Disease relevance of Mesencephalon

• Parkinson's disease is characterized by the loss of midbrain dopamine neurons that innervate the caudate and the putamen [1].
• Otx1-/- mice showed spontaneous epileptic behaviour and multiple abnormalities affecting mainly the telencephalic temporal and perirhinal areas, the hippocampus, the mesencephalon and the cerebellum, as well as the acoustic and visual sense organs [2].
• Microinfusions of rat prolactin into the dorsal midbrain of estrogen-treated, ovariectomized rats increased lordosis behavior [3].
• Selective blockade of hypothalamic hyperphagia and obesity in rats by serotonin-depleting midbrain lesions [4].
• Upregulation of ICAM-1 expression in the region of the midbrain correlates with increased retention of malaria-infected erythrocytes and with the symptoms of cerebral malaria [5].

Psychiatry related information on Mesencephalon

• INTERPRETATION: This result constitutes strong and direct evidence supporting Devinsky's hypothesis (Devinsky O. Neuroanatomy of Gilles de la Tourette's syndrome. Possible midbrain involvement. Arch Neurol 1983;40:508-514) according to which midbrain disturbances play an important pathogenic role in TS [6].
• Lesions included right cerebellar hypoplasia (bipolar disorder), bilateral cerebellar atrophy (rapid cycling unipolar mania and dystonia), and left midbrain pathology (mixed bipolar disorder, dystonia, and compulsion) [7].
• The roles of midbrain and diencephalic dopamine cell groups in the regulation of cataplexy in narcoleptic Dobermans [8].
• Immunocytochemical quantification of tyrosine hydroxylase at a cellular level in the mesencephalon of control subjects and patients with Parkinson's and Alzheimer's disease [9].
• CNS precursors derived from E12 rat mesencephalon proliferate in the presence of basic fibroblast growth factor and differentiate in vitro into functional dopaminergic neurons, which upon transplantation alleviate behavioral symptoms in a rat model of Parkinson's disease [10].

High impact information on Mesencephalon

• Identification of intrinsic determinants of midbrain dopamine neurons [11].
• These findings confirm the hypothesis that CFEOM2 results from the abnormal development of nIII/nIV (ref. 7) and emphasize a critical role for ARIX in the development of these midbrain motor nuclei [12].
• We also show that, consistent with results obtained using other methods, uncaging eng2a (which encodes the transcription factor Engrailed2a) in the head region during early development causes a severe reduction in the size of the eye and enhanced development of the midbrain and the midbrain-hindbrain boundary at the expense of the forebrain [13].
• Pax5 has an important role in B-cell and midbrain development [14].
• Analysis of embryos carrying different combinations of these alleles revealed requirements for Fgf8 gene function during gastrulation, as well as cardiac, craniofacial, forebrain, midbrain and cerebellar development [15].

Chemical compound and disease context of Mesencephalon

• Parkin gene mutations have been implicated in autosomal-recessive early-onset parkinsonism and lead to specific degeneration of dopaminergic neurons in midbrain [16].
• The widespread neuronal and glial localization of glutamate receptor subunits suggests that excitatory amino acids may act at different levels to control the basal activity and, possibly, to participate in the degeneration of midbrain dopaminergic neurons in Parkinson's disease [17].
• Glial cell line-derived neurotrophic factor (GDNF) injected intranigrally protects midbrain dopamine neurons against 6-hydroxydopamine (6-OHDA) toxicity [18].
• Three patients with progressive supranuclear palsy demonstrated atrophy of the midbrain, pons, cerebellum, and cerebral hemispheres by computed tomography with horizontal, sagittal, and coronal reconstruction [19].
• While there was no significant change in monoamine levels in brain regions after 2 hr, norepinephrine concentration in hypothalamus and midbrain decreased significantly after 13 hr of hypoxia [20].

Biological context of Mesencephalon

• These data define a key role for Pax5 in early B lymphopoiesis and midbrain patterning [21].
• Morphogenesis of the posterior midbrain was affected as early as embryonic day 16.5, leading to a reduction of the inferior colliculus near the midline and to altered foliation of the anterior cerebellum [21].
• Each signal is essential for embryonic development, Wnt-1 for midbrain patterning, and Wnt-3a for formation of the paraxial mesoderm, but the absence of a dorsal neural-tube phenotype in each mutant suggests that Wnt signalling may be redundant [22].
• The homeobox gene Otx2 is expressed in the anterior neural tube with a sharp limit at the midbrain/hindbrain junction (the isthmic organizer) [23].
• Here we use viral-mediated RNA interference (RNAi) to generate a specific knockdown of Th, the gene encoding the dopamine synthesis enzyme tyrosine hydroxylase, within midbrain neurons of adult mice [24].

Anatomical context of Mesencephalon

• Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain [25].
• These findings show that the caudal limit of Otx2 expression is sufficient for positioning the isthmic organizer and encoding caudal midbrain fate within the mid/hindbrain domain [23].
• Midbrain development induced by FGF8 in the chick embryo [26].
• During embryogenesis, the BSAP gene is transiently expressed in the mesencephalon and spinal cord with a spatial and temporal expression pattern that is distinct from that of other Pax genes in the developing central nervous system (CNS) [27].
• At clinically relevant doses, selective serotonin (5-HT) reuptake inhibitors (SSRIs) and MAO inhibitors (MAOIs) increase the extracellular concentration of 5-HT in the midbrain raphé nuclei, thereby activating inhibitory somatodendritic 5-HT1A autoreceptors [28].

Associations of Mesencephalon with chemical compounds

• In the midbrain, however, D1 receptors are selectively localized to the terminals of GABA (gamma-aminobutyric acid)-containing afferents [29].
• In ventral midbrain dopamine neurons, activation of metabotropic glutamate receptors (mGluR1) mobilized calcium from caffeine/ryanodine-sensitive stores and increased an apamin-sensitive potassium conductance [30].
• Nicotine activates and desensitizes midbrain dopamine neurons [31].
• Midbrain dopamine neurons normally help to shape behaviour by reinforcing biologically rewarding events, but addictive drugs such as cocaine can inappropriately exert a reinforcing influence by acting upon the mesolimbic dopamine system [31].
• Androgen-sensitive midbrain sites and visual attention in chicks [32].

Gene context of Mesencephalon

• By examining embryonic expression of the mouse engrailed (En) genes, from 8.0 to 9.5 days postcoitum, we demonstrate that Wnt-1 primarily regulates midbrain development [33].
• In rodents, glial-cell-line-derived neurotrophic factor (GDNF) stimulates an increase in midbrain dopamine levels, protects dopamine neurons from some neurotoxins, and maintains injured dopamine neurons [34].
• Here we report that expression of En-1 in the developing midbrain of Wnt-1-null embryos is sufficient to rescue early midbrain and anterior hindbrain development [35].
• The highly related members of the Brn-3 family have similar DNA-binding preferences and overlapping expression patterns in the sensory nervous system, midbrain and hindbrain, suggesting functional redundancy [36].
• Injection of Six3 RNA into medaka fish embryos causes ectopic Pax6 and Rx2 expression in midbrain and cerebellum, resulting in the formation of ectopic retinal primordia [37].

Analytical, diagnostic and therapeutic context of Mesencephalon

• The developmental potential of neural progenitors derived from the E13.5-E14 lateral or medial ganglionic eminences (LGE and MGE, respectively) or the E12 ventral mesencephalon (VM) was examined in cross-species transplantation model [38].
• Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 2 mRNA, but not GDNF mRNA, is expressed in the E14 rat midbrain floor and in mesencephalic cultures [39].
• Levels of DAT messenger RNA were quantified in the medial and lateral midbrain regions using in situ hybridization, and striatal DAT binding sites were assessed by quantitative autoradiography using the DAT-specific radioligand [3H]WIN 35428 [40].
• By combining in vivo electroporation with organotypic cultures, we show that an already identified BPAG1 enhancer/promoter is differentially regulated by homeoproteins Hoxc-8 and Engrailed in the embryonic spinal cord and mesencephalon [41].
• Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures [42].

References