the late differences in transport of ␣-KIC could be due to differences in metabolic rates in the two strains. Thus, we used membrane vesicles isolated from cortical neurons of GAERS or NE rats to measure the transport and accumulation of [ 14 C]␣-KIC without any metabolic influence, because the mitochondrial and cytoplasmic fractions are discarded to perform these experiments (Wawrzenczyk et al, 1995). We observed a 30-fold higher accumulation of [ 14 C]␣-KIC in vesicles than in intact neurons.…”

Section: Transport Of ␣-Kic Into Cortical Neurons Points To a Metabolmentioning

confidence: 92%

“…The integrity of the cells was controlled by means of the trypan blue test (0.5% in saline). This neuronal preparation contains mostly neurons, as verified by the presence of gammaenolase and GABA transporter GAT1 (Wawrzenczyk et al, 2001), whereas no astroglial markers, such as glial fibrillary acidic protein (GFAP; Wawrzenczyk et al, 2001) and carbonic anhydrase (Wawrzenczyk et al, 1995), were detected.…”

Section: Accumulation Of ␣-Kic In Acutely Isolated Cortical Neuronsmentioning

confidence: 98%

“…White matter and pial membranes were carefully discarded, and cortical cells were dispersed at 37°C by dispase digestion. Cerebral cortical neurons were isolated from GAERS and NE rat brains by using spinning, filtrating, and density gradient techniques (with dextran), according to techniques previously described in detail (Wawrzenczyk et al, 1995;Mac et al, 2000). The integrity of the cells was controlled by means of the trypan blue test (0.5% in saline).…”

Section: Accumulation Of ␣-Kic In Acutely Isolated Cortical Neuronsmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic approach of absence seizures in a genetic model of absence epilepsy, the GAERS: Study of the leucine‐glutamate cycle

Dufour

Nałęcz

Nałȩcz

et al. 2001

J of Neuroscience Research

View full text Add to dashboard Cite

We suggest that a dysregulation of energy metabolism in the brain of genetic absence epilepsy rats from Strasbourg (GAERS) could create a specific cerebral environment that would favor the expression of spike-and-wave discharges (SWD) in the thalamocortical loop, largely dependent on glutamatergic and gamma-aminobutyric acid (GABA)-ergic neurotransmissions. We tested several aspects of metabolic activity in the brain of GAERS compared to a genetic strain of nonepileptic (NE) rats. Glucose metabolism was higher in all brain regions of GAERS compared to those of NE rats along the whole glycolytic and aerobic pathways, as assessed by regional histochemical measurement of lactate dehydrogenase and cytochrome oxidase activities. Branched-chain amino acids (BCAA) and alpha-ketoisocaproate (alpha-KIC), the ketoacid of leucine, when injected intraperitoneally, increased the number of SWD in GAERS but had only a slight effect on their duration. These data speak in favor of a BCAA- or alpha-KIC-induced change in neuronal excitability. Leucine and alpha-KIC decreased the concentration of glutamate in thalamus and cortex without affecting GABA concentrations. Thus, BCAA and alpha-KIC, by decreasing glutamatergic neurotransmission, could favor GABAergic neurotransmission, which is known to increase the occurrence of seizures in GAERS. Finally, the transport of [1-(14)C]alpha-KIC in freshly isolated cortical neurons was lower in GAERS than in NE rats, and this difference was shown to be of metabolic origin. The addition of gabapentin, a specific inhibitor of BCAA transaminase (BCAT), reduced the transport of [1-(14)C]alpha-KIC in GAERS and NE rats to a level that became identical in both strains. This strain-dependent change was not related to a difference in the activity of BCAT, which was identical in GAERS and NE rats. The exact origin of this apparent metabolic dysregulation of energy metabolism in GAERS that could underlie the origin of seizures in that strain remains to be explored further.

show abstract

Section: Transport Of ␣-Kic Into Cortical Neurons Points To a Metabolmentioning

confidence: 92%

Section: Accumulation Of ␣-Kic In Acutely Isolated Cortical Neuronsmentioning

confidence: 98%

Section: Accumulation Of ␣-Kic In Acutely Isolated Cortical Neuronsmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic approach of absence seizures in a genetic model of absence epilepsy, the GAERS: Study of the leucine‐glutamate cycle

Dufour

Nałęcz

Nałȩcz

et al. 2001

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…ALCAR is also expected to be beneficial for cerebral symptoms such as those of Alzheimer's disease and depression among the geriatric population [2,8]. Despite studies on the long-term supply of high-dose ALCAR, its effects are obscure [3,9,10].…”

Section: Introductionmentioning

confidence: 98%

Acetyl‐L‐carnitine permeability across the blood–brain barrier and involvement of carnitine transporter OCTN2

Inano

Sai

Nikaido

et al. 2003

Biopharm & Drug Disp

View full text Add to dashboard Cite

OCTN2 (SLC22A5), an organic cation/carnitine transporter, is widely distributed throughout the body, including the brain. In the present study, the involvement of OCTN2 in acetyl-L-carnitine (ALCAR) permeation across the blood-brain barrier (BBB) was examined using a microdialysis method in mouse. OCTN2 function was examined by comparison of wild-type mice with jvs mice, which express defective OCTN2 and are considered a model for primary systemic carnitine deficiency. Zero-net-flux method analysis indicated higher in vivo recovery of ALCAR and lower physiological ALCAR concentration in thalamus extracellular fluid (ECF) in jvs mice compared with wild-type mice. Externally added ALCAR showed significantly slower initial uptake across the BBB in jvs mouse. These results indicated that OCTN2 is functionally involved in ALCAR transfer across the BBB. Total radioactivity in ECF after i.v. administration of radiolabelled ALCAR remained constant for the rest of the experimental period. Accordingly, our results indicate that ALCAR is transported from blood to brain ECF by OCTN2 at least in part, and its concentration in brain ECF is regulated by other events such as protein binding and anabolic reactions in the brain, as well as by transport across the BBB.

show abstract

“…Foreman et al [87] reported that ALCAR exerted a neuroprotective action on central cholinergic neurons at the level of transcription of the low-affi nity nerve growth factor receptor p75 NGFR . Wawrzenczyk et al [88] and Gorini et al [89] showed that ALCAR increased acetylcholine synthesis.…”

Section: L-carnitinementioning

confidence: 99%

Beneficial Effects of Dietary Vitamins, Lipoic Acid and Carnitine on the Aging Brain

Ng¹,

Ye²

2004

Neuroembryol Aging

View full text Add to dashboard Cite

show abstract

Effect of externally added carnitine on the synthesis of acetylcholine in rat cerebral cortex cells

Cited by 33 publications

References 38 publications

Metabolic approach of absence seizures in a genetic model of absence epilepsy, the GAERS: Study of the leucine‐glutamate cycle

Metabolic approach of absence seizures in a genetic model of absence epilepsy, the GAERS: Study of the leucine‐glutamate cycle

Acetyl‐L‐carnitine permeability across the blood–brain barrier and involvement of carnitine transporter OCTN2

Beneficial Effects of Dietary Vitamins, Lipoic Acid and Carnitine on the Aging Brain

Contact Info

Product

Resources

About