Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia

Thomas S. Klaric, W. Leong, Martin Lewis, Simon Koblar

Research output: Contribution to conferencePoster

Abstract

The aim of this study was to investigate the expression of the neural activity-dependent transcription factor Neuronal PAS domain protein 4 (Npas4) in various rodent models of stroke. Two different models of stroke were used to induce focal cerebral ischaemia; middle cerebral artery occlusion in rats and Rose Bengal-mediated photochemical ischaemia in mice. Npas4 protein expression in these animals was then investigated using immunohistochemistry and was compared to sham operated animals. Despite the differences in the size and location of the infarcts produced by these two models, the pattern of Npas4 expression that was observed was remarkably similar across both paradigms. Npas4 was found to be rapidly, robustly and transiently up-regulated in the ipsilateral hemisphere following cerebral ischaemia. No expression was observed in the infarct core or the contralateral hemisphere. Npas4 protein expression peaked at 3.5 hours after the onset of ischaemia before gradually returning to baseline levels. In both of the models the same characteristic pattern of Npas4 expression was observed in discrete corticolimbic regions which at times included sites that were undamaged and were some distance away from the lesion. Highest expression was seen in the frontal cortex (layers II/III and V), piriform cortex (layer II), nucleus accumbens, ventral pallidum, amygdala, thalamus and hypothalamus. Interestingly, no up-regulation was observed in the dentate gyrus. Expression of Npas4 was specific to neurons and was not seen in astrocytes, oligodendrocytes or microglial cells. The type of neuron that expressed Npas4 varied in a brain region-dependent manner and it was generally the principal neuron type of each region that expressed Npas4 most frequently. In the frontal and piriform cortices, Npas4 expression was largely associated with excitatory projection neurons, while in the limbic striatum Npas4 was expressed predominantly by inhibitory medium spiny projection neurons. In summary, this study demonstrates that: (1) following cerebral ischaemia there is a unique differential induction of Npas4 protein expression in corticolimbic regions of the rodent brain that are critically linked to cognition and emotion, and (2) this distinctive pattern of expression is reproduced in two distinct models of stroke that differ vastly in the size and location of the resulting infarct. We hypothesise that Npas4 may be part of a transcriptional regulatory programme that is activated within the corticolimbic circuitry following an ischemic insult and that this transcriptional programme is linked to the cognitive and emotional dysfunction seen in the post-stroke mammalian brain.
LanguageEnglish
Publication statusPublished - 11 Nov 2013
EventNeuroscience 2013 - San Diego, United States
Duration: 9 Nov 201313 Nov 2013

Conference

ConferenceNeuroscience 2013
CountryUnited States
CitySan Diego
Period9/11/1313/11/13

Cite this

Klaric, T. S., Leong, W., Lewis, M., & Koblar, S. (2013). Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia. Poster session presented at Neuroscience 2013, San Diego, United States.
Klaric, Thomas S. ; Leong, W. ; Lewis, Martin ; Koblar, Simon. / Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia. Poster session presented at Neuroscience 2013, San Diego, United States.
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title = "Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia",
abstract = "The aim of this study was to investigate the expression of the neural activity-dependent transcription factor Neuronal PAS domain protein 4 (Npas4) in various rodent models of stroke. Two different models of stroke were used to induce focal cerebral ischaemia; middle cerebral artery occlusion in rats and Rose Bengal-mediated photochemical ischaemia in mice. Npas4 protein expression in these animals was then investigated using immunohistochemistry and was compared to sham operated animals. Despite the differences in the size and location of the infarcts produced by these two models, the pattern of Npas4 expression that was observed was remarkably similar across both paradigms. Npas4 was found to be rapidly, robustly and transiently up-regulated in the ipsilateral hemisphere following cerebral ischaemia. No expression was observed in the infarct core or the contralateral hemisphere. Npas4 protein expression peaked at 3.5 hours after the onset of ischaemia before gradually returning to baseline levels. In both of the models the same characteristic pattern of Npas4 expression was observed in discrete corticolimbic regions which at times included sites that were undamaged and were some distance away from the lesion. Highest expression was seen in the frontal cortex (layers II/III and V), piriform cortex (layer II), nucleus accumbens, ventral pallidum, amygdala, thalamus and hypothalamus. Interestingly, no up-regulation was observed in the dentate gyrus. Expression of Npas4 was specific to neurons and was not seen in astrocytes, oligodendrocytes or microglial cells. The type of neuron that expressed Npas4 varied in a brain region-dependent manner and it was generally the principal neuron type of each region that expressed Npas4 most frequently. In the frontal and piriform cortices, Npas4 expression was largely associated with excitatory projection neurons, while in the limbic striatum Npas4 was expressed predominantly by inhibitory medium spiny projection neurons. In summary, this study demonstrates that: (1) following cerebral ischaemia there is a unique differential induction of Npas4 protein expression in corticolimbic regions of the rodent brain that are critically linked to cognition and emotion, and (2) this distinctive pattern of expression is reproduced in two distinct models of stroke that differ vastly in the size and location of the resulting infarct. We hypothesise that Npas4 may be part of a transcriptional regulatory programme that is activated within the corticolimbic circuitry following an ischemic insult and that this transcriptional programme is linked to the cognitive and emotional dysfunction seen in the post-stroke mammalian brain.",
author = "Klaric, {Thomas S.} and W. Leong and Martin Lewis and Simon Koblar",
year = "2013",
month = "11",
day = "11",
language = "English",
note = "Neuroscience 2013 ; Conference date: 09-11-2013 Through 13-11-2013",

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Klaric, TS, Leong, W, Lewis, M & Koblar, S 2013, 'Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia' Neuroscience 2013, San Diego, United States, 9/11/13 - 13/11/13, .

Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia. / Klaric, Thomas S.; Leong, W.; Lewis, Martin; Koblar, Simon.

2013. Poster session presented at Neuroscience 2013, San Diego, United States.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia

AU - Klaric, Thomas S.

AU - Leong, W.

AU - Lewis, Martin

AU - Koblar, Simon

PY - 2013/11/11

Y1 - 2013/11/11

N2 - The aim of this study was to investigate the expression of the neural activity-dependent transcription factor Neuronal PAS domain protein 4 (Npas4) in various rodent models of stroke. Two different models of stroke were used to induce focal cerebral ischaemia; middle cerebral artery occlusion in rats and Rose Bengal-mediated photochemical ischaemia in mice. Npas4 protein expression in these animals was then investigated using immunohistochemistry and was compared to sham operated animals. Despite the differences in the size and location of the infarcts produced by these two models, the pattern of Npas4 expression that was observed was remarkably similar across both paradigms. Npas4 was found to be rapidly, robustly and transiently up-regulated in the ipsilateral hemisphere following cerebral ischaemia. No expression was observed in the infarct core or the contralateral hemisphere. Npas4 protein expression peaked at 3.5 hours after the onset of ischaemia before gradually returning to baseline levels. In both of the models the same characteristic pattern of Npas4 expression was observed in discrete corticolimbic regions which at times included sites that were undamaged and were some distance away from the lesion. Highest expression was seen in the frontal cortex (layers II/III and V), piriform cortex (layer II), nucleus accumbens, ventral pallidum, amygdala, thalamus and hypothalamus. Interestingly, no up-regulation was observed in the dentate gyrus. Expression of Npas4 was specific to neurons and was not seen in astrocytes, oligodendrocytes or microglial cells. The type of neuron that expressed Npas4 varied in a brain region-dependent manner and it was generally the principal neuron type of each region that expressed Npas4 most frequently. In the frontal and piriform cortices, Npas4 expression was largely associated with excitatory projection neurons, while in the limbic striatum Npas4 was expressed predominantly by inhibitory medium spiny projection neurons. In summary, this study demonstrates that: (1) following cerebral ischaemia there is a unique differential induction of Npas4 protein expression in corticolimbic regions of the rodent brain that are critically linked to cognition and emotion, and (2) this distinctive pattern of expression is reproduced in two distinct models of stroke that differ vastly in the size and location of the resulting infarct. We hypothesise that Npas4 may be part of a transcriptional regulatory programme that is activated within the corticolimbic circuitry following an ischemic insult and that this transcriptional programme is linked to the cognitive and emotional dysfunction seen in the post-stroke mammalian brain.

AB - The aim of this study was to investigate the expression of the neural activity-dependent transcription factor Neuronal PAS domain protein 4 (Npas4) in various rodent models of stroke. Two different models of stroke were used to induce focal cerebral ischaemia; middle cerebral artery occlusion in rats and Rose Bengal-mediated photochemical ischaemia in mice. Npas4 protein expression in these animals was then investigated using immunohistochemistry and was compared to sham operated animals. Despite the differences in the size and location of the infarcts produced by these two models, the pattern of Npas4 expression that was observed was remarkably similar across both paradigms. Npas4 was found to be rapidly, robustly and transiently up-regulated in the ipsilateral hemisphere following cerebral ischaemia. No expression was observed in the infarct core or the contralateral hemisphere. Npas4 protein expression peaked at 3.5 hours after the onset of ischaemia before gradually returning to baseline levels. In both of the models the same characteristic pattern of Npas4 expression was observed in discrete corticolimbic regions which at times included sites that were undamaged and were some distance away from the lesion. Highest expression was seen in the frontal cortex (layers II/III and V), piriform cortex (layer II), nucleus accumbens, ventral pallidum, amygdala, thalamus and hypothalamus. Interestingly, no up-regulation was observed in the dentate gyrus. Expression of Npas4 was specific to neurons and was not seen in astrocytes, oligodendrocytes or microglial cells. The type of neuron that expressed Npas4 varied in a brain region-dependent manner and it was generally the principal neuron type of each region that expressed Npas4 most frequently. In the frontal and piriform cortices, Npas4 expression was largely associated with excitatory projection neurons, while in the limbic striatum Npas4 was expressed predominantly by inhibitory medium spiny projection neurons. In summary, this study demonstrates that: (1) following cerebral ischaemia there is a unique differential induction of Npas4 protein expression in corticolimbic regions of the rodent brain that are critically linked to cognition and emotion, and (2) this distinctive pattern of expression is reproduced in two distinct models of stroke that differ vastly in the size and location of the resulting infarct. We hypothesise that Npas4 may be part of a transcriptional regulatory programme that is activated within the corticolimbic circuitry following an ischemic insult and that this transcriptional programme is linked to the cognitive and emotional dysfunction seen in the post-stroke mammalian brain.

M3 - Poster

ER -

Klaric TS, Leong W, Lewis M, Koblar S. Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cortical ischaemia. 2013. Poster session presented at Neuroscience 2013, San Diego, United States.