Biomedical subjects

Mohsin Md Syed

Publications and source records attributed to Mohsin Md Syed.

3 recordsLinked to original sources

PubMed2005

Staphylococcus aureus-derived peptidoglycan induces Cx43 expression and functional gap junction intercellular communication in microglia.

Gap junctions serve as intercellular conduits that allow the exchange of small molecular weight molecules (up to 1 kDa) including ions, metabolic precursors and second messengers. Microglia are capable of recognizing peptidoglycan (PGN) derived from the outer cell wall of Staphylococcus aureus, a prevalent CNS pathogen, and respond with the robust elaboration of numerous pro-inflammatory mediators. Based on recent reports demonstrating the ability of tumor necrosis factor-alpha and interferon-gamma to induce gap junction coupling in macrophages and microglia, it is possible that pro-inflammatory mediators released from PGN-activated microglia are capable of inducing microglial gap junction communication. In this study, we examined the effects of S. aureus-derived PGN on Cx43, the major connexin in microglial gap junction channels, and functional gap junction communication using single-cell microinjections of Lucifer yellow (LY). Exposure of primary mouse microglia to PGN led to a significant increase in Cx43 mRNA and protein expression. LY microinjection studies revealed that PGN-treated microglia were functionally coupled via gap junctions, the specificity of which was confirmed by the reversal of activation-induced dye coupling by the gap junction blocker 18-alpha-glycyrrhetinic acid. In contrast to PGN-activated microglia, unstimulated cells consistently failed to exhibit LY dye coupling. These results indicate that PGN stimulation can induce the formation of a functional microglial syncytium, suggesting that these cells may be capable of influencing neuro-inflammatory responses in the context of CNS bacterial infections through gap junction intercellular communication.

Animals↗

PubMed2004

Stage-dependent dynamics and modulation of spontaneous waves in the developing rabbit retina.

We report here a systematic investigation of the dynamics, regulation and distribution of spontaneous waves in the rabbit retina during the course of wave development prior to eye opening. Three major findings were obtained in this longitudinal study. (1) Spontaneous retinal waves underwent three developmental stages, each of which displayed distinct wave dynamics, pharmacology and mechanism of generation and regulation. Stage I waves emerged prior to synaptogenesis and appeared as frequent, fast propagating waves that did not form spatial boundaries between waves. These waves could be inhibited by blockers of gap junctions and adenosine receptors, but not by nicotinic antagonists. Stage I waves lasted about one day (around embryonic day 22) and then switched rapidly to stage II, resulting in slower and less frequent waves that could be blocked by nicotinic antagonists and had a characteristic postwave refractory period and spatial boundaries between adjacent waves. Immediately after the transition from stage I to stage II, the waves could be reverted back to stage I by blocking nicotinic receptors, indicating the presence of mutually compensatory mechanisms for wave generation. Stage III waves emerged around postnatal day 3-4 (P3-4), and they were mediated by glutamtergic and muscarinic interactions. With age, these waves became weaker, more localized and less frequent. Spontaneous waves were rarely detected after P7. (2) GABA strongly modulated the wave dynamics in a stage- and receptor type-dependent manner. At stage I, endogenous GABAB activation downregulated the waves. The GABAB modulation disappeared during stage II and was replaced by a strong GABA(A/C)-mediated inhibition at stage III. Blocking GABA(A/C) receptors not only dramatically enhanced spontaneous stage III waves, but also induced propagating waves in >P7 retinas that did not show spontaneous waves, indicating a role of GABA inhibition in the disappearance of spontaneous waves. (3) Spontaneous retinal waves were found in both the inner and outer retina at all three stages. The waves in the outer retina (ventricular zone) also showed stage-dependent pharmacology and dynamics. Together, the results revealed a multistaged developmental sequence and stage-dependent dynamics, pharmacology and regulation of spontaneous retinal waves in the mammalian retina. The presence of retinal waves during multiple developmental stages and in multiple retinal layers suggests that the waves are a general developmental phenomenon with diverse functions.

Aging↗

PubMed2003

Spontaneous waves in the ventricular zone of developing mammalian retina.

Spontaneous rhythmic waves in the developing mammalian retina are thought to propagate among differentiated neurons in the inner retina (IR) and play an important role in activity-dependent visual development. Here we report a new form of rhythmic Ca(2+) wave in the ventricular zone (VZ) of the developing rabbit retina. Ca(2+) imaging from two-photon optical sections near the ventricular surface of the whole-mount retina showed rhythmic Ca(2+) transients propagating laterally as waves. The VZ waves had a distinctively slow Ca(2+) dynamics (lasting approximately 20 s) but shared a similar frequency and propagation speed with the IR waves. Simultaneous Ca(2+) imaging in VZ and multi-electrode array recording in the ganglion cell layer (GCL) revealed close spatiotemporal correlation between spontaneous VZ and IR waves, suggesting a common source of initiation and/or regulation of the two waves. Pharmacological studies further showed that all drugs that blocked IR waves also blocked VZ waves. However, the muscarinic antagonist atropine selectively blocked VZ but not IR waves at this developmental stage, indicating that IR waves were not dependent on VZ waves, but VZ waves likely relied on the initiation of IR waves. Eliciting IR waves with puffs of nicotinic or non-N-methyl-d-aspartate agonists in GCL produced atropine-sensitive waves in the VZ, demonstrating a unique, retrograde signaling pathway from IR to VZ. Thus differentiated neurons in the IR use spontaneous, rhythmic waves to send both forward signals to the central visual targets and retrograde messages to the developing cells in the VZ.

Animals↗