1.Honokiol improves learning and memory impairments induced by scopolamine in mice.
Xian YF1, Ip SP2, Mao QQ1, Su ZR3, Chen JN3, Lai XP3, Lin ZX4. Eur J Pharmacol. 2015 Aug 5;760:88-95. doi: 10.1016/j.ejphar.2015.04.013. Epub 2015 Apr 23.
Honokiol, a lignan isolated from the bark of Magnolia officinalis, has been reported to ameliorate the learning and memory impairments in senesed (SAMP8) mice. However, whether honokiol could improve scopolamine (SCOP)-induced learning and memory deficits in mice is still unknown. In this study, we aimed to investigate whether honokiol could reverse the SCOP-induced learning and memory impairments in mice and to elucidate its underlying mechanisms of action. Mice were given daily intraperitoneal injection of honokiol (10 and 20mg/kg) for 21 consecutive days. The results showed that honokiol significantly improved spatial learning and memory function (as assessed by the Morris water maze test) in the SCOP-treated mice. In addition, treatment with honokiol significantly decreased the protein and mRNA levels of interleukin (IL)-1β and the activity of acetylcholinesterase (AChE), while significantly increased the protein and mRNA levels of IL-10, and the level of acetylcholine (Ach) in the brain of the SCOP-treated mice.
2.Functional characterisation of a tropine-forming reductase gene from Brugmansia arborea, a woody plant species producing tropane alkaloids.
Qiang W1, Xia K1, Zhang Q1, Zeng J1, Huang Y2, Yang C1, Chen M3, Liu X1, Lan X4, Liao Z5. Phytochemistry. 2016 Mar 14. pii: S0031-9422(16)30037-1. doi: 10.1016/j.phytochem.2016.03.008. [Epub ahead of print]
Brugmansia arborea is a woody plant species that produces tropane alkaloids (TAs). The gene encoding tropine-forming reductase or tropinone reductase I (BaTRI) in this plant species was functionally characterised. The full-length cDNA of BaTRI encoded a 272-amino-acid polypeptide that was highly similar to tropinone reductase I from TAs-producing herbal plant species. The purified 29kDa recombinant BaTRI exhibited maximum reduction activity at pH 6.8-8.0 when tropinone was used as substrate; it also exhibited maximum oxidation activity at pH 9.6 when tropine was used as substrate. The Km, Vmax and Kcat values of BaTRI for tropinone were 2.65mM, 88.3nkatmg-1 and 2.93S-1, respectively, at pH 6.4; the Km, Vmax and Kcat values of TRI from Datura stramonium (DsTRI) for tropinone were respectively 4.18mM, 81.20nkatmg-1 and 2.40S-1 at pH 6.4. At pH 6.4, 6.8 and 7.0, BaTRI had a significantly higher activity than DsTRI. Analogues of tropinone, 4-methylcyclohexanone and 3-quinuclidinone hydrochloride, were also used to investigate the enzymatic kinetics of BaTRI.
3.Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.
Xue B1, Chen EC2, He N1, Jin DZ1, Mao LM1, Wang JQ3. Neuropharmacology. 2016 Apr 6. pii: S0028-3908(16)30141-1. doi: 10.1016/j.neuropharm.2016.04.005. [Epub ahead of print]
Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs.
4.Blockade of the dorsal hippocampal dopamine D1 receptors inhibits the scopolamine-induced state-dependent learning in rats.
Piri M1, Rostampour M, Nasehi M, Zarrindast MR. Neuroscience. 2013 Nov 12;252:460-7. doi: 10.1016/j.neuroscience.2013.08.003. Epub 2013 Aug 9.
In the present study, we investigated the possible role of the dorsal hippocampal (CA1) dopamine D1 receptors on scopolamine-induced amnesia as well as scopolamine state-dependent memory in adult male Wistar rats. Animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24h after training for their step-through latency. Results indicated that pre-training or pre-test intra-CA1 administration of scopolamine (1.5 and 3 μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. The pre-training scopolamine-induced amnesia (3 μg/rat) was reversed by the pre-test administration of scopolamine, indicating a state-dependent effect. Similarly, the pre-test administration of dopamine D1 receptor agonist, 1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SKF38393; 1, 2 and 4 μg/rat, intra-CA1), could significantly reverse the scopolamine-induced amnesia.