Rats subjected to a single prolonged episode of maternal deprivation (MD) [24h, postnatal days 9-10] show, later in life, behavioural alterations that resemble specific signs of schizophrenia and other neuropsychiatric signs including increased levels of impulsivity and an apparent difficulty to cope with stressful situations. Some of these behavioural modifications are observable in the periadolescent period. However there is no previous information regarding the possible underlying neurochemical correlates at this critical developmental period. In this study we have addressed the effects of MD on the levels of serotonin (5-HT), dopamine (DA) and their respective metabolites in prefrontal cortex, hippocampus, striatum, midbrain and cerebellum of male and female periadolescent Wistar rats. MD rats showed significantly increased levels of 5-HT in all regions studied with the exception of cerebellum. In addition, MD animals showed increased levels of DA in PFC as well as increased levels of DA and a decrease of DOPAC/DA and HVA/DA ratios in striatum. The effect of MD on the monoaminergic systems was in several cases sex-dependent.
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http://dx.doi.org/10.1016/j.neulet.2010.05.039 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFBackground: Availability of amyloid modifying therapies will dramatically increase the need for disclosure of Alzheimer's disease (AD) related genetic and/or biomarker test results. The 21st Century Cares Act requires the immediate return of most medical test results, including AD biomarkers. A shortage of genetic counselors and dementia specialists already exists, thus driving the need for scalable methods to responsibly communicate test results.
View Article and Find Full Text PDFBackground: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Background: The ability to monitor cognitive trajectories over the course of trials can provide valuable insights into treatment efficacy. However, existing trial methods are limited in monitoring cognition in real-time and at high frequencies. Gameplay-based assessments hold promise as complementary cognitive tools.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Loma Linda University Health, Loma Linda, CA, USA.
Background: Only about 50% of the variance in cognitive decline occurring during Alzheimer's pathogenesis is attributable to standard AD biomarkers (cerebrocortical Aβ, pathological tau, and atrophy) (Tosun et al., Alzheimer's Dement. 18: 1370, 2022).
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