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Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model.
Brain Res. 2011 Dec 02; 1426:73-85.BR

Abstract

Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of signaling cascade of insulin receptor.

Authors+Show Affiliations

Departamento de Farmacobiología, CINVESTAV, México City, Mexico. poncetere@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22036080

Citation

Ponce-Lopez, Teresa, et al. "Lithium, Phenserine, Memantine and Pioglitazone Reverse Memory Deficit and Restore phospho-GSK3β Decreased in Hippocampus in Intracerebroventricular Streptozotocin Induced Memory Deficit Model." Brain Research, vol. 1426, 2011, pp. 73-85.
Ponce-Lopez T, Liy-Salmeron G, Hong E, et al. Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. Brain Res. 2011;1426:73-85.
Ponce-Lopez, T., Liy-Salmeron, G., Hong, E., & Meneses, A. (2011). Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. Brain Research, 1426, 73-85. https://doi.org/10.1016/j.brainres.2011.09.056
Ponce-Lopez T, et al. Lithium, Phenserine, Memantine and Pioglitazone Reverse Memory Deficit and Restore phospho-GSK3β Decreased in Hippocampus in Intracerebroventricular Streptozotocin Induced Memory Deficit Model. Brain Res. 2011 Dec 2;1426:73-85. PubMed PMID: 22036080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. AU - Ponce-Lopez,Teresa, AU - Liy-Salmeron,Gustavo, AU - Hong,Enrique, AU - Meneses,Alfredo, Y1 - 2011/10/01/ PY - 2011/06/19/received PY - 2011/09/09/revised PY - 2011/09/25/accepted PY - 2011/11/1/entrez PY - 2011/11/1/pubmed PY - 2012/3/6/medline SP - 73 EP - 85 JF - Brain research JO - Brain Res VL - 1426 N2 - Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of signaling cascade of insulin receptor. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/22036080/Lithium_phenserine_memantine_and_pioglitazone_reverse_memory_deficit_and_restore_phospho_GSK3β_decreased_in_hippocampus_in_intracerebroventricular_streptozotocin_induced_memory_deficit_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(11)01803-8 DB - PRIME DP - Unbound Medicine ER -