Biology subjects

Crystal, J. D.

Publications and source records attributed to Crystal, J. D..

3 recordsLinked to original sources

bioRxiv2025

MILD TRAUMATIC BRAIN INJURY IMPAIRS EPISODIC MEMORY IN RATS

Mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury. Symptoms following mTBI fall into physical, emotional, sleep, and cognitive categories, with memory deficits being a commonly documented sequelae. Whereas many animal models of mTBI exist, relatively few studies have examined the cognitive deficits of mTBI with human-like cognitive tasks. The Wayne State University Closed Head Weight Drop Model recapitulates critical physical elements of sport-related concussions and trauma-based mTBI. However, until now, this model has not previously been evaluated using a human-like memory task. Rats were trained in an odor-based item-in-context task that dissociates episodic and non-episodic memory (Panoz-Brown et al., Current Biology, 2016). The animals then underwent either a weight drop or a sham procedure. After the manipulation, animals were assessed in the item-in-context task. Episodic memory was significantly impaired in the injured rats by over 10% but not in the sham rats. Non-episodic memory was not impaired in either group. Additionally, a time-course immunohistochemical analysis of the hippocampus was performed to examine possible time-dependent changes in ionized calcium-binding adaptor molecule 1 (iba1), a marker of activated microglia/macrophages and glial fibrillary acidic protein (GFAP), a marker of astrocytes. Concussion injury was associated with time-dependent morphological changes in astrocytes and microglia in injured rats compared to sham rats. This study is the first to document episodic memory impairment in an animal model of mTBI.

neuroscience↗

bioRxiv2025

MILD TRAUMATIC BRAIN INJURY IMPAIRS SPATIAL WORKING MEMORY IN RATS

Mild Traumatic Brain Injury (mTBI), or concussion, is the most common form of traumatic brain injury, which accounts for about 80% of cases. It is a common problem in contact sports and may lead to cognitive impairment. This study used the Wayne State University closed-head weight-drop model in lightly anesthetized and unrestrained Long Evans rats. This model allows for the rapid acceleration and deceleration of the head and torso, similar to the biomechanics in human mTBI. Rats were administered a single weight drop. Sham animals were treated the same as the mTBI group but were not subjected to weight drop. Rats were trained in an 8-arm radial maze to assess spatial working memory before and after weight drop manipulation. We observed that the injured rats spatial working memory performance significantly declined compared to the sham rats (cohens d = 1.88). Specifically, the performance of the sham group continued to improve after the sham procedure, whereas the performance of the injury group decreased. This study suggests the WDM model produces a deficit in spatial working memory in rats.

animal behavior and cognition↗

bioRxiv2024

Negative allosteric modulation of CB1 cannabinoid receptor signaling decreases intravenous morphine self-administration and relapse in mice

The endocannabinoid system interacts with the reward system to modulate responsiveness to natural reinforcers, as well as drugs of abuse. Previous preclinical studies suggested that direct blockade of CB1 cannabinoid receptors (CB1R) could be leveraged as a potential pharmacological approach to treat substance use disorder, but this strategy failed during clinical trials due to severe psychiatric side effects. Alternative strategies have emerged to circumvent the side effects of direct CB1 binding through the development of allosteric modulators. We hypothesized that pharmacological inhibition of CB1R signaling through negative allosteric modulation (NAM) would reduce the reinforcing properties of morphine and decrease opioid addictive behaviors. By employing i.v. self-administration in mice, we studied the effects of the CB1-biased NAM GAT358 on morphine intake, relapse-like behavior, and motivation to work for morphine infusions. Our data revealed that GAT358 reduced morphine infusion intake during the maintenance phase of morphine self-administration under fixed ratio 1 schedule of reinforcement. GAT358 decreased morphine-seeking behavior after forced abstinence. Moreover, GAT358 dose-dependently decreased the motivation to obtain morphine infusions in a progressive ratio schedule of reinforcement. Strikingly, GAT358 did not affect the motivation to work for food rewards in an identical progressive ratio task, suggesting that the effect of GAT358 in decreasing opioid self-administration is reward specific. Furthermore, GAT58 did not produce motor ataxia in the rota-rod test. Our results suggest that CB1R NAMs reduced the reinforcing properties of morphine and could represent a viable therapeutic route to safely decrease opioid-addicted behaviors.

animal behavior and cognition↗