Activity In Rat Cerebral Cortex Research Articles

SkQ1 Controls CASP3 Gene Expression and Caspase-3-Like Activity in the Brain of Rats under Oxidative Stress.

Here, we studied the effect of the mitochondria-targeted antioxidant SkQ1 (plastoquinone cationic derivative) on the CASP3 gene expression and caspase-3 activity in rat cerebral cortex and brain mitochondria under normal conditions and in oxidative stress induced by hyperbaric oxygenation (HBO). Under physiological conditions, SkQ1 administration (50 nmol/kg, 5 days) did not affect the CASP3 gene expression and caspase-3-like activity in the cortical cells, as well as caspase-3-like activity in brain mitochondria, but caused a moderate decrease in the content of primary products of lipid peroxidation (LPO) and an increase in the reduced glutathione (GSH) level. HBO-induced oxidative stress (0.5 MPa, 90 min) was accompanied by significant upregulation of CASP3 mRNA and caspase-3-like activity in the cerebral cortex, activation of the mitochondrial enzyme with simultaneous decrease in the GSH content, increase in the glutathione reductase activity, and stimulation of LPO. Administration of SkQ1 before the HBO session maintained the basal levels of the CASP3 gene expression and enzyme activity in the cerebral cortex cells and led to the normalization of caspase-3-like activity and redox parameters in brain mitochondria. We hypothesize that SkQ1 protects brain cells from the HBO-induced oxidative stress due to its antioxidant activity and stimulation of antiapoptotic mechanisms.

Tualang Honey Reduced Neuroinflammation and Caspase-3 Activity in Rat Brain after Kainic Acid-Induced Status Epilepticus.

The protective effect of tualang honey (TH) on neuroinflammation and caspase-3 activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA-) induced status epilepticus was investigated. Male Sprague-Dawley rats were pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA (15 mg/kg body weight) was injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Neuroinflammation markers and caspase-3 activity were analyzed in different brain regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced epileptic seizures. KA caused significant (p < 0.05) increase in the level of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment with TH significantly (p < 0.05) reduced the elevation of TNF-α, IL-1β, GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and attenuated the increased caspase-3 activity in the cerebral cortex. In conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid- (KA-) induced status epilepticus.

Hyperthermia-induced seizures alter adenosine A1 and A2A receptors and 5'-nucleotidase activity in rat cerebral cortex.

Febrile seizure is one of the most common convulsive disorders in children. The neuromodulator adenosine exerts anticonvulsant actions through binding adenosine receptors. Here, the impact of hyperthermia-induced seizures on adenosine A1 and A2A receptors and 5'-nucleotidase activity has been studied at different periods in the cerebral cortical area by using radioligand binding, real-time PCR, and 5'-nucleotidase activity assays. Hyperthermic seizures were induced in 13-day-old rats using a warmed air stream from a hair dryer. Neonates exhibited rearing and falling over associated with hindlimb clonus seizures (stage 5 on Racine scale criteria) after hyperthermic induction. A significant increase in A1 receptor density was observed using [(3) H]DPCPX as radioligand, and mRNA coding A1 was observed 48h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density was detected, using [(3) H]ZM241385 as radioligand, 48h after hyperthermia-evoked convulsions. These short-term changes in A1 and A2A receptors were also accompanied by a loss of 5'-nucleotidase activity. No significant variations either in A1 or A2A receptor density or 5'-nucleotidase were observed 5 and 20days after hyperthermic seizures. Taken together, both regulation of A1 and A2A receptors and loss of 5'-nucleotidase in the cerebral cortex suggest the existence of a neuroprotective mechanism against seizures. Febrile seizure is one of the most common convulsive disorders in children. The consequences of hyperthermia-induced seizures (animal model of febrile seizures) on adenosine A1 and A2A receptors and 5'-nucleotidase activity have been studied at different periods in cerebral cortical area. A significant increase in A1 receptor density and mRNA coding A1 was observed 48h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density and 5'-nucleotidase activity was detected 48h after convulsions evoked by hyperthermia. These changes suggest the possible existence of a neuroprotective mechanism against seizures.

Spatial patterns of neuronal activity in rat cerebral cortex during non-rapid eye movement sleep.

It is commonly assumed that cortical activity in non-rapid eye movement sleep (NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to the limited observational scope of common metabolic or imaging methods in sleep. We used the recently developed technique of thallium-autometallography (TlAMG) to visualize mesoscopic patterns of activity in the sleeping cortex with single-cell resolution. We intravenously injected rats with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC) during spontaneously occurring periods of NREMS and mapped the patterns of neuronal uptake of the potassium (K+) probe thallium (Tl+). Using this method, we show that cortical activity patterns are not spatially homogeneous during discrete 5-min episodes of NREMS in unrestrained rats—rather, they are complex and spatially diverse. Along with a relative predominance of infragranular layer activation, we find pronounced differences in metabolic activity of neighboring neuronal assemblies, an observation which lends support to the emerging paradigm that sleep is a distributed process with regulation on the local scale.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-014-0867-9) contains supplementary material, which is available to authorized users.

A method for reconstructing tomographic images of evoked neural activity with electrical impedance tomography using intracranial planar arrays

A method is presented for reconstructing images of fast neural evoked activity in rat cerebral cortex recorded with electrical impedance tomography (EIT) and a 6 × 5 mm2 epicortical planar 30 electrode array. A finite element model of the rat brain and inverse solution with Tikhonov regularization were optimized in order to improve spatial resolution and accuracy. The optimized FEM mesh had 7 M tetrahedral elements, with finer resolution (0.05 mm) near the electrodes. A novel noise-based image processing technique based on t-test significance improved depth localization accuracy from 0.5 to 0.1 mm. With the improvements, a simulated perturbation 0.5 mm in diameter could be localized in a region 4 × 5 mm2 under the centre of the array to a depth of 1.4 mm, thus covering all six layers of the cerebral cortex with an accuracy of <0.1 mm. Simulated deep brain hippocampal or thalamic activity could be localized with an accuracy of 0.5 mm with a 256 electrode array covering the brain. Parallel studies have achieved a temporal resolution of 2 ms for imaging fast neural activity by EIT during evoked activity; this encourages the view that fast neural EIT can now resolve the propagation of depolarization-related fast impedance changes in cerebral cortex and deeper in the brain with a resolution equal or greater to the dimension of a cortical column.

Disruption of redox homeostasis and brain damage caused in vivo by methylmalonic acid and ammonia in cerebral cortex and striatum of developing rats

Hyperammonemia is a common finding in children with methylmalonic acidemia and propionic acidemia, but its contribution to the development of the neurological symptoms in the affected patients is poorly known. Considering that methylmalonic acid (MMA) and propionic acid (PA) predominantly accumulate in these disorders, we investigated the effects of hyperammonemia induced by urease treatment in 30-day-old rats receiving an intracerebroventricular (ICV) injection of MMA or PA on important parameters of redox homeostasis in cerebral cortex and striatum. We evaluated glutathione (GSH) concentrations, sulfhydryl content, nitrate and nitrite concentrations, 2′,7′-dichlorofluorescein (DCFH) oxidation, and the activity of antioxidant enzymes. MMA decreased GSH concentrations and sulfhydryl content and increased nitrate and nitrite concentrations in cerebral cortex and striatum from hyperammonemic rats, whereas MMA or ammonia per se did not alter these parameters. MMA plus hyperammonemia also decreased glutathione reductase activity in rat cerebral cortex, but did not affect catalase, superoxide dismutase and glutathione peroxidase activities, neither DCFH oxidation. Furthermore, ICV PA administration alone or combined with hyperammonemia did not alter any of the evaluated parameters. We also found that pre-treatment with antioxidants prevented GSH reduction and sulfhydryl oxidation, whereas Nω-nitro-L-arginine methyl ester (L-NAME) prevented the increased nitrate and nitrite concentrations provoked by MMA plus ammonia treatments. Histological alterations, including vacuolization, ischemic neurons, and pericellular edema, were observed in brain of hyperammonemic rats injected with MMA. The data indicate a synergistic effect of MMA and ammonia disturbing redox homeostasis and causing morphological brain abnormalities in rat brain.

Inhibition of noradrenaline release from cerebrocortical synaptosomes and stimulation of synaptosomal Na+, K+-ATPase activity by morphine in rats

The effects of morphine on noradrenaline (NA) release from rat cerebrocortical synaptosomes and on the synaptosomal Na+,K(+)-ATPase activity were determined. Morphine (10(-3)-10(-5) M) caused a dose-related inhibition of enhanced prelabelled [3H]NA release evoked by a high concentration of K+ from synaptosomes and this inhibitory action of morphine was antagonized by the specific antagonist naloxone (10(-4), 10(-5) M). Morphine dose-dependently stimulated the synaptosomal Na+,K(+)-ATPase activity but not Ca2(+)-ATPase activity in the incubation medium containing 2.2 x 10(-6)-4.7 x 10(-7) M free Ca2+, and this stimulatory effect was antagonized by naloxone. These results suggest that morphine may have some role in the suppression of membrane depolarization and/or the release of NA through its stimulatory action on the Na+,K(+)-ATPase activity in rat cerebral cortex.

In vitro evidence that d-serine disturbs the citric acid cycle through inhibition of citrate synthase activity in rat cerebral cortex

The present work investigated the in vitro effects of d-serine ( d-Ser) on important parameters of energy metabolism in cerebral cortex of young rats. The parameters analyzed were CO 2 generation from glucose and acetate, glucose uptake and the activities of the respiratory chain complexes I–IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogense, fumarase and malate dehydrogenase and of creatine kinase and Na +,K +-ATPase. Our results show that d-Ser significantly reduced CO 2 production from acetate, but not from glucose, reflecting an impairment of the citric acid cycle function. Furthermore, d-Ser did not affect glucose uptake. We also observed that the activity of the mitochondrial enzyme citrate synthase from mitochondrial preparations and purified citrate synthase was significantly inhibited by d-Ser, whereas the other activities of the citric acid cycle as well as the activities of complexes I–III, II–III, II and IV of the respiratory chain, creatine kinase and Na +,K +-ATPase were not affected by this d-amino acid. We also found that l-serine did not affect citrate synthase activity from mitochondrial preparations and purified enzyme. The data indicate that d-Ser impairs the citric acid cycle activity via citrate synthase inhibition, therefore compromising energy metabolism production in cerebral cortex of young rats. Therefore, it is presumed that this mechanism may be involved at least in part in the neurological damage found in patients affected by disorders in which d-Ser metabolism is impaired, with altered cerebral concentrations of this d-amino acid.

Spatial patterns of neuronal activity in rat cerebral cortex during slow-wave sleep - a single-cell resolution metabolic mapping study

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Hypermethioninemia Increases Cerebral Acetylcholinesterase Activity and Impairs Memory in Rats

In the present study we investigated the effect of chronic hypermethioninemia on rat performance in the Morris water maze task, as well as on acetylcholinesterase (AChE) activity in rat cerebral cortex. For chronic treatment, rats received subcutaneous injections of methionine (1.34-2.68 micromol/g of body weight), twice a day, from the 6th to the 28th day of age; control rats received the same volume of saline solution. Groups of rats were killed 3 h, 12 h or 30 days after the last injection of methionine to AChE assay and another group was left to recover until the 60th day of life to assess the effect of early methionine administration on reference and working spatial memory of rats. AChE activity was also determined after behavioral task. Results showed that chronic treatment with methionine did not alter reference memory when compared to saline-treated animals. In the working memory task, we observed a significant days effect with significant differences between control and methionine-treated animals. Chronic hypermethioninemia significantly increased AChE activity at 3 h, 12 h or 30 days after the last injection of methionine, as well as before or after behavioral test. The effect of acute hypermethioninemia on AChE was also evaluated. For acute treatment, 29-day-old rats received one single injection of methionine (2.68 micromol/g of body weight) or saline and were killed 1, 3 or 12 h later. Results showed that acute administration of methionine did not alter cerebral cortex AChE activity. Our findings suggest that chronic experimental hypermethioninemia caused cognitive dysfunction and an increase of AChE activity that might be related, at least in part, to the neurological problems presented by hypermethioninemic patients.

Proline reduces brain cytochrome c oxidase: prevention by antioxidants

In the present study, we initially investigated the in vivo (acute and chronic) and in vitro effects of proline on cytochrome c oxidase (complex IV) activity in rat cerebral cortex to test the hypothesis that proline might alter energy metabolism and that this alteration could be provoked by oxidative stress. The action of α-tocopherol and ascorbic acid on the effects produced by proline was also evaluated. For acute administration, 29- and 60-day-old rats received one subcutaneous injection of proline (18.2μmol/gbodyweight) or an equivalent volume of 0.9% saline solution (control) and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously twice a day at 10h intervals from the 6th to the 28th day of age. Rats were sacrificed 12h (29th) or 31 days (60th) after the last injection. Results showed that acute administration of proline significantly diminished the activity of cytochrome c oxidase in the cerebral cortex of 29- and 60-day-old rats. On the other hand, chronic hyperprolinemia reduced this complex activity only on day 29, but not on the 60th day of life. In another set of experiments, 22-day-old rats or 53-day-old rats were pretreated for 1 week with daily intraperitoneal administration of α-tocopherol (40mg/kg) and ascorbic acid (100mg/kg) or saline. Twelve hours after the last antioxidant injection, rats received a single injection of proline or saline and were killed 1h later. In parallel to chronic treatment, rats received a daily intraperitoneal injection of α-tocopherol and ascorbic acid from the 6th to the 28th day of life and were killed 12h after the last injection. Results showed that the pretreatment with α-tocopherol and ascorbic acid before acute proline administration or concomitant to chronic proline administration significantly prevented these effects. We also observed that proline (3.0μM–1.0mM) when added to the incubation medium (in vitro studies) did not alter cytochrome c oxidase activity. Data suggest that the inhibitory effect of proline on cytochrome c oxidase activity is possibly associated with oxidative stress and that this parameter may be involved in the brain dysfunction observed in hyperprolinemia.

Fos expression and task-related neuronal activity in rat cerebral cortex after instrumental learning

Learning has been shown to induce changes in neuronal gene expression and to produce development of task-specific neuronal activity. The connection between these two features of neuronal plasticity remains of a great interest. To address this issue we compared distribution of c-Fos expressing and task-related neurons in the rat cerebral cortex following instrumental learning of appetitive lever-press task. The number of Fos-positive neurons was determined immunohistochemically in the retrosplenial and the motor cortex of naive (“control” group), newly trained (“acquisition” group) and overtrained (“performance” group) animals. A significant activation of c-Fos expression was observed in the neurons of the retrosplenial but not motor cortex in the “acquisition” group rats, as compared with the “control” and “performance” groups. In accordance with this c-Fos expression difference, the retrosplenial cortex of the trained animals contained significantly more neurons with lever-press-related activity than the motor cortex. Therefore, the two examined cortical areas showed a parallel between experience-dependent induction of c-Fos and development of task-related neuronal activity. These data support a notion that learning-induced activation of c-Fos is associated with long-term neurophysiological changes produced by training.

Effect of thuringiensin on adenylate cyclase in rat cerebral cortex

The purpose of this work is to evaluate the effect of thuringiensin on the adenylate cyclase activity in rat cerebral cortex. The cyclic adenosine 3′5′-monophosphate (cAMP) levels were shown to be dose-dependently elevated 17–450% or 54–377% by thuringiensin at concentrations of 10 μM–100 mM or 0.5–4 mM, due to the activation of basal adenylate cyclase activity of rat cerebral cortical membrane preparation. Thuringiensin also activated basal activity of a commercial adenylate cyclase from Escherichia coli. However, the forskolin-stimulated adenylate cyclase activity in rat cerebral cortex was inhibited by thuringiensin at concentrations of 1–100 μM, thus cAMP production decreased. Furthermore, thuringiensin or adenylate cyclase inhibitor (MDL-12330A) reduced the forskolin (10 μM)-stimulated adenylate cyclase activity at concentrations of 10 μM, 49% or 43% inhibition, respectively. In conclusion, this study demonstrated that thuringiensin could activate basal adenylate cyclase activity and increase cAMP concentrations in rat cerebral cortex or in a commercial adenylate cyclase. Comparing the dose-dependent effects of thuringiensin on the basal and forskolin-stimulated adenylate cyclase activity, thuringiensin can be regarded as a weak activator of adenylate cyclase or an inhibitor of forskolin-stimulated adenylate cyclase.

Proline reduces acetylcholinesterase activity in cerebral cortex of rats.

In the present study we investigated the in vivo and in vitro effect of proline (Pro) on acetylcholinesterase (AChE) activity in rat cerebral cortex. The action of vitamins E and C on the effects produced by Pro was also tested. Twelve-day-old rats received one s.c. injection of Pro (12.8 micromol/g body weight) or an equivalent volume of 0.9% saline solution (control) and were killed 1 h later. In another set of experiments, 5-day-old rats were pretreated for 1 week with daily i.p. administration of saline (control) or vitamins E (40 mg/kg) and C (100 mg/kg). Twelve hours after the last injection the rats received one s.c. injection of Pro (12.8 micromol/g body weight) or saline (control) and were killed 1 h later. For the in vitro studies, cerebral cortex homogenates of 12-day-old untreated rats were incubated for 1 h with various concentrations of Pro (3.0 microM-1.0 mM) or with 1.0 mM Pro, 1.0 mM trolox, or 1.0 mM Pro plus 1.0 mM trolox. Controls did not contain Pro in the incubation medium. Our results showed that the AChE activity significantly decreased (25%) in rat brain subjected to Pro administration and that the pretreatment with vitamins E and C prevented this effect. Furthermore, Pro (0.5 and 1.0 mM) also inhibits AChE activity in vitro and trolox prevented this effect. The data suggest that the inhibitory effect of Pro on AChE activity is associated with oxidative stress. Although it is difficult to extrapolate our findings to the human condition, our results may be relevant to explain, at least in part, the neurologic dysfunction associated with hyperprolinemia type II.

Inhibition of cytochrome c oxidase activity in rat cerebral cortex and human skeletal muscle by d-2-hydroxyglutaric acid in vitro

l-2-Hydroxyglutaric (LGA) and d-2-hydroxyglutaric (DGA) acids are the characteristic metabolites accumulating in the neurometabolic disorders known as l-2-hydroxyglutaric aciduria and d-2-hydroxyglutaric aciduria, respectively. Although these disorders are predominantly characterized by severe neurological symptoms, the neurotoxic mechanisms of brain damage are virtually unknown. In this study we have evaluated the role of LGA and DGA at concentrations ranging from 0.01 to 5.0 mM on various parameters of energy metabolism in cerebral cortex slices and homogenates of 30-day-old Wistar rats, namely glucose uptake, CO 2 production and the respiratory chain enzyme activities of complexes I to IV. DGA significantly decreased glucose utilization (2.5 and 5.0 mM) by brain homogenates and CO 2 production (5 mM) by brain homogenates and slices, whereas LGA had no effect on either measurement. Furthermore, DGA significantly inhibited cytochrome c oxidase activity (complex IV) (EC 1.9.3.1) in a dose-dependent manner (35–95%) at doses as low as 0.5 mM, without compromising the other respiratory chain enzyme activities. In contrast, LGA did not interfere with these activities. Our results suggest that the strong inhibition of cytochrome c oxidase activity by increased levels of DGA could be related to the neurodegeneration of patients affected by d-2-hydroxyglutaric aciduria.

Assay of cyclic nucleotide phosphodiesterase activity in rat brain by high-performance liquid chromatography using (3,4-dimethoxyphenyl)glyoxal as a fluorescence derivatizing reagent

A selective and sensitive HPLC measurement of 3′,5′-cyclic nucleotide phosphodiesterase (PDE; EC 3.1.4.17) activity in rat cerebral cortex is described using (3,4-dimethoxyphenyl)glyoxal (DMPG) as a fluorogenic reagent for guanine and its nucleosides and nucleotides. cGMP, a substrate of PDE, and GMP, which was produced by the enzyme reaction, are selectively converted with DMPG to the fluorescent derivatives. The derivatives were separated by reversed-phase HPLC. The Michaelis constant for cGMP was obtained with homogenates of cerebral cortex as 9.8 μM, and the limits of detection at a signal-to-noise ratio of 3 of GMP were 50 fmol on the column. More than 0.5 pmol min −1 mg −1 protein of PDE activity can be measured.

Effects of lead on adenylate cyclase activity in rat cerebral cortex.

Lead decreased in a dose dependent manner the basal AC activity in membranes of rat cerebral cortex (IC50 = 2.5 +/- 0.1 microM). In membranes preincubated under basal conditions, AC activity was stimulated by approximately two and fourfold by 10 microM Gpp(NH)p or forskolin, respectively. Under basal conditions, lead (3 microM) inhibited enzyme activity up to 50%, but was not able to inhibit the Gpp(NH)p- or the forskolin-stimulated AC activity. However, in membranes preincubated with Gpp(NH)p (10 microM), lead (3 microM) had no significant effect on enzyme activity, but it partly blocked the stimulation of AC activity elicited by forskolin (10 microM). In membranes preincubated with 10 microM lead, the addition of 10 microM Gpp(NH)p or forskolin in the incubation medium did not stimulate AC activity. However, when added together in the incubation medium Gpp(NH)p + forskolin produced an increase in enzyme activity. In membranes preincubated with 10 microM lead + 10 microM Gpp(NH)p, Gpp(NH)p (10 microM) or forskolin (10 microM) added alone or in combination to the incubation medium did not stimulate AC activity. Moreover, under these latter conditions lead had no further effect on enzyme activity. These results indicate that lead may interact with G-proteins and with the catalytic subunit of cerebral cortical AC to produce inhibition of the enzyme activity.

β-Amyloid-Induced Cholinergic Denervation Correlates with Enhanced Nitric Oxide Synthase Activity in Rat Cerebral Cortex: Reversal by NMDA Receptor Blockade

Ample experimental evidence indicates that acute β-amyloid infusion into the nucleus basalis of rats elicits abrupt degeneration of the magnocellular cholinergic neurons projecting to the cerebral cortex. In fact, involvement of a permanent Ca 2+ overload, partially via N -methyl- d-aspartate (NMDA) receptors, was proposed as a pivotal mechanism in β-amyloid-induced neurodegeneration. A definite measure of NMDA receptor-mediated processes and subsequent Ca 2+ entry is the induction of Ca 2+/calmodulin-activated neuronal nitric oxide synthase ( n NOS) in nerve cells. In the present account we therefore assessed activation of n NOS in correlation with cholinergic decline after β-amyloid (1–42) or β-amyloid (25–35) infusion into the rat nucleus basalis. The results demonstrate the β-amyloid conformation-dependent enhancement of cortical nitric oxide synthase (NOS) activity. Furthermore, chronic application of the polyamine site NMDA receptor blocker ifenprodil effectively attenuated β-amyloid neurotoxicity. We propose that n NOS activation reflects the degree of β-amyloid-induced excitotoxic injury in a proportional manner. Moreover, Ca 2+-mediated processes via NMDA receptors, or direct binding of β-amyloid to this receptor may be a critical step in the neurotoxic mechanisms in vivo.

Ethanol alone or with dexamethasone alters the kinetics of choline acetyltransferase

Choline acetyltransferase activity was measured in rats treated with daily injections of ethanol (0.1 g/kg body wt) and or dexamethasone (1 mg/kg body wt) for 5 consecutive days. Ethanol produced a biphasic reduction of choline acetyltransferase activity in rat cerebral cortex, which at most time points was further decreased by simultaneous injection of dexamethasone. Kinetic studies of cortex choline acetyltransferase activity in rats that had received 5 daily injections of ethanol or ethanol and dexamethasone indicated that the observed reduction in enzyme activity was due to an apparent reduction in affinity ( K m) of the enzyme for acetyl coenzyme A with no significant change in the total amount of enzyme present ( V max). This finding has implications with respect to the use of choline acetyltransferase as a marker for cholinergic neurons, and for the understanding of the regulation of choline acetyltransferase activity in the brain.

307. - Atropine selectively reduces metabolic activity in rat cerebral cortex

307. - Atropine selectively reduces metabolic activity in rat cerebral cortex