Molecular and cellular neurosciences
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Mol. Cell. Neurosci. · Apr 2003
Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis.
Rett syndrome, a neurodevelopmental disorder hypothesized to be due to defective neuronal maturation, is a result of mutations in the mecp2 gene encoding the transcriptional repressor methyl-CpG binding protein (MeCP2). We utilized the olfactory system, which displays postnatal neurogenesis, as a model to investigate MeCP2 expression during development and after injury. MeCP2 expression increased postnatally, localizing to mature olfactory receptor neurons (ORNs) and sustentacular supporting cells. ⋯ MeCP2 expression in the ORNs reached prelesioning levels as cells matured after ablation, whereas expression was not completely restored after bulbectomy, in which functional synaptogenesis cannot occur. Thus, MeCP2 expression correlates with the maturational state of ORNs, and precedes synaptogenesis. Identifying the time window of MeCP2 expression should help further clarify the biological defects in Rett syndrome.
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Mol. Cell. Neurosci. · Apr 2002
Opposing functions of GDNF and NGF in the development of cholinergic and noradrenergic sympathetic neurons.
We identified a population of mature sympathetic neurons in which Ret, the receptor for glial cell line-derived neurotrophic factor (GDNF), is coexpressed with the neurotrophin-3 (NT3) receptor TrkC and choline acetyltransferase. In a complementary population the nerve growth factor receptor TrkA is coexpressed with the norepinephrine transporter. ⋯ Signal transducer and activator of transcription-3 (STAT3) was strongly activated by CNTF but not by GDNF or NT3 and hence is not essential for cholinergic differentiation. We conclude that cholinergic properties can be regulated by neurotrophic factors from three different protein families, whereas noradrenergic properties are promoted by NGF.
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Mol. Cell. Neurosci. · Aug 2001
Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel.
Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal horn. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for alpha(1B,) the pore-forming subunit of the N-type calcium channel. ⋯ In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in alpha(1B) knockout mice. These results suggest that the alpha(1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.
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Mol. Cell. Neurosci. · Jan 1997
Regulation of expression of the sensory neuron-specific sodium channel SNS in inflammatory and neuropathic pain.
Increased voltage-gated sodium channel activity may contribute to the hyperexcitability of sensory neurons in inflammatory and neuropathic pain states. We examined the levels of the transcript encoding the tetrodotoxin-resistant sodium channel SNS in dorsal root ganglion neurons in a range of inflammatory and neuropathic pain models in the rat. Local Freund's adjuvant or systemic nerve growth factor-induced inflammation did not substantially alter the total levels of SNS mRNA. ⋯ SNS expression is thus little dependent on NGF even though SNS transcript levels dropped by more than 60% 7-14 days after axotomy. In the streptozotocin diabetic rat SNS levels fell 25%, while in several manipulations of the L5/6 tight nerve ligation rat neuropathic pain model, SNS levels fell 40-80% in rat strains that are either susceptible or relatively resistant to the development of allodynia. Increased expression of SNS mRNA is thus unlikely to underlie sensory neuron hyperexcitability associated with inflammation, while lowered SNS transcript levels are associated with peripheral nerve damage.
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Mol. Cell. Neurosci. · Oct 1994
The role of the hippocampal mineralocorticoid and glucocorticoid receptors in the hypothalamo-pituitary-adrenal axis of the aged Fisher rat.
The aging process has been frequently associated with hippocampal neurodegeneration, loss of corticosteroid receptors, and, at the same time, dysfunction of the hypothalamo-pituitary-adrenal (HPA) axis. We were interested in characterizing simultaneously the activity of the HPA axis and status of both corticosteroid receptors (mineralocorticoid or MR and glucocorticoid or GR) in the hippocampus of aged male Fisher-344 rats. We compared intact, adrenalectomized (ADX), and corticosterone-replaced ADX young (5-6 months) and old (26-27 months) rats, examining all the parameters in the same animals. ⋯ The fact that corticosterone was able to modulate the biosynthetic rate of MR and GR strongly suggests that the decrease of receptors is functional and not simply due to cell death in the aged hippocampus. We propose that in the aged Fisher rat the loss of hippocampal corticosteroid receptors is previous to any change in the circadian rhythm of circulating corticosterone. Furthermore, the altered turn-off of the corticosterone stress response observed in the same animals may be related to the reduction of functional MR and GR but it is not due to high basal levels of corticosterone.