Adolescent raloxifene treatment in females prevents cognitive deficits in a neurodevelopmental rodent model of schizophrenia

Felgel-Farnholz, Viktoria; Hlusicka, Elizabeth Barroeta; Edemann-Callesen, Henriette; Garthe, Alexander; Winter, Christine; Hadar, Ravit

doi:10.1016/j.bbr.2022.114276

Cited by 7 publications

(4 citation statements)

References 82 publications

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“…No other drugs such as antidepressants could inverse the behavioral changes of that model. Whatever the neuropsychiatric disorder is, the approach presented here would make it easy and/or cost effective to determine whether some preventive materials including the use of antipsychotics, hormonal agents, and/or anti-inflammatory drugs should be applied to the adolescent poly I:C animals presented here [56,57]. Continuous and alive evaluation might be possible for the evaluation of therapeutic intervention to the model animal of neuropsychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

A Behavioral Test Score Could Be Linked to the Protein Expression Value of p62 and GLAST in the Brain of Mice with Neuropsychiatric Disorders-Related Behaviors

Ikeda¹,

Yoshikawa²,

Taniguchi³

et al. 2023

Preprint

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Neuropsychiatric disorders are globally public-health concern, in which diagnosis might be based on symptoms that often vary across individuals. Schizophrenia is one of the major neuropsychiatric disorders, which may affect millions worldwide. Detection of predictive biomarkers is the most intensively developing approach for the disease. However, the biochemical alterations have not been comprehensively distinguished up to the present time. In addition, there is less confidence of finding a specific biomarker for neuropsychiatric disorders including schizophrenia, but rather a specific characteristic behavioral pattern. Maternal immune activation has been considered to be one of the important factors for the development of neuropsychiatric disorders. Here, the mouse model of neuropsychiatric disorders has been built, in which poly-I:C, sodium dextran sulfate (DSS) and κ-carrageenan (CGN) were used for the maternal immune activation during the pregnancy of individuals. Subsequently, we challenged to link some of biochemical changes of p62 and GLAST in the offspring mice brain to the alteration of several pathological behaviors. Consequently, it has been shown that autophagy might be involved in the development of neuropsychiatric disorders including schizophrenia. To our knowledge, this is the first report of the significant correlation between pathological behavior and the biochemical alterations in neuropsychiatric disorder model animals. The relative ease of conducting these evaluation-tasks would make them useful for testing novel therapeutics designed to ameliorate the symptoms of several psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

A Behavioral Test Score Could Be Linked to the Protein Expression Value of p62 and GLAST in the Brain of Mice with Neuropsychiatric Disorders-Related Behaviors

Ikeda¹,

Yoshikawa²,

Taniguchi³

et al. 2023

Preprint

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“…Early in the 19th century, clinicians formed the so-called estrogen hypothesis , after observations of a possible relationship between the menstrual cycle and psychotic symptoms in schizophrenic female patients [ 31 ]. According to the estrogen hypothesis, which was derived from numerous clinical studies, estrogens act protectively against the development and severity of schizophrenia [ 110 , 111 ]. For instance, earlier menarche, which stimulates the production of estrogens, among other steroid hormones, is associated with later onset of schizophrenia, while post-menopause, associated with a decline in estrogen levels, is characterized by an exacerbation of psychosis symptoms [ 110 , 112 ].…”

Section: Involvement Of Sex Hormonesmentioning

confidence: 99%

Exploring a Possible Interplay between Schizophrenia, Oxytocin, and Estrogens: A Narrative Review

2023

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Schizophrenia is characterized by symptoms of psychosis and sociocognitive deficits. Considering oxytocin’s antipsychotic and prosocial properties, numerous clinical, and preclinical studies have explored the neuropeptide’s therapeutic efficacy. Sex differences in the clinical course of schizophrenia, as well as in oxytocin-mediated behaviors, indicate the involvement of gonadal steroid hormones. The current narrative review aimed to explore empirical evidence on the interplay between schizophrenia psychopathology and oxytocin’s therapeutic potential in consideration of female gonadal steroid interactions, with a focus on estrogens. The review was conducted using the PubMed and PsychINFO databases and conforms to the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines. The results suggest a potential synergistic effect of the combined antipsychotic effect of oxytocin and neuroprotective effect of estrogen on schizophrenia. Consideration of typical menstrual cycle-related hormonal changes is warranted and further research is needed to confirm this assumption.

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“…The dose of raloxifene used in a clinical setting for the treatment of postmenopausal women is 60 mg daily, which corresponds to a dosage of 1 mg/kg. For this reason, we based the study on this concentration and a range of lower concentrations from 1, 10, 100, and 1000 µg/kg in rats in an acute 3-day administration to detect if the treatment with raloxifene produced acute changes in the hemostatic markers [18][19][20][21]. The third group to the sixth to ninth group received E 2 (total n = 60; 1, 10, 100, or 1000 µg/kg).…”

Section: Experimental Designmentioning

confidence: 99%

Hemostatic Effects of Raloxifene in Ovariectomized Rats

Alva-Chavarría,

Soto-Núñez,

Flores-Soto

et al. 2023

Life

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This study aimed to explore the effects of raloxifene (Rx) and estradiol (E2) on prothrombin time (PT), partial thromboplastin time (APTT), coagulation factors (VII, X, XI), and fibrinogen concentrations in rats. Female rats were ovariectomized 11 days prior to starting the treatment. Afterward, they received Rx or E2 (1, 10, 100, and 1000 µg/kg) or propylene glycol (0.3 mL; vehicle, V) subcutaneously for 3 consecutive days. Plasma was collected to measure the hemostatic parameters. Rx significantly increased PT (8%, at 1000 µg/kg; p < 0.05) and APTT at all doses evaluated (32, 70, 67, 30%; p < 0.05, respectively). Rx (1, 10, 100, and 1000 µg/kg) decreased the activity of factor VII by −20, −40, −37, and −17% (p < 0.05), respectively, and E2 increased it by 9, 34, 52, and 29%. Rx reduced factor X activity at 10 and 100 µg/kg doses (−30, and −30% p < 0.05), and E2 showed an increment of 24% with 1000 µg/kg dose only. Additionally, Rx (1, 10, 100 µg/kg) diminished FXI activity (−71, −62, −66; p < 0.05), E2 (1 and 10 µg/kg) in −60 and −38, respectively (p < 0.05), and Rx (1000 µg/kg) produced an increment of 29% (p < 0.05) in fibrinogen concentration, but not E2. Our findings suggest that raloxifene has a protective effect on hemostasis in rats.

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Adolescent raloxifene treatment in females prevents cognitive deficits in a neurodevelopmental rodent model of schizophrenia

Cited by 7 publications

References 82 publications

A Behavioral Test Score Could Be Linked to the Protein Expression Value of p62 and GLAST in the Brain of Mice with Neuropsychiatric Disorders-Related Behaviors

A Behavioral Test Score Could Be Linked to the Protein Expression Value of p62 and GLAST in the Brain of Mice with Neuropsychiatric Disorders-Related Behaviors

Exploring a Possible Interplay between Schizophrenia, Oxytocin, and Estrogens: A Narrative Review

Hemostatic Effects of Raloxifene in Ovariectomized Rats

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