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Background: Epileptic activity is increasingly recognized as a contributor to Alzheimer's Disease (AD) pathology. In AD models, endogenous tau contributes to epileptic activity and associated cognitive deficits through mechanisms that are not fully understood. Increased attention is being directed towards tau's interactions with proteins that regulate neuronal activity, particularly tau's proline rich domain and its binding to SH3‐containing proteins. However, the impact of mutations in tau's proline‐rich region on other protein interactions remains unclear. Method: We assessed mutations in tau's proline rich domain in two mouse lines: AxxA6 (P‐to‐A substitutions in 6th PxxP motif in tau) and R221A (R‐to‐A substitution at amino acid corresponding to 221 in human 2N4R tau). These mutations block tau's interactions with SH3‐containing proteins, including PLCγ1 and p85α/PI3K. Co‐immunoprecipitation (Co‐IP) of tau from cortical brain tissue was confirmed and analyzed by mass spectrometry. We compared protein abundance ratios to wild type tau mice within each mouse line. Significant (p<.05) tau‐baited protein interactions were further explored within literature and the String Database. Result: The R221A line produced 143 and 120 significant proteins within the heterozygous and homozygous groups, respectively. Many identified proteins are strongly associated with processes such as microtubule organization, postsynaptic structure, and mitochondrial functions. The AxxA6 line produced 158 and 126 significant proteins within the heterozygous and homozygous groups, respectively. Many identified proteins are involved in cellular trafficking and are strongly associated with processes such as glutamate catabolic processes and microtubule protein localization. Notably, many proteins identified in both lines are involved in prion disease and vascular endothelial growth factor (VEGF) signaling pathways. Conclusion: Co‐IP mass spectrometry of the R221A and AxxA6 mouse lines revealed that mutations in tau's proline rich domain to affect tau's interactions with multiple proteins. Of the significant proteins, multiple are related to microtubule, metabolic, synaptic, and mitochondrial activity, and many are found within prion disease pathways and VEGF signaling pathways. Interestingly, PLCγ1 and p85α/PI3K, are also implicated in VEGF signaling pathways. These findings highlight the importance of further investigating the possible relationships between noted cellular processes and biological pathways and tau‐protein interactions in familial AD. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) is widely used by researchers to noninvasively monitor brain-wide activity. The traditional assumption of a uniform relationship between neuronal and hemodynamic activity throughout the brain has been increasingly challenged. This relationship is now believed to be impacted by heterogeneously distributed cell types and neurochemical signaling. To date, most cell-type- and neurotransmitter-specific influences on hemodynamics have been examined within the cortex and hippocampus of rodent models, where glutamatergic signaling is prominent. However, neurochemical influences on hemodynamics are relatively unknown in largely GABAergic brain regions such as the rodent caudate putamen (CPu). Given the extensive contribution of CPu function and dysfunction to behavior, and the increasing focus on this region in fMRI studies, improved understanding of CPu hemodynamics could have broad impacts. Here we discuss existing findings on neurochemical contributions to hemodynamics as they may relate to the CPu with special consideration for how these contributions could originate from various cell types and circuits. We hope this review can help inform the direction of future studies as well as interpretation of fMRI findings in the CPu. [ABSTRACT FROM AUTHOR]

Uncommon renal disorders in pregnancy can be challenging to manage given limited evidence in the literature to guide management. We present a series of three uncommon renal disorders in pregnancy: Von Hippel-Lindau disease, Gitelman syndrome, and Nutcracker syndrome. Previously published case reports with differing outcomes offer some guidance to the management of these disorders in pregnancy. In this case series, we address the management of these syndromes during pregnancy and discuss the maternal and fetal outcomes. All three of our patients had good maternal and fetal outcomes, which will contribute to current data on maternal and fetal outcomes in these rare diseases, which is limited. [ABSTRACT FROM AUTHOR]

We sought to compare breast tumor size predicted by imaging modality to the actual pathologic size in order to determine which imaging modality is best at estimating tumor size. We identified 261 patients with biopsy-proven invasive ductal ( IDC) and/or invasive lobular ( ILC) carcinomas with documented tumor dimensions predicted by imaging and maximum dimensions determined by final pathology. Results of imaging-predicted dimension were correlated with final pathological size. Spearman correlations were calculated and compared by Zou's method and agreement was assessed by McNemar's test. There was no significant difference (p > 0.05) between correlations of pathologic size by ultrasound (r = 0.71) and magnetic resonance imaging ( MRI) (0.76). The correlations between MRI or ultrasound and pathologic size are significantly stronger than the correlations between mammography or clinical breast exam and pathologic size (p < 0.05). MRI and ultrasound are both strongly correlated with pathologic size overall and within grades in both IDC and ILC. The correlations between MRI or ultrasound and pathologic size are significantly better than the correlations between mammography or clinical breast exam and pathologic size (p < 0.05). [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation and deep brain stimulation have emerged as therapeutic modalities for treatment refractory depression; however, little remains known regarding the circuitry that mediates the therapeutic effect of these approaches. Here we show that direct optogenetic stimulation of prefrontal cortex (PFC) descending projection neurons in mice engineered to express Chr2 in layer V pyramidal neurons (Thyl-Chr2 mice) models an antidepressant-like effect in mice subjected to a forced-swim test. Furthermore, we show that this PFC stimulation induces a long-lasting suppression of anxiety-like behavior (but not conditioned social avoidance) in socially stressed Thyl-Chr2 mice: an effect that is observed > 10 d after the last stimulation. Finally, we use optogenetic stimulation and multicircuit recording techniques concurrently in Thy 1 -Chr2 mice to demonstrate that activation of cortical projection neurons entrains neural oscillatory activity and drives synchrony across limbic brain areas that regulate affect. Importantly, these neural oscillatory changes directly correlate with the temporally precise activation and suppression of limbic unit activity. Together, our findings show that the direct activation of cortical projection systems is sufficient to modulate activity across networks underlying affective regulation. They also suggest that optogenetic stimulation of cortical projection systems may serve as a viable therapeutic strategy for treating affective disorders. [ABSTRACT FROM AUTHOR]