engleski

Npas4 upregulation in the corticolimbic system in stroke: implications for post-stroke depression

Background: The neuronal Per-Arnt-Sim domain protein 4 (Npas4) is an important transcriptional regulator of synaptic plasticity and cognition. Specifically Npas4 contributes to the homeostatic balance of excitation and inhibition, by regulating the number of inhibitory synapses in an activity and calcium dependant manner. Depression is a major clinical problem post-stroke. Aims: The objective of this study was to characterise the in vivo neuroanatomical expression pattern of the Npas4 protein in a rat model of focal cerebral ischemia. Methods: Animals were subjected to unilateral middle cerebral artery occlusion (MCAo) for 2  h, after which the spatial and neuronal profiles of Npas4 protein expression were analysed by immunohistochemistry at different time points post-reperfusion. Results: Focal cerebral ischemia induced an early, transient and robust upregulation of Npas4 in a brain region-dependent manner involving predominantly principal neurons. Interestingly, we observed a unique differential induction of Npas4 protein expression in corticolimbic regions of the rat brain that are critically linked to cognition and emotion. Discussion: The stroke-induced Npas4 upregulation within the corticolimbic circuitry lead us to ask what possible roles this transcription factor may have in major depression.

Npas4 ; cerebral ischaemia ; rat ; middle cerebral artery occlusion

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