2004 - Identification of genes regulated by memantine and MK-801 in adult rat brain by cDNA microarray analysis.
1: Neuropsychopharmacology. 2004 Jun;29(6):1070-9. Related Articles, Links
Identification of genes regulated by memantine and MK-801 in adult rat brain by cDNA microarray analysis.
Marvanova M, Lakso M, Wong G.
AI Virtanen Institute for Molecular Sciences, Department of Neurobiology, Laboratory of Functional Genomics and Bioinformatics, University of Kuopio, Kuopio, Finland.
In this study, we monitored gene expression profiles using cDNA microarrays after an acute systemic administration of
the high affinity N-methyl-D-aspartate (NMDA) uncompetitive antagonist MK-801 (1 mg/kg; 4 h),
and the clinically used moderate affinity antagonist memantine (25 mg/kg; 4 h) in adult rat brains.
From a microarray containing 1090 known genes,
13 genes were regulated by both treatments
of which 12 were upregulated
and one was downregulated.
In addition, 28 and 34 genes were regulated (> or = 1.5- or < or = 0.67-fold change) by either memantine or MK-801, respectively.
Genes commonly regulated by both treatments and not previously reported were confirmed by in situ hybridization (ISH) and include
regenerating liver inhibitory factor-1 (RL/IF-1),
GDP-dissociation inhibitor 1 (GDI-1),
neural visinin Ca2+-binding protein 2 (NVP-2),
neuromedin B receptor,
and Na+/K+ transporting ATPase 2beta.
ISH with memantine (5-50 mg/kg) revealed regulation of these genes in other cortical and hippocampal regions.
RL/IF-1 induction occurred at 1 h and returned to basal levels by 8 h, consistent with the profile of an immediate early gene.
Western blot analysis showed increases
(approximately 30-65%)
in GDI-1 protein present in both cytosolic and membrane fractions that were significant in the 84-kDa Rab bound form, suggesting that memantine influences Ras-like GTPase function.
Genes regulated by a 5 mg/kg dose of memantine might be important in its therapeutic effects.
These findings increase the number of known, differentially altered genes after treatment of uncompetitive NMDA receptor antagonists and suggest broader actions of these agents than previously realized. Copyright 2004 Nature Publishing Group
PMID: 14970830 [PubMed - in process]
ncbi.nlm.nih.gov
==============================
Follow-Ups
(NVP-2)
neural visinin Ca2+-binding protein 2 (NVP-2)
1: Neurochem Res. 1999 May;24(5):651-8. Related Articles, Links
Age-related changes in expression of hippocalcin and NVP2 in rat brain.
Furuta Y, Kobayashi M, Masaki T, Takamatsu K.
Department of Physiology, Toho University School of Medicine, Tokyo, Japan.
Expression of hippocalcin and neural visinin-like calcium-binding protein 2 (NVP2) in aging rat brain was investigated by immunoblot and immunohistochemical analyses.
In 3-month old rats,
hippocalcin and NVP2 were present at high concentrations in hippocampal and cerebral pyramidal cells and dentate granule cells, with hippocalcin protein levels being five to ten times higher than NVP2 levels.
Hippocalcin levels in hippocampus and cerebral cortex decreased by approximately 20% at 24 months.
While the number of hippocalcin-positive cells in CA3, dentate gyrus and cerebral cortex were preserved, staining intensity decreased.
In contrast, the number and staining intensity of hippocalcin-positive cells in CA1 were maintained.
NVP2 levels in hippocampus and cerebral cortex decreased by approximately 30% at 24 months.
In cerebral cortex, the number and intensity of NVP2-positive cells decreased.
In CA1 through CA3 and in dentate gyrus, NVP2-positive cell numbers were preserved, but staining intensity decreased.
In summary, the loss of hippocalcin and NVP2 in aging rat brain may be associated with age-related impairment of postsynaptic functions.
PMID: 10344594 [PubMed - indexed for MEDLINE]
too complicated and perhaps not applicable
jbc.org
----------------------
GDP-dissociation inhibitor 1 (GDI-1)
----------------------
Gene Summary for gdi-1
----------------------
wormbase.org
----------------------
neuromedin B receptor,
----------------------
B Receptor, Neuromedin
Cell surface proteins that bind bombesin or closely related peptides with high affinity and trigger intracellular changes influencing the behavior of cells. Gastrin- releasing peptide (GRP); GRP 18-27 (neuromedin C), and neuromedin B are endogenous ligands of bombesin receptors in mammals.
online-medical-dictionary.org
G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [1]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialized database for GPCRs: gpcr.org.
The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [2, 3, 4].
Bombesins are peptide neurotransmitters whose biological activity resides in a common C-terminal sequence, WAXGHXM [5]. In the periphery, bombesin-related peptides stimulate smooth muscle and glandular secretion. In the brain, these peptides are believed to play a role in homeostasis, thermoregulation and metabolism, and have been reported to elicit analgesia and excessive grooming, together with central regulation of a variety of peripheral effects.
Mammalian bombesins are encoded by 2 genes. The preproGRP gene transcript encodes a precursor of 147 amino acids, which gives GRP and GRP18-27. The preproNMB gene transcript encodes a precursor of 117 amino acids, which is metabolised to neuromedin B. Receptors for these peptides have widespread distribution in peripheral tissue. High levels are found in smooth muscle and in the brain.
The neuromedin B receptor has been characterised in rat oesophagus and rat urinary bladder. It is widespread in the CNS, and is found in high levels in olfactory nucleus and thalamic regions, and in lower levels in the frontal cortex, dendate gyrus, amygdala and dorsal raphe. The receptor activates the phosphoinositide pathway through a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class [5].
ebi.ac.uk
These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.
phoenixpeptide.com |
