Traumatic brain injury (TBI) impacts 2.5 million people in the U.S. annually. Most people will sustain mild TBI (mTBI). with approximately 13% experiencing chronic cognitive symptoms impacting quality of life. Individuals with mTBI report experiencing sub-clinical deficits in language that include difficulty with starting. maintaining. and following conversations. However. these symptoms are mostly self-reported and elusive using existing clinical tools. Language comprehension demands the efficient construction of a coherent message from a rapid stream of input.

Traumatic brain injury (TBI) and many other brain diseases/injuries exhibit sex differences in prevalence. onset. and outcomes. Some of these differences are attributed to the fact that the human brain is sexually dimorphic and there are certain regional and structural differences that exist between male and female brains. However. the effect of these sex variations in biomechanical responses of brain have not been elucidated. The paucity of sex-specific knowledge in brain biomechanics and TBI fields is mainly due to the fact that. these fields have predominantly focused on males.

The external globus pallidus (GPe) is usually considered simply a relay in the indirect pathway between the striatum and the basal ganglia output neurons in the internal pallidal segment and substantia nigra. This view has been disrupted by recent findings that the GPe contains several different cell types. with different striatal afferents that include the direct pathway. and different downstream targets. and which are interconnected in the GPe by their axon collateral arborizations.

Our goal in this highly collaborative project is to develop compounds to selectively activate the delta opioid receptor (DOR)-kappa opioid receptor (KOR) heteromer allosterically. to promote antinociception effects in vivo and advance lead compounds as possible therapies for pain.Our approach will focus on a DOR/KOR heteromer characteristic known as ???interprotomer allosterism???.

The prevalence of neuropsychiatric disorders is increasing. constituting 28% of the global burden of non-communicable disease. A major cause of these disorders is that of aberrant fetal brain development. and there is growing evidence implicating prenatal exposures as a driving factor. A common exposure that has undergone an exponential increase in incidence during recent years is that of viral infections. due in part to the novel coronavirus disease 2019 (COVID-19) pandemic. Up to 80% of hospitalized COVID-19 patients have manifested neurological complications.

The sense of taste is a complex and integrative chemosensory system that guides consummatory behavior. Taste receptor cells (TRCs) in the taste bud are continuously renewed and must reconnect with peripheral gustatory neurons (GNs) to relay taste signals to the brain1. The turnover and re-establishment of these taste synapses is crucial for the preservation of taste perception over time. In an effort to identify GN-TRC relationships. recent single-cell transcriptomic studies have found genetically distinct subpopulations of geniculate ganglion GNs2. One of these populations.

Learning to avoid stressful events promotes positive mental health outcomes. As such. there is significant interest to identify brain systems that mediate avoidance learning. While the cellular basis of learning has traditionally focused on neurons. accumulating evidence highlights learning depends on astrocyte-neuron interactions. Active avoidance learning depends on ventral tegmental area (VTA) dopamine neurons and their ability to promote active responses during aversive situations. Recent evidence highlights astrocytes in the VTA can modulate dopamine neurons.

The CIDD will continue to provide synthesis support to 4E Therapeutics to prepare and characterize compounds to support the program goals.In our previous work. the synthesis route below has been modified and optimized to address the SAR needs of the 4E program.All novel compounds designed.

The CIDD will continue to provide synthesis support to 4E Therapeutics to prepare and characterize compounds to support the program goals for their GABA-B drug discovery programs.The CIDD will execute synthesis routes to the targeted GABA-B analogs identified by 4E Therapeutics and fully characterize and deliver analogs to 4E Therapeutics for in vitro assessment.The CIDD at UTSA will execute the synthesis routes and prepare the targeted analogs. preparing 10-20 mg of each analog with a targeted purity of >96%.

The Covid-19 pandemic. caused by the virus SARS-Cov2. is the gravest public health crisis in a century. causing over 2.5 million global deaths and enormous human suffering. Along with its signature infection of the respiratory system. are widely seen serious deleterious effects on the brain. Cognitive manifestations of brain infection include delirium. a state characterized by confusion and disorientation. which is prevalent in 70% of Covid-19 patients with severe symptoms and memory deficits. Critically. delirium is often associated with long-term cognitive decline and neurodegeneration.