Several Regions Of Rat Brain Research Articles

Effects on the Post-translational Modification of H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 Levels in Cerebral Cortex, Hypothalamus and Pons of Rats after a Systemic Administration of Cannabidiol: A Preliminary Study.

Cannabidiol (CBD), a non-psychotropic constituent of Cannabis sativa, has shown therapeutic promises by modulating several pathological conditions, including pain, epilepsy autism, among others. However, the molecular mechanism of action of CBD remains unknown and recent data suggest the engagement on CBD´s effects of nuclear elements, such as histone activity. This study assessed the changes in the post-translational modification (PTM) on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 in several brain regions of rats after the administration of CBD (20 mg/Kg/i.p.). To evaluate the effects on the PTM of histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 levels in the cerebral cortex, hypothalamus and pons of CBD-treated rats. Ten adult rats were randomly assigned into 2 groups: Control or CBD (20 mg/Kg/i.p). Animals were sacrificed after treatments and brains were collected for dissections of the cerebral cortex, hypothalamus and pons. Samples were analyzed for PTM on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 levels by Western blot procedure. CBD increased the PTM levels on the histones H3K4Me3, H3K9ac, and H3K27Me3 in the cerebral cortex whereas no significant differences were found in H3K9Me2 and H3K36Me2. In addition, in the hypothalamus, CBD decreased the contents of H3K9ac while no significant effects were observed in H3K4Me3, H3K9Me2, H3K27Me3, and H3K36Me2. Lastly, in the pons, CBD- treated rats showed a significant decline on the PTM levels of H3K4Me3 whereas no statistical differences were found in H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2. The study showed that CBD induced differential effects in levels of PTM on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 in several brain regions.

Increased Capacity and Density of Choline Transporters Situated in Synaptic Membranes of the Right Medial Prefrontal Cortex of Attentional Task-Performing Rats

Cholinergic neurons innervating the cortex have been conceptualized as a major component of the attention system of the brain. Because of recent evidence indicating plastic mechanisms regulating choline transporter (CHT)-mediated high-affinity choline uptake, which is the rate-limiting step of acetylcholine synthesis, the present experiment determined the capacity of cholinergic terminals to transport choline, and the proportion of choline transporters localized in the membrane of synaptic terminals, in several brain regions of rats performing a cognitive vigilance task (CVT) and a simple reaction time task (SRTT) and nonperforming (NP) rats. Compared with evidence from NP rats, increased choline transporter capacity [as indicated by maximum transporter velocity (Vmax)] and an increased density of CHTs situated in synaptic plasma membrane, relative to intracellular locations, were observed in the medial prefrontal cortex of the right but not left hemisphere of CVT-performing animals. Furthermore, right medial prefrontal Vmax values of CVT-performing rats correlated positively and left medial Vmax values correlated negatively with the animals' performance in signal trials. Measures of CHT function in the brains of SRTT-performing animals did not differ significantly from those in NP rats. The present data support the hypothesis that an increased capacity of choline transporters in the right medial prefrontal cortex, primarily attributable to increased trafficking of transporters from intracellular compartments to the terminal membrane, represents a cellular mechanism contributing to the mediation of attentional performance.

Age-related and regional differences in secretin and secretin receptor mRNA levels in the rat brain

In the present study expression levels of secretin and secretin receptor mRNAs in several brain regions of rats ranging in age from postnatal days 7 to 60 were investigated by quantitative real-time PCR. Expression of secretin and secretin receptor was detected in the central amygdala, hippocampus, area postrema, nucleus of the tractus solitary and cerebellum. The cerebellum expressed secretin receptor at significantly higher levels than that found in other brain regions within all the ages examined. In contrast, secretin mRNA was significantly higher in the nucleus of the tractus solitary than in the other four brain regions examined in postnatal day-21, -30 and -60 rats. Within most brain regions, both secretin and secretin receptor mRNAs were more abundant in postnatal day-7 and -14 rats as compared to postnatal day-21, -30 and -60 rats. Thus, secretin and its receptor are widely expressed in rat brain and the expression of both genes is developmentally regulated during the first few weeks following birth.

Effect of ischemia on TBARS and lactate production in several cerebral regions of anaesthetised and awake rats

The premise of neuroprotective therapy for acute ischemic stroke is based upon the possibility to interfere with the cellular ischemic cascade, so the understanding of the mechanisms and consequences of cerebral ischemia is necessary. The relationship between lipid peroxidation and acidosis was investigated in several regions of rat brain following ischemia without reperfusion. Male Wistar rats (280–300 g) were anaesthetised (Ketalar 33 mg/kg and Rompun 6.66 mg/kg) or not and underwent a four-vessel occlusion for 5 minutes. Then, thiobarbituric acid-reactive substances (TBARS) and lactate levels were measured in different brain regions (cerebellum, bulb, striatum, hippocampus, cortex). Induction of ischemia by ligation of two common carotid arteries and two vertebral arteries resulted in a production of TBARS (40–120%, p < 0.05) and lactate (20–60%, p < 0.05) in all cerebral regions of awake rats, especially in striatum, suggesting a potential link between lipid peroxidation and acidosis. When ischemia was realised on anaesthetised animals, an increase of lactate levels (30–50%, p < 0.05) was shown in all brain regions but TBARS were produced only in striatum (82%, p < 0.05). These data showed the particular vulnerability of striatum to ischemia and the possible opposite effects of an anaesthesia.

Dynamics of histamine H 3 receptor antagonists on brain histamine metabolism: do all histamine H 3 receptor antagonists act at a single site?

Thioperamide, the prototypical histamine H 3 receptor antagonist, acts at the brain histamine H 3 autoreceptor to promote the release and metabolism of neuronal histamine, resulting in higher brain levels of the metabolite tele-methylhistamine. However, unlike thioperamide, several new histamine H 3 receptor antagonists enter the central nervous system (CNS), block brain histamine H 3 receptors and increase histamine release without increasing brain tele-methylhistamine levels. Experiments were performed presently in an attempt to understand these results. Consistent with previous findings, thioperamide significantly increased the content and synthesis rate of tele-methylhistamine in mouse and rat brain. In contrast, the histamine H 3 receptor antagonists GT-2227 (4-(6-cyclohexylhex- cis-3-enyl)imidazole) and clobenpropit did not affect tele-methylhistamine synthesis rate in mouse whole brain. The histamine H 3 receptor ligand GT-2016 (5-cyclohexyl-1-(4-imidazol-4-ylpiperidyl)pentan-1-one) had no effect on tele-methylhistamine levels in any rat brain region and decreased tele-methylhistamine synthesis rates in the mouse whole brain. To examine the possibility that these histamine H 3 receptor antagonists might prevent the methylation of newly released histamine, they were co-administered with thioperamide to determine their effects on the thioperamide-induced stimulation of tele-methylhistamine synthesis. GT-2016 significantly reduced the thioperamide-induced activation of tele-methylhistamine synthesis in mouse whole brain and in several regions of rat brain. Although further clarification is needed, these results suggest that some histamine H 3 receptor antagonists may promote the release of neuronal histamine, but also act to reduce histamine methylation in vivo by an unknown mechanism.

Studies on the neuroprotective effect of the enantiomers of AR-A008055, a compound structurally related to clomethiazole, on MDMA ("ecstasy")-induced neurodegeneration in rat brain.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") administration produces neurotoxic degeneration of 5-HT nerve endings in several regions of rat brain. Administration of the GABAmimetic drug clomethiazole protects against this damage. We wished to see whether the enantiomers of AR-A008055 (1-4-methyl-5-thiazolyl-1-phenyl-methylamine), a compound structurally related to clomethiazole, were also neuroprotective against MDMA-induced degeneration. (R)-(+)-AR-A008055 or (S)-(-)-AR-A008055 (100 mg/kg IP) was injected 5 min prior to and 55 min after MDMA (15 mg/kg IP) administration to Dark Agouti rats. Rectal temperature was measured during this time and the concentration of 5-HT and 5-HIAA measured in hippocampus, cortex and striatum 7 days later. [3H]-Paroxetine binding was also measured in cortex. Both enantiomers abolished the acute MDMA-induced hyperthermia and attenuated the subsequent neurotoxic loss of 5-HT, 5-HIAA and [3H]-paroxetine binding. When rats given the enantiomer plus MDMA were warmed to keep their rectal temperature elevated to near that of animals given only MDMA, the neuroprotective effect of (S)-(-)-AR-A008055 was still seen, while the effect of (R)-(+)-AR-A008055 was abolished. Protection was also seen when (S)-(-)-AR-A008055 (50 mg/kg) was given, a dose which produced only a modest attenuation of MDMA-induced hyperthermia. The current data suggest that a major proportion of the neuroprotective action of (S)-(-)-AR-A008055 did not involve an attenuating effect on MDMA-induced hyperthermia. The protection afforded by (R)-(+)-AR-A008055, which is not a GABA agonist, appears to be solely due to its action on body temperature, strengthening the contention that abolishing the acute MDMA-induced hypothermia can produce neuroprotection. Since (S)-(-)-AR-A008055 has a similar pharmacology to clomethiazole, these data suggest that drugs which increase GABAA receptor channel opening are neuroprotective against MDMA-induced damage.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy)-induced egr-1 mRNA in rat brain: pharmacological manipulation

Using in situ hybridization and immunohistochemical techniques, we examined the expression pattern of egr-1 mRNA and Egr-1 protein in several brain regions following administration of 3,4-methylenedioxymethamphetamine (MDMA). Furthermore, we also studied the role of N-methyl- d-aspartate (NMDA) receptor, dopamine D 1 receptor, 5-hydroxytryptamine (5-HT) transporter or 5-HT 2A receptor in the induction of egr-1 mRNA by MDMA. Basal constitutive levels of egr-1 mRNA were detected in control rat brains. A single administration of MDMA (10 mg/kg) caused marked induction of egr-1 mRNA in the prefrontal cortex, striatum and hippocampal dentate gyrus. However, no changes in the egr-1 mRNA levels were detected in the CA1 region of hippocampus and occipital cortex after administration of MDMA (10 mg/kg). Furthermore, the expression of egr-1 mRNA in the prefrontal cortex, striatum and hippocampal dentate gyrus after administration of MDMA (10 mg/kg) was blocked significantly by pretreatment with NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]-cyclohepten-5,10-imine ((+)-MK801; 1 mg/kg), dopamine D 1 receptor antagonist SCH 23390 (1 mg/kg) or 5-HT uptake inhibitor paroxetine (5 mg/kg), but not by 5-HT 2A receptor antagonist SR46349B (5 mg/kg). However, high basal levels of Egr-1 immunoreactivity in the rat brain were not altered by administration of MDMA (10 mg/kg). These results suggest that MDMA alters the expression of egr-1 mRNA in several regions of rat brain, and that the expression of egr-1 mRNA by MDMA in the prefrontal cortex, striatum and hippocampal dentate gyrus appears to be mediated, at least in part, by NMDA receptor, dopamine D 1 receptor and 5-HT transporter.

Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats.

This study investigated the effects of chlorpheniramine (CPA, 10-25 mg/kg), diphenhydramine (DIPH, 20 mg/kg), tripelennamine (TRIP, 20 mg/kg), and pyrilamine (PYRI, 20 mg/kg) on 3, 4-methylenedioxymethamphetamine (MDMA, 20 mg/kg x 2)-induced hyperthermia and depletion of indoles in rat brains, on the uptake of serotonin and dopamine into rat synaptosomes, on the binding affinity of CPA for biogenic amine transporters in the synaptosomes of rat brain, and on the scavenging hydroxyl free radicals activity. Rats were treated with two injections of MDMA, CPA, DIPH, TRIP, PYRI, and saline, alone or in combination of MDMA with one of the antihistamines, 6 h apart and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injections for 13 h. As compared to saline controls, MDMA increased body temperature and decreased levels of indoles, measured by HPLC, in several brain regions of rats. CPA attenuated and DIPH had no effect on MDMA-induced hyperthermia, yet both attenuated the depletion of indoles, whereas PYRI and TRIP potentiated these effects. CPA inhibited the binding of [(3)H]paroxetine and [(3)H]nisoxetine to the synaptosomes of cerebral cortex and of [(3)H]win 35,428 to the synaptosomes of striatum. CPA, DIPH, TRIP, and PYRI inhibited [(3)H]serotonin uptake. CPA, PYRI, and TRIP, but not DIPH, scavenge hydroxyl radicals. Possible mechanisms of the different effects of the antihistamines on MDMA-induced hyperthermia and depletion of serotonin are discussed. Published 1999 Wiley-Liss, Inc.

Expression of Fos protein in rat brain following administration of a nicotinic acetylcholine receptor agonist epibatidine

Epibatidine (exo-2-(6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane), an extract of frog skin, is a novel and highly potent agonist for the nicotinic acetylcholine (ACh) receptor. The present study was undertaken to examine the expression of Fos protein in several rat brain regions following an acute administration of epibatidine. Furthermore, we also studied the role of the dopamine D 1 and D 2 receptors and the N-methyl- d-aspartate (NMDA) receptor, and nicotinic ACh receptor in the expression of Fos protein by epibatidine. A single administration of epibatidine (5, 10, 50 μg/kg) caused a marked induction of Fos-immunoreactivity in the prefrontal cortex, medial striatum, nucleus accumbens, amygdala and superior colliculus of rat brain. In these regions, pretreatment with SCH 23390 (1.0 mg/kg), a dopamine D 1 receptor antagonist, MK-801 (1.0 mg/kg), a NMDA receptor antagonist, and mecamylamine (5.0 mg/kg), a nicotinic Ach receptor antagonist, inhibited the induction of Fos protein by epibatidine (10 μg/kg). Pretreatment with sulpiride, a dopamine D 2 receptor antagonist, blocked the induction of Fos protein in the prefrontal cortex and the core region of accumbens nucleus, but not in the medial striatum and the shell division of nucleus accumbens of rat brain. These results suggest that epibatidine induced the expression of Fos protein in several regions of rat brain, and that dopamine D 1 receptor, NMDA receptor, and nicotinic ACh receptor may play a role in the expression of Fos protein by epibatidine in rat brain. Furthermore, dopamine D 2 receptor may, in part, play a role in epibatidine induced expression of Fos protein in the prefrontal cortex and the core region of nucleus accumbens, but not in the medial striatum and the shell division of nucleus accumbens of rat brain.

Induction of Fos protein by 3,4- methylenedioxymethamphetamine (Ecstasy) in rat brain: regional differences in pharmacological manipulation.

Psychostimulant drugs have been reported to increase the expression of some immediate-early genes in the brain. In the present study, immunohistochemical techniques were used to assess the pattern of Fos protein produced by 3,4-methylenedioxymethamphetamine (MDMA) in several brain regions. Furthermore, we also studied the role of the dopamine D and D receptors and the N-methyl- D-aspartate (NMDA) receptor in the induction of Fos protein by MDMA. A single administration of MDMA (5, 10 or 20 mg/kg) caused marked induction of Fos-immunoreactivity in several regions including frontal cortex, striatum and olfactory tubercle of rat brain, in a dose-dependent manner. However, in the hippocampus and cerebellum, there were few or no Fos immunoreactive cells induced by MDMA. Furthermore, the induction of Fos protein in the striatum and olfactory tubercle after administration of MDMA (10 mg/kg) was blocked by pre-treatment with the dopamine D receptor antagonist SCH 23390 (1 mg/kg) or the NMDA receptor antagonist dizocilpine (1 mg/kg), but not by the dopamine D receptor antagonist (-)-sulpiride (100 mg/kg). However, the induction of Fos protein in the frontal cortex and hippocampus by MDMA was unaltered by pretreatment with SCH 23390 (1 mg/kg) or (-)-sulpiride (100 mg/kg). These results suggest that MDMA induces the expression of Fos protein in several regions of rat brain, and that the expression of Fos protein by MDMA in the striatum and olfactory tubercle appears to be mediated at least in part by the dopamine D and NMDA receptors.

Chronic hypoxia induces modification of the N-methyl- d-aspartate receptor in rat brain

This study examined [ 3H]MK-801 binding to the N-methyl- d-aspartate (NMDA) receptor in membranes prepared from cerebral cortex, hippocampus and corpus striatum of 3 week old rats exposed to 10 weeks of intermittent hypobaric hypoxia (4300 m; 450 Torr) and compared results with those of normoxic controls. The cortex, hippocampus and striatum of hypoxic animals had a 36, 35 and 31% reduction in binding sites ( B max ) and a 29, 32 and 17% decrease (reflecting increased affinity) in the dissociation constant ( K d ) when compared to controls. In the cerebral cortex, both glutamate (100 μM) and glycine (10 μM) enhanced [ 3H]MK-801 binding by two to 3-fold. Coagonist glutamate, however, had a higher EC 50 (0.44 μM) in the hypoxic cortical membranes when compared to controls (0.28 μM). No significant differences were found in the EC 50 of glycine. The results show that the NMDA receptor is altered in several brain regions of rats developing in a hypoxic environment.

Detection of extended distribution of beta2-thyroid hormone receptor messenger ribonucleic acid (RNA) in adult rat brain using complementary RNA in situ hybridization histochemistry.

In situ hybridization histochemistry using a complementary RNA probe, directed at the entire length of the thyroid hormone receptor beta2 (TRbeta2)-specific region (-56 to 495 bp), was used to evaluate expression of TRbeta2 messenger RNA (mRNA) in coronal sections of adult rat brain. An extended distribution and intense expression of TRbeta2 mRNA was found in several regions of rat brain, including regions where TRbeta2 mRNA had not been previously identified using PCR or in situ hybridization histochemistry. These areas included hippocampus (dentate gyrus and C1, -2, and -3), cerebral cortex (predominantly layer 3), arcuate nucleus, median eminence, medial geniculate nucleus, tegmental bundle, medial and lateral lemniscus, Purkinje layer of the cerebellum, and several brain stem nuclei. In conclusion, we have developed a highly sensitive and specific method to demonstrate TRbeta2 mRNA expression in adult rat brain. The present findings are in agreement with immunoreactive TRbeta2 studies of rat brain and argue against the presence of an unidentified T3-binding protein to explain the previous discordant results of TRbeta2 mRNA and protein studies. In addition, the specificity of distribution of TR beta2 mRNA to certain brain nuclei, particularly those involved in hearing, implies a specific functional role of this receptor subtype and provides a physiological basis to understand the effects of hypothyroidism on brain development.

Valproate and its major metabolite E-2-en-valproate induce different effects on behaviour and brain monoamine metabolism in rats

The antiepileptic drug valproate has previously been shown to increase serotonin and dopamine turnover in certain brain regions, but the role of these alterations in the diverse pharmacodynamic effects of valproate is not known. For instance, monoamines have been implicated in the ‘wet dog’ shake behaviour induced by valproate in rats. E-2-en-valproate, a major metabolite of valproate, exhibits the same profile and potency of anticonvulsant activity as valproate, but does not induce wet dog shakes in rats. When administered at about equipotent anticonvulsant doses, both valproate and E-2-en-valproate increased serotonin metabolism in several brain regions of rats, although wet dog shakes were only seen after valproate, thus indicating that wet dog shake behaviour in response to valproate is not mediated by alterations in serotonin. Dopamine metabolism was differentially altered by the two compounds, with marked increases in 3,4-dihydroxyphenylacetic acid or homovanillic acid seen in frontal cortex and brainstem after valproate but not E-2-en-valproate, while the latter drug but not valproate significantly increased 3,4-dihydroxyphenylacetic acid in the amygdala. Levels of noradrenaline were not significantly altered in any of the 8 brain regions examined.

Ontogeny of NMDA R1 subunit protein expression in five regions of rat brain

A polyclonal antiserum to a fusion protien corresponding to a region of the NMDA R1 (NR1) subunit (amino acids 656–811) was produced and affinity purified. A quantitative immunoblotting technique was developed using the fusion protein as a standard. By employing this method, ontogenic studies (day 2–42) of the density of NR1 protein were carried out in several regions of rat brain. The results showed that in all five of the brain regions examined [olfactory bulb (Ob), cortex (Cx), hippocampus (Hp), midbrain (Mb) and cerebellum (Cb)], levels of NR1 protein are low at birth and increase with similar patterns having a sharp rise within the first 3 weeks after birth. Levels increased 2.0 to 4.5-fold from postnatal day 2 to postnatal day 42. Although the general patterns of developmental expression are similar, large differences in the absolute amounts of NR1 protein among the five brain regions were observed. The maximal levels (pmol of fusion protein equivalent/mg±S.E.) of NR1 subunit attained during development in the five regions are: Hp 2.0 ± 0.37 > Cx 1.4 ± 0.11 > Ob 1.3 ± 0.2 > Mb 1.0 ± 0.10 > Cb 0.57 ± 0.13. The temporal patterns of expression of NR1 protein are similar to results from studies examining the expression of NR1 mRNA. Furthermore, the absolute numbers obtained from our studies are close to those found using [ 3H]MK-801 binding suggesting that many of the NR1 subunits expressed in the brain exist in an active form.

Dopamine transporter immunohistochemistry in median eminence, amygdala, and other areas of the rat brain.

In an extension of our previous work, an antibody directed against a peptide from the N-terminal region of DAT was used to localize specific dopamine transporter immunoreactivity (DAT-IR) in several regions of rat brain. Apparent axons and varicosities were found in the zona incerta, external layer of the median eminence, various nuclei of the amygdala, the cortex-amygdala transition zone, and in periglomerular regions in the olfactory bulb. Apparent stained neuronal perikarya and dendrites were observed in the arcuate nucleus and olfactory bulb. These regions are known to have dopaminergic neurons and innervations, although there was not a perfect correspondence between DAT-IR and the known distribution of dopaminergic neurons. A possible explanation is that different dopamine containing cell groups express different levels of DAT mRNA and protein, as we have previously shown. Also in the tuberoinfundibular neurons, for example, DAT-IR was preferentially localized to distal axons in the median eminence, suggesting intracellular compartmentation.

The suppression of age-related accumulation of lipid peroxides in rat brain by administration of Rooibos tea ( Aspalathus linearis)

The protective effects of Rooibos tea (RT), Aspalathus linearis, against damage to the central nervous system (CNS) accompanying aging were examined by both the thiobarbituric acid reaction (TBA) and magnetic resonance imaging (MRI) methods in brains of chronically RT treated rats. Ad libitum administration of RT was begun with 3-month-old Wistar female rats and continued for 21 months. The contents of TBA reactive substances (TBARS) in the frontal cortex, occipital cortex, hippocampus and cerebellum in 24-month-old rats after administration with water were significantly higher than those in young rats (5 weeks old). However, no significant increase of TBARS was observed in RTadministered aged rats. When MR images of the brains of 24-month-old rats with and without RT as well as 5-week-old rats were taken, a decrease of the signal intensity was observed in the cerebral cortex, hippocampus and cerebellum in MR images of aged rats without RT, whereas little change of the signal intensity was observed in MR images of the same regions of 24-month-old rats treated with RT, whose images were similar to those of young rats. These observations suggested that (1) the age-related accumulation of lipid peroxides in the brain was closely related to the morphological changes observed by MRI, and (2) chronic RT administration prevented age-related accumulation of lipid peroxides in several regions of rat brain.

Developmental regulation of brain-derived neurotrophic factor messenger RNAs transcribed from different promoters in the rat brain

During the development of the nervous system many types of neurons are produced in excess and die because they fail to obtain sufficient amounts of target-derived neurotrophic factors (for review, see Refs 1, 16). Brain-derived neurotrophic factor is a protein that belongs to the nerve growth factor family of neurotrophins (for review, see Ref. 17) which promotes the survival and differentiation of distinct neuronal populations that partially overlap with those affected by the other members of the family (for review, see Ref. 11). We have recently shown that four promoters direct tissue specific expression of the rat brain-derived neurotrophic factor gene. In the present study we have quantified the levels of brain-derived neurotrophic factor messenger RNAs transcribed from different promoters during the rat brain development. Our data show that different promoters have specific regulation patterns during embryonic development but are regulated coordinately in several regions of rat brain during postnatal development, suggesting that the four transcription units have both distinct and common regulatory elements. Quantification of absolute levels of brain-derived neurotrophic factor messenger RNA revealed that it is expressed significantly higher in the rat brain than previously estimated.

Regional differences in the in vivo regulation of the extracellular levels of noradrenaline and its metabolites in rat brain

Microdialysis was used to determine extracellular levels of both noradrenaline and its metabolites in several brain regions of rats under basal conditions and in response to drugs selective for theα 2-adrenoceptor to study regional differences in the regulation of noradrenaline overflow. Basal overflow of noradrenaline was about 1.3 fmol/min in frontoparietal cortex, amygdala and hippocampus and in the medial prefrontal cortex 2.4 fmol/min was measured, whereas the overflow of the noradrenaline metabolites 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol was 10-fold higher. After correction for recovery and membrane length no regional differences in the basal overflow of noradrenaline (NA) were found. There were, however, regional differences in the drug-induced effects: locally applied moxonidine decreased extracellular noradrenaline stronger in the frontoparietal cortex than in the medial prefrontal cortex. The increase in noradrenaline overflow caused by idazoxan (10 −4M) was stronger in frontoparietal cortex than in amygdala and hippocampus. The metabolites were also generally decreased by moxonidine and increased by idazoxan, although less markedly. The present study shows that the regulation of noradrenaline overflow by the presynapticα 2-autoreceptor was stronger in cortical regions than in amygdala and hippocampus. In those latter regions the uptake mechanisms probably plays a relatively more important role in the regulation of noradrenaline overflow.

Basic fibroblast growth factor mRNA increases in specific brain regions following convulsive seizures

Basic fibroblast growth factor (bFGF) is a trophic factor synthesized in the central nervous system (CNS), where it is believed to play a role in neuronal maintenance and repair. Little is known about the regulation of this growth factor in the CNS. To determine whether the expression of the bFGF gene in the brain of adult animals changes in response to alterations of neuronal activity, we examined bFGF mRNA levels in several brain regions of rats experiencing focally-evoked convulsive seizures. Seizures were induced by microinjecting bicuculline unilaterally into an epileptogenic site within the deep prepiriform cortex, area tempestas (AT). By 5 h after initiation of brief limbic motor seizures from AT, there was a four fold increase in the levels of bFGF mRNA in the entorhinal cortex, hippocampus and olfactory bulb, but not in the caudate-putamen. The maximal expression of bFGF mRNA was reached by 10 h after seizure onset. In the same animals, the mRNA encoding nerve growth factor (NGF) was increased in entorhinal cortex and hippocampus, but not in the olfactory bulb. Our results demonstrate that neuronal activity can influence bFGF expression in an anatomically selective fashion and that acute changes in bFGF can occur in the uninjured mature brain. The increase in bFGF expression in response to excessive activation of specific neuronal circuitry may represent an adaptive response to protect against potential injury in those circuits.

The receptor antagonist MK-801 induces increases in dopamine and serotonin metabolism in several brain regions of rats

MK-801 (dizocilpine maleate), a non-competitive, N-methyl-D-aspartate receptor antagonist which induces a characteristic phencyclidine-like motor syndrome in rodents, was administered to rats after handling habituation to examine the effects of this drug on concentrations of monoamines and their metabolites in 14 brain regions. MK-801 increased dopamine and serotonin metabolism in several regions, the most marked effects being determined in frontal and piriform cortex, nucleus accumbens and striatum. The data indicate that not only effects on dopaminergic transmission but also on serotonergic transmission may be involved in the pharmacological actions of MK-801.