Serotoninergic modulation of mesolimbic and frontal cortical dopamine neurons

Potentiation of the effect of haloperidol on dopamine metabolism by the 5-HT uptake inhibitor CGP 6085 A, and antagonism of this effect by the 5-HT antagonist mianserin were observed in the mesolimbic area and the frontal cortex of the rat brain. A similar effect was reported earlier in the corpus striatum. This suggests that serotoninergic modulation of dopamine neurons is a generally-occurring phenomenon in the brain.     

Absence of dopamine sensitive adenylate cyclase in the A10 region, the origin of mesolimbic dopamine neurones.

Dopamine (DA) failed to stimulate the adenylate cyclase of the mesolimbic A10 DA nerve cell body area, in contrast to tis activating effect in the nigrostriatal A9 DA cell body area. The enzyme was stimulated by GMPPNP (a GTP analog) and NaF. This indicates the absence in the A 10 cell area of DA receptors with functional coupling on adenylate cyclase, in contrast to the A9 cell area where such DA receptors are believed to be located on afferent axon terminals.     

Number of dopamine neurons predicts prolactin levels in two inbred mouse strains

Mice of the BALB/cJ strain have more dopamine neurons than mice of the CBA/J strain. We now report that BALB/cJ mice have less circulating and pituitary prolactin than CBA/J mice, a relationship expected from the difference in tuberoinfundibular dopamine neuron number.     

Differential effects of the serotonin receptors on cultured rat cerebral cortical neurons

Effects of serotonin (5-HT) on cerebral cortical neurons were examined by patch clamp techniques. 5-HT produced a variety of responses such as outward (19/73 patches/neurons), slow inward (15/73 patches/neurons), fast inward (8/73 patches/neurons), and mixed currents (initially fast inward deflection followed by an outward response: 2/73 patches/neurons), with a latency of 12 sec, 15 sec, 0 sec, and 0 sec respectively, at a holding potential of −60 mV in whole-cell patches. The fast inward currents were again evoked by a selective 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (CPBG). In the cell-attached patch clamp configuration, 5-HT inside the patch pipette elicited single channel currents with slope conductances of 42 pS and 132 pS (4/42 patches/neurons). CPBG inside the patch pipette evoked inward single channel currents with a lower slope conductance of 41 pS (3/23 patches/neurons). In contrast, application of 5-HT or a 5-HT₂ receptor agonist, α-methyl-5-hydroxytryptamine-maleate, outside the patch pipette induced outward single channel currents with a major slope conductance of 140 pS (8/30 patches/neurons) or 135 pS (6/20 patches/neurons), respectively. These results indicate that the outward and fast inward currents may be mediated respectively by the 5-HT₂ receptor, which is coupled to a G-protein, and by the 5-HT₃ receptor, which contains the non-selective cation channel, and that the mixed type may be caused by both the 5-HT₂ and 5-HT₃ receptors. Received 27 September 1996; received after revision 4 November 1996; accepted 7 November 1996     

Number of dopamine neurons predicts prolactin levels in two inbred mouse strains

Summary Mice of the BALB/cJ strain have more dopamine neurons than mice of the CBA/J strain. We now report that BALB/cJ mice have less circulating and pituitary prolactin than CBA/J mice, a relationship expected from the difference in tuberoinfundibular dopamine neuron number.     

Neurotrophic effects of conditioned media of astrocytes isolated from different brain regions on hippocampal and cortical neurons

The present study was designed to reveal whether astroglial cells from different brain regions produce diffusible factors that differentially support the survival of neurons and the establishment of neuronal morphology. For this purpose, astrocyte conditioned media (ACM) were prepared by conditioning chemically-defined medium with type I astrocyte culture dissociated from cerebral cortex, hippocampus and hypothalamus. Hippocampal and cortical neurons were cultured in ACM or in non-conditioned medium. ACM derived from three brain regions all supported the survival of hippocampal and cortical neurons better than non-conditioned control medium. Of these, hypothalamic ACM was the most effective in supporting the survival of cortical neurons. The ACM also potentiated the elongation of the longest neurite of hippocampal and cortical neurons. However, there were no significant differences in the promoting effects on neurite elongation among ACM from three brain regions.     

Autophagic activity in cortical neurons under acute oxidative stress directly contributes to cell death

Primary neurons undergo insult-dependent programmed cell death. We examined autophagy as a process contributing to cell death in cortical neurons after treatment with either hydrogen peroxide (H₂O₂) or staurosporine. Although caspase-9 activation and cleavage of procaspase-3 were significant following staurosporine treatment, neither was observed following H₂O₂ treatment, indicating a non-apoptotic death. Autophagic activity increased rapidly with H₂O₂, but slowly with staurosporine, as quantified by processing of endogenous LC3. Autophagic induction by both stressors increased the abundance of fluorescent puncta formed by GFP-LC3, which could be blocked by 3-methyladenine. Significantly, such inhibition of autophagy blocked cell death induced by H₂O₂ but not staurosporine. Suppression of Atg7 inhibited cell death by H₂O₂, but not staurosporine, whereas suppression of Beclin 1 prevented cell death by both treatments, suggesting it has a complex role regulating both apoptosis and autophagy. We conclude that autophagic mechanisms are activated in an insult-dependent manner and that H₂O₂ induces autophagic cell death.     

Spread of cobalt from a cortical epileptic lesion induced by a cobalt-gelatine implant into the frontal cortex of the rat

Summary The spread of cobalt ions from cobalt induced epileptic foci in rats has been investigated. Atomic absorption spectrophotometry and heavy-metal histochemistry reveal cobalt ions spread very widely from the focus. Biochemical and physiological consequences for this model of epilepsy are discussed.     

Spread of cobalt from a cortical epileptic lesion induced by a cobalt-gelatine implant into the frontal cortes of the rat.

The spread of cobalt ions from cobalt induced epileptic foci in rats has been investigated. Atomic absorption spectrophotometry and heavy-metal histochemistry reveal cobalt ions spread very widely from the focus. Biochemical and physiological consequences for this model of epilepsy are discussed.     

Effect of large mesencephalic-diencephalic lesions on the noradrenalin,dopamine and 5-hydroxytryptamine neurons of the central nervous system

Zusammenfassung Nach Ausführung von grossen symmetrischen mesencephalisch-dicncephalischen Läsionen in Ratten konnte mit Hilfe von biochemischen und histochemischen Methoden eindeutig festgestellt werden, dass die Dopamin (DA), Noradrenalin (NA) und 5-Hydroxytryptamin (5-HT) enthaltenden Nerventerminalen im Prosencephalon zu grossen aufsteigenden DA, NA und 5-HT Neuronsystemen gehören. Die Zellkörper dieser Neuronensysteme sind im Gehirnstamm lokalisiert. Dies deutet darauf hin, dass ein einzelnes NA Neuron Gebiete innervieren kann, die weit auseinander liegen, zum Beispiel auf der einen Seite im Cerebellum, auf der anderen im Prosencephalon.     

Long-term depressor effects of noradrenaline and dopamine neurons transplanted into the third ventricle of the brain of salt-loaded hypertensive rats

Neural tissues including A 6 group noradrenaline neurons in the locus ceruleus or A 10 group dopamine neurons in the substantia nigra were transplanted into the third ventricle at the preoptic-anterior hypothalamic level of rats made hypertensive by salt loading. Either transplant exerted a long-lasting depressor effect.     

Long-term depressor effects of noradrenaline and dopamine neurons transplanted into the third ventricle of the brain of salt-loaded hypertensive rats

Summary Neural tissues including A 6 group noradrenaline neurons in the locus ceruleus or A 10 group dopamine neurons in the substantia nigra were transplanted into the third ventricle at the preoptic-anterior hypothalamic level of rats made hypertensive by salt loading. Either transplant exerted a long-lasting depressor effect.     

Lactacystin-induced apoptosis of cultured mouse cortical neurons is associated with accumulation of PTEN in the detergent-resistant membrane fraction

The tumor suppressor function of PTEN is attributed to its phospholipid phosphatase activity that dephosphorylates the plasma membrane phosphatidylinositol-(3,4,5)-triphosphate [PtdIns(3,4,5)P₃]. Implicit in this notion is that PTEN needs to be targeted to the plasma membrane to dephosphorylate PtdIns(3,4,5)P₃. However, the recruitment of PTEN to the plasma membrane is not fully understood. Here, we demonstrate PTEN accumulation in the detergent-insoluble fraction of neuronal cells in response to treatment by the proteasome inhibitor lactacystin. First, lactacystin induces apoptosis and the activation of caspase-3 in cultured cortical neurons. Second, PTEN undergoes proteolysis to form a truncated 50-kDa form that lacks parts of its C-terminal tail. Third, the truncated PTEN is stably associated with the detergent-insoluble fraction in which the plasma membrane marker protein flotillin-1 resides. Taken together, our results suggest that truncation and accumulation of PTEN to the detergent-insoluble membrane fraction are two events associated with the apoptotic signals of the proteasome inhibitor in cortical neurons.Received 24 March 2004; received after revision 26 May 2004; accepted 5 June 2004