Rodent Models as Tools for Discovering Novel Therapeutic Targets in the Brain: The Case of Epilepsy

Botterill, Justin J.; Guskjolen, Axel; Kalynchuk, Lisa E.; Caruncho, Héctor J.

doi:10.1002/9781118185537.ch13

Cited by 2 publications

(2 citation statements)

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“…NPY Y 2 R has been implicated with several neuronal excitability (Silva et al, 2005) and cognitive processes (Botterill et al, 2015;Hörmer et al, 2018;Verma et al, 2019); this suggests a functional role on spatial orientation. Specifically, when the NPY is applied before the memory training, it seems to impair the acquisition and retention of spatial memory, apparently via presynaptic Y 2 R-mediated inhibition of synaptic glutamatergic transmission and LTP induction, [see review by Gøtzsche and Woldbye (2016)].…”

Section: Hippocampal Npy Y 2 R Blockade Before Spatial Memory Retrieval Changes Metabolic Activity In the Dorso-ventral Hippocampus Inframentioning

confidence: 99%

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Méndez-Couz

González-Pardo

Árias

et al. 2021

Preprint

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IntroductionThe neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y2 receptor (Y2R) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on Y2R remain unclear.MethodsHere, we examined the involvement of the hippocampal NPY Y2R in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions.ResultsThe acute blockade of NPY Y2R significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies.ConclusionsThese findings suggest that the NPY hippocampal system, through its Y2R receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by Y2R modulation of long-term potentiation and long-term depression.HighlightsUnder hippocampal Y2R antagonism, place preference memory retrieval is enhancedSpatial retrieval enhancement under Y2R blockade is correlated with changes in regional brain energy metabolismEnhanced retrieval associated CCO activity increases in the dorsal DG, while decreasing in the ventral CA1, IL cortex and mammillary bodiesY2R exert control over patterns of brain activation that are relevant for spatial memory expression

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Section: Hippocampal Npy Y 2 R Blockade Before Spatial Memory Retrieval Changes Metabolic Activity In the Dorso-ventral Hippocampus Inframentioning

confidence: 99%

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Méndez-Couz

González-Pardo

Árias

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…One possible mechanism is the action of NPY on other neurotransmitter systems (like catecholamines) and its regulation of glucose metabolism in both neurons and glial cells (Huang et al, 2021). NPY Y 2 R has been implicated with several neuronal excitability (Silva et al, 2005) and cognitive processes (Botterill et al, 2015;Hörmer et al, 2018;Verma et al, 2019); this suggests a functional role on spatial orientation. Specifically, when the NPY is applied before the memory training, it seems to impair the acquisition and retention of spatial memory, apparently via presynaptic Y 2 R-mediated inhibition of synaptic glutamatergic transmission and LTP induction, [see review by Gøtzsche and Woldbye (2016)].…”

Section: Hippocampal Npy Y 2 R Blockade Before Spatial Memory Retriev...mentioning

confidence: 99%

Hippocampal neuropeptide Y2 receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Méndez-Couz

González-Pardo

Árias

et al. 2022

Neurobiology of Learning and Memory

View full text Add to dashboard Cite

Rodent Models as Tools for Discovering Novel Therapeutic Targets in the Brain: The Case of Epilepsy

Cited by 2 publications

References 122 publications

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal neuropeptide Y2 receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

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Rodent Models as Tools for Discovering Novel Therapeutic Targets in the Brain: The Case of Epilepsy

Cited by 2 publications

References 122 publications

Hippocampal Neuropeptide Y2receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal Neuropeptide Y2receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal neuropeptide Y2 receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

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Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism