Cdk5 Contributes to Huntington’s Disease Learning and Memory Deficits via Modulation of Brain Region-Specific Substrates

2017 ◽  
Vol 55 (8) ◽  
pp. 6250-6268 ◽  
Author(s):  
Elena Alvarez-Periel ◽  
Mar Puigdellívol ◽  
Verónica Brito ◽  
Florian Plattner ◽  
James A. Bibb ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Learning And Memory ◽  
Brain Region ◽  
Memory Deficits ◽  
Learning And Memory Deficits

scholarly journals Restoring GABAergic inhibition rescues memory deficits in a Huntington’s disease mouse model

2018 ◽  
Vol 115 (7) ◽  
pp. E1618-E1626 ◽  
Author(s):  
Zahra Dargaei ◽  
Jee Yoon Bang ◽  
Vivek Mahadevan ◽  
C. Sahara Khademullah ◽  
Simon Bedard ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Learning And Memory ◽  
Cognitive Impairments ◽  
Memory Deficits ◽  
Gabaergic Inhibition ◽  
Wild Type ◽  
Excitatory Action ◽  
Excitatory Gaba

Huntington’s disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role of inhibition in learning and memory, we hypothesized that aberrant KCC2 function contributes to the hippocampal-associated learning and memory deficits in HD. We discovered that Htt and KCC2 interact in the hippocampi of wild-type and R6/2-HD mice, with a decrease in KCC2 expression in the hippocampus of R6/2 and YAC128 mice. The reduced expression of the Cl−-extruding cotransporter KCC2 is accompanied by an increase in the Cl−-importing cotransporter NKCC1, which together result in excitatory GABA in the hippocampi of HD mice. NKCC1 inhibition by the FDA-approved NKCC1 inhibitor bumetanide abolished the excitatory action of GABA and rescued the performance of R6/2 mice on hippocampal-associated behavioral tests.

Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease

2009 ◽  
Vol 30 (8) ◽  
pp. 1192-1204 ◽  
Author(s):  
Oliver Ambrée ◽  
Helene Richter ◽  
Norbert Sachser ◽  
Lars Lewejohann ◽  
Ekrem Dere ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Murine Model ◽  
Memory Deficits ◽  
Model Of Alzheimer’S Disease ◽  
Learning And Memory Deficits
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