Recently we have shown that in vitro binding of the proximal part of the human tyrosine hydroxylase gene to the nuclear matrix is correlated with its transcriptional activity. The strongest binding potential was predicted by computing for the first intron sequence (Lenartowski & Goc, 2002, Neurosci Lett.; 330: 151-154). In this study a 16 kb fragment of the bovine genomic DNA containing the tyrosine hydroxylase gene was investigated for its affinity to the nuclear matrix. Only a 950 bp fragment encoding the distal part of the first intron, second exon and a few nucleotides of the second intron bound to the nuclear matrix. The binding was independent of the tissue-specific tyrosine hydroxylase gene activation. The fragment was subcloned and sequenced. Computer search pointed to one potential intronic matrix attachment region with two AP1-like sites embedded in the sequence. We conclude that even if the position of the matrix binding region is conserved among the tyrosine hydroxylase genes in mammals, its tissue specificity and/or function is not preserved or is achieved by different mechanisms.
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NPJ Microgravity
January 2025
Department of Biological Science, Boise State University, Boise, ID, 83725, USA.
Systemic mitochondrial dysfunction, dopamine loss, sustained structural changes in the basal ganglia including reduced tyrosine hydroxylase, and altered gait- these effects observed in space-flown animals and astronauts mirrors Parkinson's disease (PD). Evidence of mitochondrial changes in space-flown human cells, examined through the lens of PD, suggests that spaceflight-induced PD-like molecular changes are important to monitor during deep space exploration. These changes, may potentially elevate the risk of PD in astronauts.
View Article and Find Full Text PDFJ Neurosci
January 2025
Leibniz Institute for Neurobiology (LIN), Department of Genetics of Learning and Memory, Magdeburg, 39118 Germany
For a proper representation of the causal structure of the world, it is adaptive to consider both evidence for and evidence against causality. To take punishment as an example, the causality of a stimulus is unlikely if there is a temporal gap before punishment is received, but causality is credible if the stimulus immediately precedes punishment. In contrast, causality can be ruled out if the punishment occurred first.
View Article and Find Full Text PDFBackground: The locus coeruleus (LC), is the first brain region to develop hyperphosphorylated tau (ptau) inclusions in Alzheimer's disease (AD) and undergoes catastrophic degeneration in later stages of the disease. Importantly, the LC is the main noradrenergic nucleus in the brain and source of NE in the forebrain, and dysregulation of the neurotransmitter norepinephrine (NE) is associated with AD symptoms, as its release in the forebrain regulates attention, arousal, stress response, and learning and memory. Moreover, the LC may transmit pathogenic tau to the forebrain via its extensive projections.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Iowa, Iowa City, IA, USA.
Background: The dorsal raphe nucleus (DRN) is the primary source of serotonergic projections to supratentorial structures. We and others have shown that it is selectively vulnerable to tau pathology in both human and mouse models of early AD. Although well characterized in mice, the neurochemical anatomy of the human DRN, and in particular the role of Vesicular glutamate transporter-3 (VGLUT3)-expressing neocortical projection neurons in tau pathology, remains unclear.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Emory University School of Medicine, Atlanta, GA, USA.
Background: Early stages of Alzheimer's disease (AD) are characterized by neuropsychiatric symptoms such as anxiety, apathy, compulsivity, and sleep disturbances, which manifest years before cognitive deficits. It has been hypothesized that dysregulation of the locus coeruleus-norepinephrine (LC-NE) system contributes to these symptoms because (1) the LC is the first site where hyperphosphorylated 'pretangle' tau can be detected in the human brain and (2) NE influences physiological processes such as mood, stress responses, and arousal. To investigate causal relationships between LC tau pathology and neuropsychiatric symptoms, we developed a translationally-relevant model where pathogenic tau is exclusively expressed in mouse LC to recapitulate the 'LC-first' phenomenon.
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