Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP-43 tissue pathology

Autor: Margherita Riggi, Maurizio Romano, Rosario Gulino, Giampiero Leanza, Roberta Pintus, Andrea Valeri, Cecilia Cannarozzo, Gioacchino de Leo
Přispěvatelé: Pintus, Roberta, Riggi, Margherita, Cannarozzo, Cecilia, Valeri, Andrea, de LEO, Gioacchino, Romano, Maurizio, Gulino, Rosario, Leanza, Giampiero
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Alzheimer’s disease
cell transplantation
immunolesion
noradrenaline
rat
working memory
TDP- 43
RRID: AB_2245740
RRID: AB_615042
Pathology
Time Factors
TDP-43
Hippocampus
Dopamine beta-Hydroxylase
Hippocampal formation
Spatial memory
Norepinephrine
0302 clinical medicine
Spatial Memory
Immunotoxins
General Neuroscience
Immunolesion
TDP- 43
Alzheimer's disease
DNA-Binding Proteins
Memory
Short-Term
medicine.anatomical_structure
RRID: AB_615042
Female
medicine.symptom
Alzheimer’s disease
Reinnervation
medicine.medical_specialty
AB_615042 [RRID]
Biology
Antibodies
Statistics
Nonparametric
Lesion
03 medical and health sciences
Neuroblast
Cell transplantation
Noradrenaline
Rat
RRID: AB_2245740
Working memory
Neuroscience (all)
Reaction Time
medicine
Animals
Progenitor cell
Maze Learning
Rats
Disease Models
Animal
030104 developmental biology
Animals
Newborn
Brain Injuries
AB_2245740 [RRID]
030217 neurology & neurosurgery
Zdroj: Journal of Comparative Neurology. 526:1131-1147
ISSN: 0021-9967
DOI: 10.1002/cne.24397
Popis: Extensive loss of noradrenaline-containing neurons and fibers is a nearly invariant feature of Alzheimer’s Disease (AD). However, the exact noradrenergic contribution to cognitive and histo- pathological changes in AD is still unclear. Here, this issue was addressed following selective lesioning and intrahippocampal implantation of embryonic noradrenergic progenitors in developing rats. Starting from about 3 months and up to 12 months post-surgery, animals underwent behav- ioral tests to evaluate sensory-motor, as well as spatial learning and memory, followed by post- mortem morphometric analyses. At 9 months, Control, Lesioned and Lesion1Transplant animals exhibited equally efficient sensory-motor and reference memory performance. Interestingly, working memory abilities were seen severely impaired in Lesion-only rats and fully recovered in Transplanted rats, and appeared partly lost again 2 months after ablation of the implanted neuroblasts. Morphological analyses confirmed the almost total lesion-induced noradrenergic neuronal and terminal fiber loss, the near-normal reinnervation of the hippocampus promoted by the transplants, and its complete removal by the second lesion. Notably, the noradrenergic-rich transplants normalized also the nuclear expression of the transactive response DNA-binding protein 43 (TDP- 43) in various hippocampal subregions, whose cytoplasmic (i.e., pathological) occurrence appeared dramatically increased as a result of the lesions. Thus, integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP-43 tissue pathology.
Databáze: OpenAIRE
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