Rationale: APP23 mice are a promising model of Alzheimer's disease, expressing several histopathological, cognitive and behavioural hallmarks of the human condition. A valid animal model should respond to therapeutic interventions in an equivalent manner as human patients.
Objectives: To further validate the APP23 model, we examined whether cognitive deficits could be antagonised by donepezil, rivastigmine, galantamine or memantine, which are approved drugs for symptomatic treatment of dementia.
Methods: Animals were tested at an age at which untreated APP23 mice display severe deficits in visual-spatial learning. Four-month-old APP23 mice and control littermates were administered donepezil (0.3 or 0.6 mg kg(-1)), rivastigmine (0.5 or 1.0 mg kg(-1)), galantamine (1.25 or 2.5 mg kg(-1)), memantine (2 or 10 mg kg(-1)) or saline through daily i.p. injections. After 1 week of treatment, acquisition phase commenced, with daily treatment continuing during cognitive testing.
Results: All cholinesterase inhibitors reduced cognitive deficits with the following optimal daily doses: galantamine 1.25 mg kg(-1), rivastigmine 0.5 mg kg(-1) and donepezil 0.3 mg kg(-1). Higher dosages often did not exert beneficial effects in accordance with inverted U-shaped dose-response curves described for cholinomimetics. Symptomatic efficacy of memantine on cognition was mild, with significant amelioration manifesting during probe trial.
Conclusions: This is the first study to simultaneously evaluate the efficacy of therapeutically relevant doses of these four compounds in one particular learning and memory paradigm, being the Morris water maze. The fact that symptomatic intervention was able to diminish cognitive impairment, substantially adds to the validity of the APP23 model as a valuable tool to evaluate future therapeutic approaches.
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http://dx.doi.org/10.1007/s00213-004-2132-z | DOI Listing |
J Nerv Ment Dis
December 2024
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy.
This review aimed at summarizing the literature evidence on clinical, cognitive, and neurobiological correlates of impaired timing abilities in schizophrenia (SCZ). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search was conducted in PubMed, EMBASE, and PsycInfo by looking at correlates between timing abilities and either symptom severity, cognition, and neurobiological data (imaging and electroencephalography) in individuals with SCZ, without restrictions on study design. A total of 45 articles were selected: associations were identified between impaired timing performance and positive, negative, and disorganization symptoms, as well as with executive functioning, working memory, and attention.
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January 2025
The Second Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, 541199, Guangxi, China.
Type 2 diabetes (T2D) is an important risk factor for brain cognitive impairment, but the specific mechanism is still unclear. The imbalance of gut microbiota under pathological conditions (such as an increase in pathogenic bacteria) may be involved in the occurrence of various diseases. The purpose of this study is to investigate the effect of increased abundance of gut Citrobacter rodentium on cognitive function in T2D mice.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaounde, Cameroon.
Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days.
View Article and Find Full Text PDFNeurol Sci
January 2025
Department of Neurology, Provincial Hospital of Bolzano (SABES- ASDAA), Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität, Bolzano, 39100, Italy.
Introduction: Vortioxetine is a multimodal antidepressant with a high tolerability profile. Recent evidence suggests a role for vortioxetine in improving cognitive function and reducing functional disability linked to depression. We conducted a systematic review on the use of vortioxetine in different neurological disorders.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.
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