51猎奇

Salahadin Lotfi received a Sigma Xi grant for a study on emotional working memory training of anxious individuals

Sala Lotfi

Sigma_X_logo

Sala Lotfi, a grad student working with Dr. Hanjoo Lee, was recently awarded a grant-in-aid of research from the Sigma Xi, titled 鈥淚mproving inhibitory control through emotional working memory training of anxious individuals鈥�. This grant aims to cover the expenses of the research project, which Sala is currently working on under the supervision of Drs. Hanjoo Lee and Christine Larson.

It has been shown that trait anxiety is associated with an excessive allocation of attentional resources toward threat-related stimuli. Also, the extent to which working memory training can enhance the suppression of negative automatic thoughts has not been clearly shown. Sala鈥檚 study will shed light on the important role of working memory (WM) on anxiety problems using the two advanced research methods such as computerized WM training focused on inhibitory control, and online monitoring of neurocognitive activities via the EEG/ERP technique.

New Journal of Neuroscience paper by Dr. Frick and graduate student Jen Tuscher solves an old mystery in behavioral endocrinology

Dr Frick standing and smiling in an office with bookshelves, framed photos, and a red accent wal

Researchers have known for two decades that the sex steroid hormone 17beta-estradiol alters the morphology of neurons in the hippocampus and prefrontal cortex, parts of the brain necessary for memory formation that deteriorate in aging and Alzheimer鈥檚 disease. In particular, estradiol increases the density of spines on the dendrites of excitatory neurons in the hippocampus and cortex. Dendritic spines are associated with greater synaptic plasticity, so an increase in dendritic spines is thought to underlie the enhanced memory observed after estradiol treatment in rodents. However, it has been unknown how estradiol regulates dendritic spines. A recent study published in The Journal of Neuroscience by Dr. Karyn Frick and graduate student Jennifer Tuscher, along with collaborators in New York, sheds light on this mystery. The Frick lab previously showed in mice that the cell-signaling molecules ERK and mTOR played crucial roles in the ability of estradiol to enhance the kinds of spatial memory and object recognition memories mediated by the hippocampus. It turns out that activation of ERK or mTOR signaling in the hippocampus is also necessary for estradiol to increase dendritic spine density not only in the hippocampus, but also the prefrontal cortex. Thus, this study is the first to show that cell signaling regulates estradiol-induced spine formation in the hippocampus, and that this spine formation drives spinogenesis in the prefrontal cortex.

These findings are significant because they provide novel insights into the molecular mechanisms through which estradiol mediates the function of the hippocampus and prefrontal cortex. Women are at greater risk of developing age-related memory decline and dementia than men, likely due to estradiol loss at menopause. Because age-related impairments in hippocampal and cortical function are associated with memory decline, it is important to understand how estradiol regulates the function of these brain regions in females. This knowledge could facilitate the development of new therapies to prevent or reduce memory dysfunction in older women.

Jaekyoon Kim published a new study on the role of G-protein-coupled Estrogen Receptor in female mice hippocampal memory.

Jae Kyoon Kim

G-protein-coupled Estrogen Receptor (GPER/GPR30): The Estrogen Receptor That Doesn’t Act Like an Estrogen Receptor / Kim J, Szinte JS, Boulware MI, Frick KM. 17尾-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms. J Neurosci. 2016 Mar 16;36(11):3309-21. doi: 10.1523/JNEUROSCI.0257-15.2016.

Jaekyoon Kim published a new study in the journal of Neuroscience that aims to investigate the role of G-protein-coupled Estrogen Receptor (GPER/GPR30) in female mice hippocampal memory. The ability of 17尾-estradiol (E2) to enhance hippocampal object recognition and spatial memory depends on rapid activation of extracellular signal-regulated kinase (ERK) in the dorsal hippocampus (DH). Although this activation can be mediated by the intracellular estrogen receptors ER伪 and ER尾, little is known about the role that the membrane estrogen receptor GPER plays in regulating E2-mediated memory formation. In this study, although GPER activation did enhance object recognition and spatial memory, it did so by activating different cell-signaling mechanisms from ER伪, ER尾, or 17尾-estradiol. The data indicate that GPER regulates memory independently from ER伪 and ER尾 by activating c-Jun N-terminal kinase (JNK) signaling, rather than ERK signaling. Thus, the findings suggest that GPER in the DH may not function as an estrogen receptor to regulate object recognition and spatial memory.

Jaekyoon examined whether the putative membrane estrogen receptor GPER acts like the classical estrogen receptors, ER伪 and ER尾, to facilitate hippocampal memory in female mice. These data indicate that 17尾-estradiol and GPER independently regulate hippocampal memory, and suggest that hippocampal GPER may not function as an estrogen receptor in the dorsal hippocampus. These findings are significant because they provide novel insights about the molecular mechanisms through which 17尾-estradiol modulates hippocampal memory. Jaekyoon believes this can reveal a novel drug targets for reducing age-related memory decline in women.

Jen Tuscher’s new study suggests that estrogenic regulation of the dorsal hippocampus influences spinogenesis in the mPFC.

Jennifer Tuscher

Estrogenic regulation of spinogenesis in the dorsal hippocampus and medial prefrontal cortex; Journal of Neuroscience (36: 1483-9)

Jennifer Tuscher is the first author on a recently published article in the Journal of Neuroscience (36: 1483-9) showing that direct infusion of 17b-estradiol into the dorsal hippocampus not only increased spine density in CA1, but also in the medial prefrontal cortex (mPFC), suggesting that estrogenic regulation of the dorsal hippocampus influences spinogenesis in the mPFC. Tuscher and co-authors Maya Frankfurt, Vicky Luine, and Karyn Frick also found that the estradiol-mediated increases in CA1 and mPFC spine density were blocked by inhibition of ERK and mTOR cell signaling in the dorsal hippocampus. These findings fit with previous work from the Frick lab showing that activation of extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling in the dorsal hippocampus is necessary for estradiol to enhance memory consolidation. Collectively, the new findings provide the first evidence that estradiol infusion in the hippocampus can regulate spinogenesis in the mPFC and that estradiol-mediated spinogenesis in the hippocampus and mPFC depends on rapid activation of cell signaling pathways, which the investigators believe may support the memory-enhancing effects of estradiol.

This research sheds new light on the molecular mechanisms underlying estradiol-induced spine changes, and suggests that the DH and mPFC may interact to mediate the memory-enhancing effects of estradiol.

Jen Turkel works with Coco and Bijou to help individuals overcome their fear

Jen Turkel

Jen聽Turkel is currently working on her dissertation project that aims to investigate the role of attentional processes in exposure therapy. She is accomplishing this by combining a computer-based cognitive training program with a single session of in-vivo exposure therapy for individuals with a fear of spiders. The experiment includes computerized eye-tracking and reaction-time based tasks, physiological recording, self-report assessments, and behavioral approach and exposure tasks that involve live tarantulas (Coco and Bijou). Coco

This research is both theoretically and clinically significant considering the theories behind attention bias modification (ABM) and exposure therapy have contradictory positions on where attention should be allocated for maximizing the efficacy of the intervention. Findings from this study may provide insight into how attentional allocation patterns may affect the outcome of exposure therapy and potentially lead to improvements in this area. Additionally, the use of computerized cognitive training may address limitations of behavior therapy such as the potential for relapse and the challenge of undergoing the intensity of the exposure procedure.

Dr. Lisdahl and her students published a new study on the effects of regular cannabis use on neurocognition in young people.

Lisdahl seated at a desk with dual monitors displaying research slides on MJ use and brain parietal volumes

Lisdahl, K.M., Wright, N.E., Kirchner-Medina, C., Maple, K.E., Shollenbarger, S. (2014). Considering cannabis: The effects of regular cannabis use on neurocognition in adolescents and young adults. Current Addiction Reports, 1(2), 144-156.

Thirty-six percent of high school seniors have used cannabis in the past year, and an alarming 6.5% smoked cannabis daily, up from 2.4% in 1993 (Johnston et al., 2013). Adolescents and emerging adults are undergoing significant neurodevelopment and animal studies suggest they may be particularly vulnerable to negative drug effects. In this review, we will provide a detailed overview of studies outlining the effects of regular (at least weekly) cannabis use on neurocognition, including studies outlining cognitive, structural and functional findings. We will also explore the public health impact of this research.

As many states have recently legalized recreational and medicinal cannabis use, it is important to understand the potential impact of cannabis use on neurocognition. This review highlights the relationship between cannabis use and neurocognition in adolescents and young adults.

Coming out to family and friends as bisexually-identified young adult women: A discussion of homophobia, biphobia, and heteronormativity

Rachael Wandrey published a new study in the Journal of Bisexuality. Wandrey, R.L., Mosack, K.E., & Moore, E. (2015). Coming out to family and friends as bisexually-identified young adult women: A discussion of homophobia, biphobia, and heteronormativity. Journal of Bisexuality, 15 (2), 204-229.

Although coming out is considered a crucial part of minority sexual identity development, research concerning bisexual women’s coming out experiences is limited. Nevertheless, bisexual women encounter unique stigma and challenges that warrant specific attention. Seventeen young adult women participated in individual, open-ended qualitative interviews about their bisexual identity development. Our inductive thematic analysis of participants’ coming out experiences and perspectives revealed important themes related to the unique aspects of coming out as young bisexual women. Themes included 1) the presence of both homophobia and biphobia, 2) the use of alternate identity terms to combat biphobia, 3) the preference to approach coming out in a casual manner, 4) the ability to pass as heterosexual or lesbian when it fits the situation, and 5) the resolute rejection of the disclosure imperative, among others. We discuss these findings in the context of gender, homophobia, biphobia, and heteronormativity.

A new study showing the association between poorer frontolimbic white matter integrity and chronic cannabis use

Man smiling at his desk with dual monitors displaying colorful brain scan images

Skyler Shollenbarger is the first author of a new study published in Clinical-Neuroimage. Shollenbarger, S.G., Price, J., Wieser, J., Lisdahl, K. L. (2015). Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults. Clinical-Neuroimage, (8), 117-125.doi:10.1016/j.nicl.2015.03.024.

The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms.

Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18鈥�25). Multiple regressions examined the independent and interactive effects of variables on WM integrity.

WM_results

Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group 鈭� FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC.
Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users.

In conclusion, this study found that regular cannabis use is associated with poorer frontolimbic WM integrity, and these findings were moderated by the FAAH genotype. This reduced WM integrity was associated with negative mood and greater apathy symptoms in cannabis users. As use is predicted to rise in youth ( Caulkins et al., 2012) in the context of decreases in perceived risk ( Johnston et al., 2013), it remains an important public health priority to delay the onset of regular cannabis use until neuronal maturation has been reached (see Lisdahl et al., 2013).

“Effects of new HDAC inhibitors on hippocampal function and memory formation”. Dr. Frick received a 51猎奇 Research Foundation Catalyst Grant

Dr Frick standing and smiling in an office with bookshelves, framed photos, and a red accent wal

Pharmacological interventions that prevent or delay memory loss associated with aging would substantially improve quality of life for affected individuals, increase their productivity, and decrease the health care costs for those with memory loss and dementia. Memory deficits are common to aging and neurodegenerative diseases like Alzheimer鈥檚 disease. Because the U.S. population is rapidly aging, the incidence of memory dysfunction will increase exponentially. Although memory dysfunction is a significant impediment to independent living and diminishes workforce productivity, few treatments effectively prevent or reverse memory impairments. An extremely promising avenue for such treatment is the use of histone deacetylase inhibitor drugs (HDACis).

A promising avenue for such treatment is the use of histone deacetylase inhibitor drugs. Dr. Frick and others have found that HDACis increase synaptic plasticity in the brain and enhance learning and memory in mouse models of Alzheimer鈥檚 disease1, 2. These findings raise the possibility that HDACis could reduce cognitive impairment in the elderly and patients with neurodegenerative diseases. Small molecule HDACis, such as FK228 and SAHA (Fig 1), have been approved for the treatment of certain cancers, but their effectiveness is limited by unwanted toxicity and/or poor solubility. Dr. Hossain and colleagues have synthesized a small library of potent HDACi molecules that show good solubility and low toxicity in mice (Table 1). Here, we will test the ability of 3 lead compounds to enhance the formation of two types of memory. Thus, the goal of this study is to test the effects of novel, non-toxic HDACi compounds on memory in a well-established mouse model of memory formation with which the PI has extensive experience. These proof-of-principle data are needed to apply for federal and foundation funding to conduct more extensive testing, a patent application, and to eventually attract licensing partners such as Merck or Takeda that are active in Alzheimer鈥檚 drug research.

This study is designed to develop and test the effects of novel, non-toxic histone deacetylase inhibitor compounds on memory in order to reduce memory decline in aging and Alzheimer’s disease.

Do sex steroid hormones matter for learning and memory? A review on estrogenic regulation of hippocampal function in male and female rodents.

Dr Frick at her desk with a computer screen displaying colorful scientific images

Dr. Frick’s lab published a new study in Learning and Memory: Frick, Karyn M., Kim, Jaekyoon, Tuscher, Jennifer J., and Fortress, Ashley M. (2015) Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents. Learning and Memory, 22(9):472-493.

Frick-Learning-and-MemoryAmple evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17尾-estradiol (E2), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs.

This review discusses the many ways in which the important sex steroid hormone estradiol regulates memory function in male and female rodents.