Estrogen and lithium: Facilitating factors involved in brain cell signaling pathways

Learning and memory in adult females decline during menopause and estrogen replacement therapy is commonly prescribed during menopause. Post-menopausal women tend to suffer from depression and are prescribed antidepressants – in addition to hormone therapy. Estrogen replacement therapy is a topic that engenders debate since several studies contradict its efficacy as a palliative therapy for cognitive decline and neurodegenerative diseases. Signaling transduction pathways can alter brain cell activity, survival, and morphology by facilitating transcription factor DNA binding and protein production. The steroidal hormone estrogen and the anti-depressant drug lithium interact through these signaling transduction pathways facilitating transcription factor activation. The paucity of data on how combined hormones and antidepressants interact in regulating gene expression led me to hypothesize that in primary mixed brain cell cultures, combined 17β-estradiol (E2) and lithium chloride (LiCl) (E2/LiCl) will alter genetic expression of markers involved in synaptic plasticity and neuroprotection. Results from these studies indicated that a 48 h treatment of E2/LiCl reduced glutamate receptor subunit genetic expression, but increased neurotrophic factor and estrogen receptor genetic expression. Combined treatment also failed to protect brain cell cultures from glutamate excitotoxicity. If lithium facilitates protein signaling pathways mediated by estrogen, can lithium alone serve as a palliative treatment for post-menopause? This question led me to hypothesize that in estrogen-deficient mice, lithium alone will increase episodic memory (tested via object recognition), and enhance expression in the brain of factors involved in anti-apoptosis, learning and memory. I used bilaterally ovariectomized (bOVX) C57BL/6J mice treated with LiCl for one month. Results indicated that LiCl-treated bOVX mice increased performance in object recognition compared with non-treated bOVX. Increased performance in LiCl-treated bOVX mice coincided with augmented genetic and protein expression in the brain. Understanding the molecular pathways of estrogen will assist in identifying a palliative therapy for menopause-related dementia, and lithium may serve this purpose by acting as a selective estrogen-mediated signaling modulator.

Pairing Repeated Reading and Systematic Error Correction: Impact on Fluency of 18 Year Old Students on a Small Caribbean Island

This study investigates the impact of a combined treatment of Systematic Error Correction and Repeated Reading on reading rate and errors for 18 year olds with undiagnosed reading difficulties on a Caribbean Island. In addition to direct daily measures of reading accuracy, the Reading Self Perception Scale was administered to determine whether the intervention was associated with changes in the way the student perceives himself as a reader.

Estrogen and Lithium: Facilitating Factors Involved in Brain Cell Signaling Pathways

Learning and memory in adult females decline during menopause and estrogen replacement therapy is commonly prescribed during menopause. Post-menopausal women tend to suffer from depression and are prescribed antidepressants – in addition to hormone therapy. Estrogen replacement therapy is a topic that engenders debate since several studies contradict its efficacy as a palliative therapy for cognitive decline and neurodegenerative diseases. Signaling transduction pathways can alter brain cell activity, survival, and morphology by facilitating transcription factor DNA binding and protein production. The steroidal hormone estrogen and the anti-depressant drug lithium interact through these signaling transduction pathways facilitating transcription factor activation. The paucity of data on how combined hormones and antidepressants interact in regulating gene expression led me to hypothesize that in primary mixed brain cell cultures, combined 17beta-estradiol (E2) and lithium chloride (LiCl) (E2/LiCl) will alter genetic expression of markers involved in synaptic plasticity and neuroprotection. Results from these studies indicated that a 48 h treatment of E2/LiCl reduced glutamate receptor subunit genetic expression, but increased neurotrophic factor and estrogen receptor genetic expression. Combined treatment also failed to protect brain cell cultures from glutamate excitotoxicity. If lithium facilitates protein signaling pathways mediated by estrogen, can lithium alone serve as a palliative treatment for post-menopause? This question led me to hypothesize that in estrogen-deficient mice, lithium alone will increase episodic memory (tested via object recognition), and enhance expression in the brain of factors involved in anti-apoptosis, learning and memory. I used bilaterally ovariectomized (bOVX) C57BL/6J mice treated with LiCl for one month. Results indicated that LiCl-treated bOVX mice increased performance in object recognition compared with non-treated bOVX. Increased performance in LiCl-treated bOVX mice coincided with augmented genetic and protein expression in the brain. Understanding the molecular pathways of estrogen will assist in identifying a palliative therapy for menopause-related dementia, and lithium may serve this purpose by acting as a selective estrogen-mediated signaling modulator.

Gender differences in behavioral and psychosocial correlates of substance abuse among adolescents in residential treatment

This dissertation reports the results of a study that examined differences between genders in a sample of adolescents from a residential substance abuse treatment facility. The sample included 72 males and 65 females, ages 12 through 17. The data were archival, having been originally collected for a study of elopement from treatment. The current study included 23 variables. The variables were from multiple dimensions, including socioeconomic, legal, school, family, substance abuse, psychological, social support, and treatment histories. Collectively, they provided information about problem behaviors and psychosocial problems that are correlates of adolescent substance abuse. The study hypothesized that these problem behaviors and psychosocial problems exist in different patterns and combinations between genders.^ Further, it expected that these patterns and combinations would constitute profiles important for treatment. K-means cluster analysis identified differential profiles between genders in all three areas: problem behaviors, psychosocial problems, and treatment profiles. In the dimension of problem behaviors, the predominantly female group was characterized as suicidal and destructive, while the predominantly male group was identified as aggressive and low achieving. In the dimension of psychosocial problems, the predominantly female group was characterized as abused depressives, while the male group was identified as asocial, low problem severity. A third group, neither predominantly female or male, was characterized as social, high problem severity. When these dimensions were combined to form treatment profiles, the predominantly female group was characterized as abused, self-harmful, and social, and the male group was identified as aggressive, destructive, low achieving, and asocial. Finally, logistic regression and discriminant analysis were used to determine whether a history of sexual and physical abuse impacted problem behavior differentially between genders. Sexual abuse had a substantially greater influence in producing self-mutilating and suicidal behavior among females than among males. Additionally, a model including sexual abuse, physical abuse, low family support, and low support from friends showed a moderate capacity to predict unusual harmful behavior (fire-starting and cruelty to animals) among males. Implications for social work practice, social work research, and systems science are discussed. ^