Altered somatosensory barrel cortex refinement in the developing brain of Mecp2-null mice.
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2) gene. In previous studies, monoaminergic dysfunctions have been detected in patients with RTT and in a murine model of RTT, the Mecp2-null mouse. Therefore, the pathogenesis of RTT is thought to involve impairments in the monoaminergic systems. However, there have been limited data showing that the impairment of monoamines leads to early symptoms during development. We used histochemistry to study the somatosensory barrel cortex in the B6.129P2(C)-Mecp2(tm1.1Bird) mouse model of RTT. The barrel cortex is widely used to investigate neuronal development and its regulation by various neurotransmitters including 5-HT. 5-HT levels were measured by high performance liquid chromatography with electrochemical detection (HPLC/EC), and serotonin transporter (SERT) and 5-HT1B receptor mRNAs were measured in the somatosensory cortex, thalamus and striatum on postnatal days (P) 10, P20 and P40. Mecp2-null mice (Mecp2-/y) had significantly smaller barrel fields than age-matched wild-type controls (Mecp2+/y) on P10 and P40, but the topographic map was accurately formed. Levels of 5-HT, and SERT and 5-HT1B receptor mRNA expression in the somatosensory cortex did not differ significantly between the Mecp2-null and wild-type mice on P10. However, thalamic 5-HT was reduced in Mecp2-null mice. Our data indicate that a lack of MeCP2 may disturb the refinement of the barrel cortex in the early postnatal period. Our findings suggest that a decrease in thalamic 5-HT might be involved in this phenomenon.
Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address: moroto@koto.kpu-m.ac.jp.
M
M
Moroto
A
A
Nishimura
M
M
Morimoto
K
K
Isoda
T
T
Morita
M
M
Yoshida
S
S
Morioka
T
T
Tozawa
T
T
Hasegawa
T
T
Chiyonobu
K
K
Yoshimoto
H
H
Hosoi
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000254:growth & development / Q000378:metabolism*
D051783:Methyl-CpG-Binding Protein 2; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin
5-HIAA; 5-HT; 5-hydroxyindoleacetic acid; ANOVA; Barrel cortex; CO; HPLC/EC; MAO; MeCP2; P; PBS; PMBSF; RIM; RTT; Rab3-interacting molecule; Rett syndrome; SD; SERT; Serotonin; Somatosensory; analysis of variance; cytochrome oxidase; high performance liquid chromatography with electrochemical detection; methyl-CpG binding protein 2; monoamine oxidase; phosphate-buffered saline; posteromedial barrel subfield; postnatal day; serotonin; serotonin transporter; standard deviation