The brainstem is a neglected brain area in neurodegenerative diseases, including Alzheimer's and Parkinson's disease, frontotemporal lobar degeneration and autonomic dysfunction. In Depression, several observations have been made in relation to changes in one particular the Dorsal Raphe Nucleus (DRN) which also points toward as key area in various age-related and neurodevelopmental diseases. The DRN is further thought to be related to stress regulated processes and cognitive events. It is involved in neurodegeneration, e.g., amyloid plaques, neurofibrillary tangles, and impaired synaptic transmission in Alzheimer's disease as shown in our autopsy findings. The DRN is a phylogenetically old brain area, with projections that reach out to a large number of regions and nuclei of the central nervous system, particularly in the forebrain. These ascending projections contain multiple neurotransmitters. One of the main reasons for the past and current interest in the DRN is its involvement in depression, and its main transmitter serotonin. The DRN also points toward the increased importance and focus of the brainstem as key area in various age-related and neurodevelopmental diseases. This review describes the morphology, ascending projections and the complex neurotransmitter nature of the DRN, stressing its role as a key research target into the neural bases of depression.
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http://dx.doi.org/10.1016/bs.pbr.2021.02.003 | DOI Listing |
Alzheimers Dement
December 2024
University of Iowa, Iowa City, IA, USA.
Background: It is increasingly apparent that tau pathology in Alzheimer's disease (AD) begins in the brainstems of middle-aged patients, decades before the onset of symptoms. Most studies are, however, based on brain-bank cohorts and focus on patients dying of natural causes. The true incidence of tau pathology in the brainstem thus remains unclear.
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 PDFBackground: Neuromodulatory subcortical systems (NSS) are affected from the early stages of Alzheimer's Disease (AD) by the accumulation of tau pathology. Increased tau burden within the subcortical nucleus that are in control of sleep and wake regulation may contribute to the breakdown of sleep-wake patterns in AD. A recent postmortem study showed that subcortical wake-promoting neurons were related to sleep phenotypes in AD and PSP, being that greater neuronal count in locus coeruleus (LC), tuberomammillary nucleus (TMN), and lateral hypothalamic area (LHA) associated with a decreased sleep drive (Oh et al.
View Article and Find Full Text PDFAddict Neurosci
June 2024
Bowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Dysregulation of the dopamine (DA) system is a hallmark of substance use disorders, including alcohol use disorder (AUD). Of the DA receptor subtypes, the DA D2 receptors (D2Rs) play a key role in the reinforcing effects of alcohol. D2Rs are expressed in numerous brain regions associated with the regulation of appetitive behaviors.
View Article and Find Full Text PDFToxicology
December 2024
Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano, Torino 10043, Italy; Department of Neuroscience 'Rita Levi Montalcini', University of Torino, Via Cherasco 15, Torino 10126, Italy. Electronic address:
Genistein (GEN) is a phytoestrogen with oestrogen-like activity found in many plants. Classified as an endocrine disruptor, GEN is potentially hazardous, particularly during developmental stages. It induces alterations in anxious behaviour, fertility, and energy metabolism, alongside modifications in specific brain circuits.
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