Carman, A.J. et al. (2011) J. Neurosci. 31, 13272.
The permeability of the blood brain barrier (BBB) is critical for the uptake of drugs used for the treatment of neurological disorders such as Alzheimer's, Parkinson's and multiple sclerosis just to name a few. A study showed that activation of adenosine receptors, members of the G-protein coupled receptor (GPCR) superfamily increases the permeability of the BBB to a number of molecules. In addition, immunohistochemistry of mouse brain using Anti-Adenosine A1 Receptor Antibody (#AAR-006) and Anti-Adenosine A2A Receptor Antibody (#AAR-002) shows colocalization of these two receptors with CD31, a marker of brain endothelial cells, the major cellular constituent of the BBB. Furthermore, western blot analysis of primary brain endothelial cells from mice using the above mentioned antibodies, shows expression of both adenosine A1 and A2A receptors in these cells. In all, the exciting results in this study are an important part of the missing puzzle regarding drug delivery past the BBB.
Li, K.X. et al. (2011) Nat. Neurosci. 15, 267.
Defective fast-spiking interneurons is implicated in epilepsy. These neurons highly express ErbB4 receptor which is activated upon Neuregulin 1 (NRG1) binding. A study aimed at investigating the possible link between NRG1-ErbB4 signaling and epilepsy found that the ligand-receptor duo increases the excitability of neurons affected in epileptic seizures, by decreasing the voltage threshold via KV1.1 K+ channel. Treating cells with Alomone Labs Dendrotoxin-K (#D-400), KV1.1 channel blocker, also decreased the threshold current for the generation of action potentials. Overall, this study identifies the NRG1-ErbB4 system as a new possible target for the treatment of epilepsy.
Zhu, H. et al. (2011) J. Neurosci. 31, 15269.
The inositol 1,4,5-triphisphate (IP3) receptor (IP3R) is one of numerous receptors mediating Ca2+ release from intracellular stores. IP3 receptor-1 is closely localized to acetylcholine receptors and in postsynaptic areas surrounding neuromuscular junctions (NMJ) suggesting an important role for the receptor in those areas. Indeed, IP3R-1 was shown to be involved in mediating cholinergic signals at the NMJ. Furthermore, blocking the activity or knocking down IP3R-1 (demonstrated in immunocytochemistry and western blot analysis of C2C12 mouse myoblast cell line using Alomone Labs Anti-IP3 Receptor-1 Antibody (#ACC-019)) reversed the excitotoxic effects of cholinergic and synaptic Ca2+ overload, without affecting normal NMJ function. These observations suggest that inhibiting IP3R-1 may be a means to control conditions with excessive Ca2+ release.
Baruscotti, M. et al. (2011) Proc. Natl. Acad. Sci. U.S.A. 108, 1705.
HCN4 is a hyperpolarization-activated, cyclic nucleotide (HCN) channel making up 80% of the HCN channels expressed in the sinoatrial node, in the heart, and is responsible for the "funny" or pacemaker current. A tedious study in which inducible and cardiac specific HCN4 knockout mice were generated, showed that HCN4 channel is necessary for the generation and conduction of normal rhythm. In addition, the animals develop severe bradycardia and heart block, from which they eventually die. Immunohistochemical staining and western blot analysis of sinoatrial node tissue and cells using Alomone Labs Anti-HCN4 Antibody (#APC-052) show reduced expression of the channel in knockout animals.
Fulton S. et al. (2011) J. Biol. Chem. 286, 9360.
Alomone Labs α-Dendrotoxin (#D-350), Dendrotoxin-κ (#D-400), Maurotoxin (STM-340) and OsK-1 (RTO-150) were used as selective KV1.2 channel blockers establishing the involvement of K+ channels in the regulation process of axonal Dopamine release by axonal Dopamine 2 autoreceptor.
Mizoguchi H. et al. (2011) J. Neurosci. 31, 12963.
Alomone Labs Recombinant mouse proBDNF protein (#B-240) was injected into the hippocampal dentate gyrus and significantly enhanced kindling seizures in wild-type mice versus Matrix Metalloproteinase 9 (MMP-9) knockout mice. These findings suggest that MMP-9 is involved in the progression of behavioral phenotypes in kindled mice as a result of the conversion of pro-BDNF to mature BDNF in the hippocampus.
Tanner, G.R. et al. (2011) J. Neurosci. 31, 8689.
Alomone Labs Charybdotoxin (#RTC-325*) was used as a non-KATP blocker in perforated-patch recording, in order to show that KATP channels contribute to the slow after-hyperpolarization following an evoked burst of action potentials. Activity-dependent opening of KATP channels help granule cells act as a seizure gate in the hippocampus thereby reducing epileptic seizures.
*This product is discontinued and has been replaced by #STC-325.
Ziegler L. et al. (2011) Stem Cell Rev. 7, 394.
Alomone Labs Recombinant human FGF-b protein (#F-170) was used to differentiate human embryonic stem cells (SC) into Schwann cells thereby creating a virtually unlimited source of human SC for studies involving nerve regeneration and related diseases.
Kaeser, P.S. et al. (2011) Cell 144, 282.
Synaptic transmissions are initiated by neurotransmitter release caused by Ca2+ influx. The release of neurotransmitter necessitates the colocalization of Ca2+ channels with exocytotic vesicles at the active zone of the presynaptic membrane. Among the different types of voltage-gated Ca2+, N- and P/Q-types are involved in this process.
Rim proteins were shown to be responsible for colocalizing Ca2+ channels and vesicles to the active zone. Indeed, deletion of Rim proteins abolished neurotransmitter release. In addition, CaV2.1 channel was no longer detected at presynaptic terminals, using Alomone Labs Anti-CACNA1A (CaV2.1) Antibody (#ACC-001) in immunofluorescence studies. The localization of CaV2.1 to the active zone is dependent on the PDZ domain.