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Effect of serotonin inhibition on glucocorticoid and mineralocorticoid expression in various brain structures.

Many studies have shown the existence of functional interactions between central neurotransmitter systems and the hypothalamo-pituitary adrenal axis. Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are regulated by multiple factors including glucocorticoids themselves. Neurotransmitters such as serotonin (5-hydroxytryptamine: 5-HT) can regulate brain corticosteroid receptors in a complex way. The present study examined the short-term (48 h) effects of parachlorophenylalanine (PCPA), a drug which specifically inhibits 5-HT synthesis, on corticosteroid receptor levels and on the expression of their respective messenger ribonucleic acids (mRNA) in the rat hippocampus, hypothalamus and brain stem. The study was performed in bilaterally adrenalectomized animals, in order to avoid potential drug-induced changes in plasma corticosterone levels, which could secondarily regulate MR and GR. Short-term inhibition of 5-HT synthesis by PCPA significantly increased the number of hippocampal MR-binding sites. PCPA treatment did not alter the number of GR-binding sites in the hippocampus, hypothalamus and brain stem. We observed no change in the affinities of GR and MR sites in all the structures studied. In PCPA-treated rats, restoration of control 5-HT levels by injection of its immediate precursor, 5-hydroxytryptophan (5-HTP) brings the number of hippocampal MR-binding sites back to control levels. It can therefore be concluded that the increase in number of MR-binding sites induced by acute PCPA treatment is dependent on the decrease in 5-HT levels. The increase in hippocampal MR binding sites was correlated with an induction of their messengers, suggesting that 5-HT modulates the synthesis of MR protein. Although PCPA did not modify the number of hippocampal GR-binding sites, a decrease in hippocampal GR mRNA expression was observed. This study shows that 5-HT inhibits hippocampal mineralocorticoid receptor synthesis and that this effect is not mediated by changes in corticosterone hormone secretion, and illustrates the existence of complex mechanisms for corticosteroid receptor regulation in the hippocampus.

5-Hydroxytryptophan↗

Brain structure in preclinical Huntington's disease.

BACKGROUND: Huntington's disease (HD) is traditionally conceptualized as a degenerative disease of the striatum. Recent scientific advances, however, have suggested neurodevelopmental contributions and extrastriatal brain abnormalities. This study was designed to assess the morphology of the brain in participants who had previously undergone elective DNA analyses for the HD mutation who did not currently have a clinical diagnosis of HD (preclinical HD subjects). METHODS: Twenty-four preclinical participants with the gene expansion for HD underwent brain magnetic resonance imaging and were compared with a group of 24 healthy control subjects, matched by gender and age. RESULTS: Huntington's disease preclinical participants had substantial morphologic differences from controls throughout the cerebrum. Volume of the cerebral cortex was significantly increased in preclinical HD, whereas the basal ganglia and cerebral white matter volume were substantially decreased. CONCLUSIONS: In individuals with the HD gene mutation who are considered healthy (preclinical for manifest disease), the morphology of the brain is substantially altered compared with matched control subjects. Although decreased volumes of the striatum and cerebral white matter could represent early degenerative changes, the novel finding of enlarged cortex suggests that developmental pathology occurs in HD.

Adult↗

Human brain structural change related to acute single exposure to sarin.

OBJECTIVE: This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin. METHODS: Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated. RESULTS: The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05). INTERPRETATION: Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

Adult↗

Brain structures related to active and passive finger movements in man.

A PET study was performed in six normal volunteers to elucidate the functional localization of the sensory afferent component during finger movement. Brain activation during the passive movement driven by a servo-motor was compared with that during an auditory-cued active movement which was controlled kinematically in the same way as the passive one. A newly developed device was used for selectively activating proprioception with a minimal contribution from tactile senses. Active movement was associated with activation of multiple areas, including the contralateral primary sensorimotor cortex, premotor cortex, supplementary motor area (SMA), bilateral secondary somatosensory areas and basal ganglia and ipsilateral cerebellum. In contrast, only the contralateral primary and secondary somatosensory areas were activated by the passive movement. It is likely that the contribution of proprioceptive input to the activation of the premotor cortex, SMA, cerebellum and basal ganglia, if any, is small. However, the present results do not rule out the possibility that the cutaneous afferent input or the combination of cutaneous and proprioceptive input participates in the activation of those areas during the active movement.

Acoustic Stimulation↗

[Luminescent-histochemical study of the effect of atropine and dimethoxydichlorvinylphosphate on catecholamine concentration in certain rat brain structures].

Histofluorescence was used to study the effect of atropine (5 mg/kg) and dimethoxychlorvinylphosphate (DDVP, 10 mg/kg) on the content of noradrenaline (NA) and dopamine (DA) in some regions of the rat brain. The animals were sacrificed 30 minutes after administration of the drugs. It has been discovered that both atropine and DDVP increase the content of DA in the caudate nucleus and adjacent nuclei. In the NA-ergic system atropine reduces while DDVP increases the content of NA in the neurons of locus coeruleus. Interaction between the cholinergic and catecholaminergic neurotransmitter systems of the brain is discussed.

Animals↗