Biology subjects

Adelson, P. D.

Publications and source records attributed to Adelson, P. D..

3 recordsLinked to original sources

bioRxiv2023

Aging with TBI vs. Aging: 6-month temporal profiles for neuropathology and astrocyte activation converge in behaviorally relevant thalamocortical circuitry of male and female rats

Traumatic brain injury (TBI) manifests late-onset and persisting clinical symptoms with implications for sex differences and increased risk for the development of age-related neurodegenerative diseases. Few studies have evaluated chronic temporal profiles of neuronal and glial pathology that include sex as a biological variable. After experimental diffuse TBI, late-onset and persisting somatosensory hypersensitivity to whisker stimulation develops at one-month post-injury and persists to at least two months post-injury in male rats, providing an in vivo model to evaluate the temporal profile of pathology responsible for morbidity. Whisker somatosensation is dependent on signaling through the thalamocortical relays of the whisker barrel circuit made up of glutamatergic projections between the ventral posteromedial nucleus of the thalamus (VPM) and primary somatosensory barrel cortex (S1BF) with inhibitory (GABA) innervation from the thalamic reticular nucleus (TRN) to the VPM. To evaluate the temporal profiles of pathology, male and female Sprague Dawley rats (n = 5-6/group) were subjected to sham surgery or midline fluid percussion injury (FPI). At 7-, 56-, and 168-days post-injury (DPI), brains were processed for amino-cupric silver stain and glial fibrillary acidic protein (GFAP) immunoreactivity, where pixel density of staining was quantified to determine the temporal profile of neuropathology and astrocyte activation in the VPM, S1BF, and TRN. FPI induced significant neuropathology in all brain regions at 7 DPI. At 168 DPI, neuropathology remained significantly elevated in the VPM and TRN, but returned to sham levels in the S1BF. GFAP immunoreactivity was increased as a function of FPI and DPI, with an FPI x DPI interaction in all regions and an FPI x Sex interaction in the S1BF. The interactions were driven by increased GFAP immunoreactivity in shams over time in the VPM and TRN. In the S1BF, GFAP immunoreactivity increased at 7 DPI and declined to age-matched sham levels by 168 DPI, while GFAP immunoreactivity in shams significantly increased between 7 and 168 days. The FPI x Sex interaction was driven by an overall greater level of GFAP immunoreactivity in FPI males compared to FPI females. Increased GFAP immunoreactivity was associated with an increased number of GFAP-positive soma, predominantly at 7 DPI. Overall, these findings indicate that FPI, time post-injury, sex, region, and aging with injury differentially contribute to chronic changes in neuronal pathology and astrocyte activation after diffuse brain injury. Thus, our results highlight distinct patterns of pathological alterations associated with the development and persistence of morbidity that supports chronic neuropathology, especially within the thalamus. Further, data indicate a convergence between TBI-induced and age-related pathology where further investigation may reveal a role for divergent astrocytic phenotypes associated with increased risk for neurodegenerative diseases.

neuroscience↗

bioRxiv2021

Dynamic Resting State Motor Network Connectivity of Neurotypical Children, the Groundwork for Network-Guided Therapy in Childhood Movement Disorders

BackgroundNormative childhood motor network resting-state fMRI effective connectivity is undefined, yet necessary for translatable dynamic resting-state network informed treatments in pediatric movement disorders. MethodCross-spectral dynamic causal modelling of resting-state fMRI was investigated in 19 neurotypically developing 5-7-year-old children. Fully connected six-node motor network models were created for each hemisphere including primary motor cortex, striatum, subthalamic nucleus, globus pallidus internus, thalamus, and contralateral cerebellum. Parametric Empirical Bayes with exhaustive Bayesian model reduction and Bayesian modeling averaging were used to create a group model for each hemisphere; Purdue Pegboard Test (PPBT) scores for relevant hand motor behavior were also entered as a covariate at the group level to determine the brain-behavior relationship. ResultsOverall, the resting-state functional MRI effective connectivity of motor cortico-basal ganglia-cerebellar networks was similar across hemispheres, with greater connectivity in the left hemisphere. The motor network effective connectivity relationships between the nodes were consistent and robust across subjects. Additionally, the PPBT score for each hand was positively correlated with the thalamus to contralateral cerebellum connection. DiscussionThe normative effective connectivity from resting-state functional MRI in children largely reflect the direction of inter-nodal signal predicted by other prior modalities and was consistent and robust across subjects, with differences from these prior task-dependent modalities that likely reflect the motor rest-action state during acquisition. Effective connectivity of the motor network was correlated with motor behavior, indicating effective connectivity brain-behavior relationship has physiological meaning in the normally developing. Thus, it may be helpful for future studies in children with movement disorders, wherein comparison to normative effective connectivity will be critical for network-targeted intervention. Impact StatementThis is the first study to use pediatric resting-state functional MRI to create a normative effective connectivity model of the motor network and to also show correlation with behavior, which may have therapeutic implications for children with movement disorders.

neuroscience↗

bioRxiv2019

Diffuse TBI-induced expression of anxiety-like behavior coincides with altered glutamatergic function, TrkB protein levels and region-dependent pathophysiology in amygdala circuitry

Up to 50% of traumatic brain injury (TBI) survivors demonstrate persisting affective symptoms indicative of limbic system dysregulation, yet the pathophysiology underlying the symptoms is unclear. We hypothesize that TBI-induced pathophysiologic changes within distinct amygdala nuclei contribute to the expression of late-onset anxiety-like behavior. Adult, male Sprague-Dawley rats underwent midline fluid percussion injury or sham surgery. Anxiety-like behavior was assessed at 7 and 28 days post-injury (DPI) followed by assessment of real-time glutamate neurotransmission in the basolateral amygdala (BLA) and central nucleus of the amygdala (CeA) using glutamate-selective microelectrode arrays. In separate animal cohorts, the presence of neuropathology, astrocytosis, and microglial activation were assessed at 1, 7, and 28DPI. Protein levels of glutamatergic transporters (Glt-1, GLAST) and presynaptic modulators of glutamate release (mGluR2, TrkB, BDNF, and glucocorticoid receptors) were quantified using automated capillary western techniques at 28DPI. The expression of anxiety-like behavior at 28DPI coincided with decreased glutamate release and slower glutamate clearance in the CeA, not BLA. Changes in glutamate neurotransmission were independent of protein levels of glutamate transporters and mGluR2 receptors, neuropathology, and astrocytosis. At 1DPI, microglia in the CeA demonstrated a neuroinflammatory response. BDNF and TrkB were decreased at 28DPI in the amygdala. These data indicate that diffuse axonal injury instigates sequences of molecular, structural and functional changes in the amygdala that contribute to circuit dysregulation relevant to the expression of affective disorders. Translationally, diffuse axonal injury can influence severity and incidence of affective symptoms and should be addressed in the history of patients with affective disorders.

neuroscience↗