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Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder.

Yang H, Huh SO, Hong JS - Endocrinol Metab (Seoul) (2015)

Bottom Line: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors.MPEP administration also improved motor coordination in the rotarod test.These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Hallym University College of Medicine, Chuncheon, Korea.

ABSTRACT

Background: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD.

Methods: The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining.

Results: MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice.

Conclusion: This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

No MeSH data available.


Related in: MedlinePlus

Effects of methyl-6-(phenylethynyl)-pyridine (MPEP) on escape latency in the Morris water maze test. Morris water maze training parameters were measured over the course of 5 days at 2 weeks (A) and at 4 weeks (B) after MPEP treatment in both BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice. At 2 weeks, no significant difference in latency time was observed between MPEP-treated and saline-treated B6 mice. When the drug was re-administered 4 weeks after initial administration, the B6 and BTBR group showed no significant difference in latency time. The training trials and probe trials were performed as described in the METHODS. Values are expressed as mean±SEM. aP<0.05; bP<0.01.
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Figure 2: Effects of methyl-6-(phenylethynyl)-pyridine (MPEP) on escape latency in the Morris water maze test. Morris water maze training parameters were measured over the course of 5 days at 2 weeks (A) and at 4 weeks (B) after MPEP treatment in both BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice. At 2 weeks, no significant difference in latency time was observed between MPEP-treated and saline-treated B6 mice. When the drug was re-administered 4 weeks after initial administration, the B6 and BTBR group showed no significant difference in latency time. The training trials and probe trials were performed as described in the METHODS. Values are expressed as mean±SEM. aP<0.05; bP<0.01.

Mentions: The Morris water maze was used to determine the effect of MPEP (10 mg/kg, intraperitoneal) on spatial learning and memory in BTBR and B6 mice. The experimental design is shown in Fig. 1. Escape latency, which was defined as the total time (second) that a mouse spent in the target quadrant before finding the hidden platform, was used as a measure of developing spatial memory. As shown in Fig. 2, MPEP-treated animals exhibited shorter escape latencies as they progressed through training days compared to saline-treated control animals. These data suggest that MPEP (10 mg/kg) administration enhanced the learning and memory of the autism model mice.


Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder.

Yang H, Huh SO, Hong JS - Endocrinol Metab (Seoul) (2015)

Effects of methyl-6-(phenylethynyl)-pyridine (MPEP) on escape latency in the Morris water maze test. Morris water maze training parameters were measured over the course of 5 days at 2 weeks (A) and at 4 weeks (B) after MPEP treatment in both BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice. At 2 weeks, no significant difference in latency time was observed between MPEP-treated and saline-treated B6 mice. When the drug was re-administered 4 weeks after initial administration, the B6 and BTBR group showed no significant difference in latency time. The training trials and probe trials were performed as described in the METHODS. Values are expressed as mean±SEM. aP<0.05; bP<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384677&req=5

Figure 2: Effects of methyl-6-(phenylethynyl)-pyridine (MPEP) on escape latency in the Morris water maze test. Morris water maze training parameters were measured over the course of 5 days at 2 weeks (A) and at 4 weeks (B) after MPEP treatment in both BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice. At 2 weeks, no significant difference in latency time was observed between MPEP-treated and saline-treated B6 mice. When the drug was re-administered 4 weeks after initial administration, the B6 and BTBR group showed no significant difference in latency time. The training trials and probe trials were performed as described in the METHODS. Values are expressed as mean±SEM. aP<0.05; bP<0.01.
Mentions: The Morris water maze was used to determine the effect of MPEP (10 mg/kg, intraperitoneal) on spatial learning and memory in BTBR and B6 mice. The experimental design is shown in Fig. 1. Escape latency, which was defined as the total time (second) that a mouse spent in the target quadrant before finding the hidden platform, was used as a measure of developing spatial memory. As shown in Fig. 2, MPEP-treated animals exhibited shorter escape latencies as they progressed through training days compared to saline-treated control animals. These data suggest that MPEP (10 mg/kg) administration enhanced the learning and memory of the autism model mice.

Bottom Line: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors.MPEP administration also improved motor coordination in the rotarod test.These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Hallym University College of Medicine, Chuncheon, Korea.

ABSTRACT

Background: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD.

Methods: The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining.

Results: MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice.

Conclusion: This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

No MeSH data available.


Related in: MedlinePlus