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Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Increased propensity for amyloidogenesis in male mice
S Shtrasburg1, M Pras, M Dulitzky
1Heller Institute of Medical Research, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel. shmuels@sheba.health.gov.il
Background:
The male sex is a risk factor for reactive amyloidogenesis in several disease entities. Environmental, socioeconomic or genetic factors may underlie this male preponderance. This study was aimed at discovering whether male sex predisposes to reactive amyloidosis also in mice and to elucidate some of the hormonal associations of this risk.
Methods:
Male and female Swiss mice were subjected to an established amyloid induction protocol and the amount of their splenic amyloid was determined and compared. The effect of estrogen, progesterone, testosterone and adrenalin on amyloidogenesis was studied in both sexes by administering these hormnones during amyloid induction and comparing the amount of splenic amyloid of the study mice with the control mice which received the amyloid induction protocol alone.
Results:
Amyloid deposition appeared to be more abundant in male mice. This gender difference was not associated with any of the 3 sex hormones tested. Despite an expected increment, adrenalin caused an attenuation of amyloid deposition.
Conclusions:
The preferential expression of reactive amyloidosis in male mice seems to be unrelated to the common sex hormones. Increased production of other hormones such as adrenalin, or perhaps an augmented susceptibility to their effect, may cause gender differences by suppressing female amyloidogenesis. Our study favors the hypothesis of genetic predisposition as the mechanism leading to sex differences in amyloidogenesis. Further validation of our findings in gonadal ablated models and other amyloid induction protocols is warranted.
Insights
Male mice show higher reactive amyloidosis, but common sex hormones don't explain this. Adrenalin may suppress amyloidosis in females, suggesting genetic factors influence sex differences in amyloidogenesis.
Area of Science:
- Biomedical Research
- Endocrinology
- Pathology
Background:
- Male sex is a known risk factor for reactive amyloidogenesis.
- Potential underlying factors include environmental, socioeconomic, or genetic influences.
- This study investigates male predisposition to reactive amyloidosis in mice and hormonal associations.
Purpose of the Study:
- To determine if male mice exhibit a predisposition to reactive amyloidosis.
- To explore the role of estrogen, progesterone, and testosterone in sex-based differences in amyloidogenesis.
- To investigate the influence of adrenalin on amyloid deposition in both sexes.
Main Methods:
- Male and female Swiss mice underwent an amyloid induction protocol.
- Splenic amyloid levels were quantified and compared between sexes.
- Hormonal effects (estrogen, progesterone, testosterone, adrenalin) were assessed by administration during induction.
Main Results:
- Amyloid deposition was more pronounced in male mice compared to females.
- The observed gender difference was not linked to the tested sex hormones (estrogen, progesterone, testosterone).
- Adrenalin administration, contrary to expectations, attenuated amyloid deposition.
Conclusions:
- The higher incidence of reactive amyloidosis in males appears independent of common sex hormones.
- Adrenalin or other hormones may play a role in sex differences by suppressing female amyloidogenesis.
- Genetic predisposition is favored as the primary mechanism for sex differences in amyloidogenesis, warranting further study in gonadal ablated models.
