Down regulation of the c-Fos/MAP kinase signaling pathway during learning memory processes coincides with low GnRH levels in aluminum chloride-induced Alzheimer’s male rats

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.1054, Article 1054
• Main Authors: Lotfizadeh, Reza, Karami, Manizheh, Jalali-Nadoushan, Mohammadreza
• Format: Article
• Language: English
• Subjects: Aluminum; Aluminum chloride; Aluminum Chloride - adverse effects; Alzheimer Disease - chemically induced; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Anesthesia; Animal Anatomy; Animal Biochemistry; Animals; Biomedical and Life Sciences; Brain; Brain - drug effects; Brain - metabolism; c-Fos protein; Dementia disorders; Disease Models, Animal; Down-Regulation - drug effects; Drinking water; Enzyme-linked immunosorbent assay; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - metabolism; Gonadotropins; Histology; Kinases; Learning - drug effects; Life Sciences; Luteinizing hormone; Male; MAP kinase; MAP Kinase Signaling System - drug effects; Memory - drug effects; Morphology; NADPH-diaphorase; Neurodegenerative diseases; Neurons - drug effects; Neurons - metabolism; Nitric Oxide Synthase Type I - metabolism; Nitric-oxide synthase; Original Article; Pituitary (anterior); Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Proto-Oncogene Proteins c-fos - metabolism; Pyramidal cells; Rats; Rats, Wistar; Serum levels; Sex hormones; Signal transduction; Testosterone; Variance analysis
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-024-09987-4

Aluminum chloride (Al) is associated with Alzheimer’s disease (AD) and reproductive disorders. But the relationship between gonadotropin-releasing hormone (GnRH) and c-Fos levels, the end product of MAP-kinase signaling, in AD is unknown, so we aimed to investigate this relationship. We exposed rats to Al dissolved in drinking water (10 and 50 mg/kg) for two and four weeks. The control group received only drinking water. At the end, the blood sample was collected under deep anesthesia and the brain was dissected on ice, and the testicular tissue was fixed in formalin. Amyloid beta (βA) plaques in brain regions and the number of CA1 neurons were evaluated by Congo red staining and cresyl violet staining. Activation of neuronal nitric oxide synthase (nNOS) was studied using NADPH-diaphorase. The levels of c-Fos and testosterone receptors in the target area were examined immunohistochemically. Brain GnRH levels were determined by blotting, and serum levels of gonadotropins and steroids were measured by enzyme-linked immunosorbent assay (ELISA). All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. The accumulation of βA plaque was observed along with a decrease in the number of CA1 pyramidal neurons and a significant decrease in the levels of c-Fos and GnRH in the brains of rats receiving Al, which was aligned with a significant decrease in serum levels of testosterone and LH. This study, for the first time, showed a link between dementia and a concomitant decrease in brain GnRH and c-Fos levels. Graphical Abstract