Enhancing cognition through pharmacological and environmental interventions: Examples from preclinical models of neurodevelopmental disorders

Abstract

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Dopamine D1 and Glutamate Receptors Co-operate With Brain-Derived Neurotrophic Factor (BDNF) and TrkB to Modulate ERK Signaling in Adult Striatal Slices

“…The extracellular-signal regulated kinase (ERK) cascade belongs to the mitogen-activated protein kinase (MAPK) superfamily, a class of highly conserved serine/threonine kinases, originally implicated in cell proliferation, survival, and apoptosis (Mebratu and Tesfaigzi, 2009;Roskoski, 2012). Over the last two decades, considerable attention has been pointed to the multifaceted role of this signaling cascade in a variety of brain functions, from learning and consolidation of long-term memories to drug addiction and neuropsychiatric disorders (Mazzucchelli et al, 2002;Trifilieff et al, 2007;Hart and Balleine, 2016;Krawczyk et al, 2016;Borrie et al, 2017;Morè et al, 2020).…”

The relevance of a rodent cohort in the Consortium on Individual Development

“…For instance, many studies point to a higher risk on impaired mnemonic function, aberrant reward-based decision-making and enhanced anxiety-related behavior after early life adversity ( Delavari et al, 2016 ; Herzberg and Gunnar, 2019 ; Woldemichael et al, 2014 ). Conversely, a favorable rearing environment might have beneficial effects on cognition, emotionality and response to stress ( Cirulli et al, 2010 ; Morè et al, 2019 ).…”

A proteomic signature for CNS adaptations to the valence of environmental stimulation

“…In mammals, the Ras-ERK pathway has been proposed to be the primary mediator of in vivo adaptations to the environment [4][5][6]. Previous work in mice has shown that much of the cognitive enhancing effects of environmental enrichment act via the downstream Ras-ERK signalling kinase MSK1 and a relevant portion of spatial cognitive flexibility is mediated by the transcription factor CREB phosphorylation [4,7,8]. It remains still an open question whether some key aspects of spatial learning & memory and procedural learning might be governed by different molecular pathways than those controlling social cognition [9].…”

“…[7,[34][35][36][37][38]. LC-MS/MS analysis identified 977 proteins from the hippocampi and frontal lobes of mice from positively and negatively enriched groups and determined their normalised abundance (see supplementary data for raw data tables).Of the total number of proteins identified, none were increased or decreased in the hippocampus (supplementary data).…”

“…J o u r n a l P r e -p r o o fOther processes identified centred on ATPase activity and transmembrane proton transport, which included components of the vacuolar-type H + -ATPase complex (Figure 3A). Moreover, a number of upregulated calcium-related proteins were identified to be associated with the presynaptic cytosol (calbindin 1, protein kinase c alpha, and protein kinase c epsilon) in frontal lobes due to negative enrichment(Figure 3 D).Whilst the Ras-ERK pathway is thought to control transcriptional events in Neuro Developmental Disorders and ageing[7,[39][40][41], little is known about the downstream mechanisms. However, metabolic regulation of mitochondrial ATP production lies central to neuronal and glial function and processes related to neurotransmission[42][43][44].Mitochondria are thought to play a pivotal role in neuronal function and synaptic regulation in neuropsychiatric disorders[45,46].Furthermore, mitochondria and reactive oxygen species (ROS) have been implicated in the developmental control of neuronal processes such as synapse pruning [47].…”