ERK1, 2, and 5 expression and activation in dopaminergic brain regions during postnatal development

Abstract

Degeneration and dysfunctioning of dopaminergic neurons in the midbrain have been associated with serious neurodegenerative and neuropsychiatric disorders. Elucidating the underlying neurobiology of these neurons during early postnatal development may provide important information regarding the etiology of these disorders. Cellular signaling pathways have been shown to regulate postnatal neuronal development. Among several signaling pathways, extracellular-regulated mitogen kinases (ERK) 1, 2, and 5 have been shown to be crucial for the survival and function of dopaminergic neurons. In this study, the basal expression and activation of ERK1, 2, and 5 were studied during postnatal development in regions rich in DA cells and terminals. In the striatum (STR) and ventral mesencephalon regions of the substantia nigra (SN) and ventral tegmental area (VTA), ERK5 expression and activation were high during early postnatal days and declined with aging. Interestingly, sharp increases in phosphorylated or activated ERK1 and ERK2 were observed at postnatal day (PND) 7 in the SN and VTA. In contrast, in the STR, the levels of phosphorylated ERK1 and 2 were significantly higher at PND0 than at any other PND examined. Overall, the understanding of alterations in ERK signaling in regions rich in DA cells and DA terminals during postnatal neuronal development may provide information about their role in regulation of dopamine neuronal development which may ultimately provide insight into the underlying mechanisms of dopamine neurodegeneration.

Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2-dependent mechanism

“…While others have noted increases and decreases in ERK1/2 activation following resveratrol administration in the hippocampus [12, 28], these are the first studies to examine the effects of resveratrol or pinostilbene on ERK1/2 activity in the striatum. This data complements work published by Parmar and colleagues demonstrating that ERK1/2 is important for DA cell survival [78] and possible DAergic region development [79]; therefore, the increase in the ERK1/2 by these phytochemicals could be contributing to the healthy state or functioning of DAergic neurons.…”

Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature

“…The MAPK family is an important signaling pathway of Nox2-derived ROS involved in many brain physiological and pathological processes, including maintenance of neuronal viability, vascular alteration, and apoptosis (34–37). Increased ERK1/2 expression has been found in age-related neurodegenerative abnormalities (36). In support of these previous studies, we found Nox2-dependent ERK1/2 activation together with a significant increase in brain cell DNA damage, i.e., increased γH2AX and p53, in the midbrains of aging WT mice and elderly humans.…”

Milk’s Role as an Epigenetic Regulator in Health and Disease

“…Activation of dopaminergic signaling plays an important role in the midbrain and frontal cortex during postnatal development [235,236]. Midbrain dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area regulate extrapyramidal movement and important cognitive functions, including motivation, habit learning, and reward associations [237].…”