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Unexpected changes discovered in the pre-symptomatic phase To identify the cellular and molecular changes induced by neurotrophin signalling deficiency, increased DA and ageing that may promote iSPN vulnerability, we examined the transcriptional profile of relevant neurons in the presence and absence of TrkB signalling at 3 months and 8 months

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Such impairments closely parallel the mitochondrial respiratory deficits and elevated oxidative markers reported in cortical and limbic regions of depressed individuals, which would impair energy-dependent neuroplastic processes, intracellular signal transduction cascades, and activity-dependent protein synthesis required for synaptic maintenance, dendritic remodelling, and adaptive circuit function [138, 143]

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