H3 receptors are abundantly expressed in the prefrontal cortex, an area associated with cognitive performance. While the procognitive effects of H3 receptor antagonists/inverse agonists may depend on alterations to acetylcholine or histamine release, other transmitters involved in cognitive processing such as glutamate and gamma-aminobutyric acid (GABA) may also be involved.
The purpose of the present study was to examine the effects of thioperamide, an H3 receptor antagonist, on extracellular levels of glutamate and GABA in the prefrontal cortex.
By means of in vivo microdialysis
on freely moving Sprague Dawley rats, samples were collected and assayed via high-performance liquid chromatography coupled
to electrochemical detection.
Replacement DMH1 molecular weight of calcium with magnesium revealed that the release of GABA, but not glutamate, was calcium-dependent. Thioperamide (10-20 mg/kg) did not affect basal glutamate or GABA release. Perfusion with a high concentration of potassium (100 mM) increased GABA, but not glutamate, release and thioperamide (20 mg/kg) attenuated the effects of high potassium on GSK621 in vitro GABA release.
These data indicate that H3 receptors in the prefrontal cortex can enhance stimulated GABA release, but do not regulate basal levels of glutamate or GABA.”
“Successful aging depends in part on delaying age-related disease onsets until later in life. Conditions including coronary artery disease, Alzheimer’s disease, prostate cancer, and type 2 diabetes are moderately heritable. Genome-wide association studies have identified many risk associated single-nucleotide polymorphisms for these conditions, but much heritability remains unaccounted check details for. Nevertheless, a great deal is being learned.
Here, we review age-related disease associated single-nucleotide polymorphisms and
identify key underlying pathways including lipid handling, specific immune processes, early tissue development, and cell cycle control.
Most age-related disease associated single-nucleotide polymorphisms do not affect coding regions of genes or protein makeup but instead influence regulation of gene expression. Recent evidence indicates that evolution of gene regulatory sites is fundamental to interspecies differences. Animal models relevant to human aging may therefore need to focus more on gene regulation rather than testing major disruptions to fundamental pathway genes. Recent larger scale human studies of in vivo genome-wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the “”fine tuning”" of protein sequences, as a potentially important factor in decline of cellular function with age. Studies of expression with muscle strength and cognition have shown striking concordance with certain mice models of muscle repair and beta-amyloid phagocytosis respectively.