| الوصف: |
Traumatic brain injury (TBI)-induced disruptions in synaptic function within brain regions and across networks in the limbic system may underlie a vulnerability for maladaptive plasticity and contribute to behavioral comorbidities. In this study we measured how synaptic proteins respond to lateral fluid percussion injury (FPI) brain regions known to regulate emotion and memory, including the basolateral amygdala (BLA), dorsal and ventral hippocampus (DH, VH), and medial prefrontal cortex (PFC). We investigated proteins involved in regulating plasticity, including synaptic glutamatergic a-amino-3-hydroxy5-methyl-4-isoxazolepropionic acid (AMPA; GluA1, GluA2) and N-methyl-D-aspartate (NMDA; NR1, NR2A, NR2B) receptor subunits as well as inhibitory gamma-aminobutyric acid (GABA) synthetic enzymes (GAD67, GAD65) via western blot. Adult male rats received a mild-moderate lateral FPI or sham surgery and ipsi- and contralateral BLA, DH, VH, and PFC were collected 6?h, 24?h, 48?h, and 7 days post-injury. In the ipsilateral BLA, there was a significant decrease in NR1 and GluA2 24?h after injury, whereas NR2A and NR2B were increased in the contralateral BLA at 48?h compared with sham. GAD67 was increased ipsilaterally at 24?h, but decreased contralaterally at 48?h in the BLA. In the DH, both NMDA (NR2A, NR2B) and GABA-synthetic (GAD65, GAD67) proteins were increased acutely at 6?h compared with sham. GAD67 was also robustly increased in the ipsilateral VH at 6?h. In the contralateral VH, NR2A significantly increased between 6?h and 24?h after FPI, whereas GAD65 was decreased across the same time-points in the contralateral VH. In the medial PFC at 24?h we saw bilateral increases in GAD67 and a contralateral decrease in GluA1. Later, there was a significant decrease in GAD67 in contralateral PFC from 48?h to 7 days post-injury. Collectively, these data suggest that lateral FPI causes a dynamic homeostatic response across limbic networks, leading to an imbalance of the proteins involved in plasticity in neural systems underlying cognitive and emotional regulation. |
Full Text Finder